Trajectory of skill acquisition, loss, and regain in females with classic Rett syndrome

Trajectory of skill acquisition, loss, and regain in females with classic Rett syndrome | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Trajectory of skill acquisition, loss, and regain in females with classic Rett syndrome Jeffrey L. Neul, Timothy A. Benke, Eric D. Marsh, Sarika U. Peters, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8245192/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 12 Mar, 2026 Read the published version in Journal of Neurodevelopmental Disorders → Version 1 posted 9 You are reading this latest preprint version Abstract Background To characterize frequency, timing, and trajectory of gain, loss, and regain of developmental skills in Classic Rett syndrome (RTT). Methods The frequency and timing of gain, loss, and regain of 51 developmental skills from 1228 females with Classic RTT and a pathogenic loss-of-function variant in MECP2 was assessed during in-person visits from participants enrolled in the US Natural History Study. The percentage of participants experiencing gain, loss, or regain events, mean and median age of event and time to event with confidence intervals, and the cumulative incidence curves were calculated and compared to normative data using SPSS v29.0.2.0. One-year incidence of either gain or regain of each skill from 0–20 years old and one-year incidence of either gain or regain of any of 51 developmental skills was calculated. Results The acquisition of skills was greatest for lower-level skills and conversely lowest for more advanced skills. Acquisition of skills peaked at 6 years. Skill loss occurred mainly within 2 years of acquisition. Loss of fine motor, communication, and social adaptive skills changed little after age 6 years. The regain of lost skills involved less than 30% of fine motor, communication, and social adaptation. Regain of skills generally ceased by age 6 years. Conclusion These results provide critical endpoints essential for conducting clinical trials in RTT. The lack of acquisition of skills beyond age 6 years and absence of loss or regain of previously lost skills, aside from gross motor features, beyond 6 years suggest that functional gains in these realms would represent important indicators of efficacy. Rett syndrome Developmental milestones Gain/Loss/Regain Natural History Study Clinical trial endpoint Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Rett syndrome (RTT) is a rare neurodevelopmental disorder primarily caused by pathogenic variants in Methyl-CpG-Binding Protein 2 ( MECP2 ) [ 1 , 2 ]. RTT primarily, but not exclusively, affects females [ 3 , 4 ] and has a characteristic disease pattern with “normal” initial development, followed by developmental delay and then regression with loss of hand skills and spoken language, gait problems, and hand stereotypies [ 5 , 6 ]. After regression, a “Pseudostationary” stage occurs that has been characterized by no further skill loss and potential skill regain [ 7 , 8 ]. Eventually, a “Late Motor Decline” stage occurs, characterized by muscular rigidity, declining gross motor ability, and onset of Parkinsonian features [ 7 , 9 – 11 ]. Although previous work has described aspects of the gain and loss of developmental skills (also referred to as “developmental milestones”) [ 12 – 15 ], data on the frequency and timing of skill gain and loss remains incomplete, and evaluation of skill regain is minimally characterized. The need for this information is driven by the demonstration that restoration of MeCP2 function, even after symptom onset, can reverse phenotypic problems in RTT mouse models [ 16 , 17 ]. This provided the foundation for disease modifying therapy development, such as gene therapy clinical trials for RTT [ 18 ]. Transformative therapies for RTT should change the course of the disease by enabling the acquisition of new skills, restoring lost skills, or preventing skill loss. Therefore, it is critical to understand the expected trajectory of skill gain, loss, and regain in RTT to objectively evaluate the therapeutic impact of novel therapies compared to historical data. From 2006–2021, the multi-site US Rett syndrome and Rett-related disorders Natural History Study (RNHS) longitudinally evaluated a large number of people with RTT [ 19 ], providing information on the clinical features and disease progression of RTT [ 20 – 28 ], identifying and evaluating putative biomarkers [ 29 – 33 ], developing outcome measures [ 34 – 40 ], and establishing a clinical research network to enable the development of the first FDA-approved treatment for RTT [ 41 ]. The RNHS captured information on developmental skill gain, loss, and regain from people with RTT, and analysis of early data from the RNHS provided information about developmental skill gain and loss [ 13 ]. However, this previous work was limited by a smaller sample size and data on fewer skills compared with information available after the RNHS completion. Further, the previous work focused on skill gain or loss and did not evaluate skill regain or the incidence of skill gain or regain within a clinical trial timeframe. To address this need, we characterized the frequency and timing of skill gain, loss, and regain in females with Classic RTT and a pathogenic variant in MECP2 using the extensive RNHS dataset. We evaluated the time from gain to loss and the time from loss to regain to understand the temporal relationship between events. Further, we characterized the fraction of participants who gained a skill beyond either 4 or 6 years old, regained a skill beyond 6 years old or more than 2 years after loss, as well as determining the one-year incidence of gaining or regaining a skill. This work provides detailed information on the trajectory of developmental skill gain, loss, and regain in RTT to facilitate earlier diagnosis, guide clinical management, and establish foundational information relevant to the evaluation of disease modifying therapies for RTT. Methods Participants Participants were enrolled in the Rett syndrome and RTT-related Disorders Natural History Study (RNHS, NCT00299312, NCT02738281), a longitudinal study incorporating caregiver-provided historical and clinically observed information spanning from 2006 to 2021 [ 19 ]. Participants were included in the RNHS if they had a clinical diagnosis of RTT based on the clinical consensus criteria [ 6 ], had a pathogenic variant in MECP2 but did not meet RTT clinical diagnostic criteria, or had a diagnosis of a RTT-related disorder ( MECP2 duplication syndrome, CDKL5 deficiency disorder, or FOXG1 syndrome). Participants enrolled provided genetic testing results, although not all enrolled participants had an identified pathogenic genetic variant. All participants or their legally authorized representatives provided informed consent before participation in the RNHS. The RNHS was conducted in accordance with the Declaration of Helsinki, and approved by the University of Alabama, Birmingham Institutional Review Board. A Certificate of Confidentiality was provided by the National Institute of Child Health and Development (NICHD). Overall, 1826 individuals participated in the RNHS with an average of ~ 5 visits per individual. For this study, we restricted analyses to female participants diagnosed with Classic RTT with a pathogenic variant in MECP2 who had some data collected on developmental milestone skill gain, loss, or regain (N = 1228). The mean age of first visit for this cohort was 11.7 years (Standard Error of the Mean [SEM] = 0.28 years), with a median age of enrollment of 8.2 years (Interquartile Range [IQR] = 4.2–16.4 years). The median number of study visits was 5 (range: 1–17; IQR: 2–8). The majority (71.3%) were white and not Hispanic (see Additional file 1: Table S1 Demographic Information for complete demographic information). Additional file 2: Table S2 MECP2 Mutation Frequency displays the breakdown of the frequency of common MECP2 point mutations and other mutation groups in the analysis cohort. For MECP2 mutation groups, we grouped rare point mutations affecting the same amino acid codon as common recurrent point mutations into the common point mutations. Specifically, participants with R106Q variants were grouped with R106W; those with R133P or R134C variants were grouped with R133C; participants with T158A or T158P were grouped with T158M, and participants with R306H or R306L were grouped with R306C. The Early Truncations group included all nonsense of frameshift variants before position R270, including splice site variants, but excluding the common recurrent nonsense point variants (R168X, R255X, R270X). The C-terminal Truncations group included all frameshift or nonsense variants after position R270, excluding the common recurrent nonsense point mutation R294X. Other point mutations encompass all other missense variants aside from the common recurrent variants (R106W, R133C, T158M, R306C). This approach to grouping pathogenic genetic variants is consistent with previous work [ 42 , 43 ]. Visit Schedule and Assessments Participants were assessed in a structured in-person clinical research visit (lasting ~ 1–2 hours), which occurred longitudinally at pre-defined intervals based on age of enrollment, ranging from twice per year to every other year [ 19 ]. In-person evaluations utilizing structured research forms including caregiver completed history and assessment forms and questionnaires, clinical histories, structured clinical exams, and clinician-completed rating scales. Information on the gain, loss, and regain of developmental skills was captured through a detailed, direct interview with caregivers. Caregivers were provided a developmental skill history questionnaire prior to the baseline visit and asked to provide information on whether a specified skill was gained, lost, or regained and the age of gain, loss, or regain (or indicate age of skill event being unknown). Caregivers were instructed to review and refer to aids to improve recall such as baby books and pictures, and review of prior medical evaluations by primary care physicians and any subspecialists. During the in-person baseline visit, the developmental skill history questionnaire was reviewed by the clinical investigator with the caregiver to discuss and confirm the answers provided by the caregiver, as well as raise questions about the caregiver’s responses with regards to the current ability of the participant ( e.g. if caregiver stated that the participant had gained but not lost a skill, but the participant was not able to perform the skill during the clinical evaluation or by parent report, the investigator would ask for clarification of the developmental history report provided that indicated that the skill was not lost). At all subsequent visits, the developmental history log was reviewed with the caregiver to assess whether any changes occurred since the previous study visit with regards to skills being gained, lost, or regained and updates to the form made to reflect these changes. From 2006–2014, the developmental skill history questionnaire queried 31 developmental skills (NCT00299312, RNHS protocol 5201). In 2015, upon initiation of the third funding cycle, the data capture forms underwent a major revision including modification of the developmental skill history questionnaire (NCT02738281, RNHS protocol 5211), which added a number of new developmental skills to expand the range and detail of developmental milestones assessed and dropped three skills captured in the previous protocol (Roll Back to Front, Pedal Tricycle, and Stopped Being Visually Attentive) based on analysis showing either floor or ceiling effects for these three skills. The new developmental skill history questionnaire included a total of 51 developmental skills, with 28 mapping to skills captured in 5201 and the addition of 23 additional skills. The names of the skills in both protocols, the mapping of the skills between the two protocols, and the names used for the skills in this paper are provided in Additional file 3: Table S3 Developmental skill mapping between protocols 5201 and 5211 . For this study, we analyzed the 51 skills assessed in protocol 5211 (2015–2021) and merged the information from the two protocols as shown in Additional file 3: Table S3 Developmental skill mapping between protocols 5201 and 5211 . For participants meeting the inclusion criteria for these analyses defined above (N = 1228), 586 participated solely in 5201, 307 participated only in 5211, and 335 participated in both 5201 and 5211. For participants evaluated in both 5201 and 5211, initial age of skill events provided were used in cases when there were discrepancies between dates identified between data collected in the two protocols; however, updated information collected during 5211 reflecting changes in skill event occurrence from 5201 were used to reflect changes in skill gain, loss, or regain over time. Total Ns (Tables 1 – 3 ) reflect total number of participants from 5201 and or 5211 with information available on skill gain, loss, or regain post data processing and cleaning described below. The calculation of the mean and median age of skill gain, loss, or regain was based only data for which a specific age of event was obtained (excluding those participants with an "age unknown" indicator), thus the total number of participants included in these calculations are lower than the total number with data indicating whether the skill event occurred or did not occur. Data processing and cleaning prior to analyses Prior to analysis, the raw data went through a series of processing and data cleaning steps. Prior to data cleaning, data fields coded as “Yes” or “No” were recoded as “1” or “0”. The full description of the cleaning process criteria is provided in Additional file 4: Supplemental Methods , including the number of changes (n) made according to each criterion. Overall, this process resulted in changes to 26,170 data cells, which represents changes to 4.64% of all data cells. The changes fell into the following broad categories: Most changes were to skill event occurrence indicators (n = 23,575; 4.22%), with the vast majority of these removing subsequent skill event indicator of “No” when preceding skill event did not occur (n = 22,537, 4.0%). The remaining changes to skill event occurrence indicators (n = 1,221; 0.22%) added missing skill event indicators to subsequent skill events when preceding skill event occurred, correcting preceding skill event indicators when subsequent skill occurred, or adding missing skill event occurrence indicator when age of skill event was provided or age of skill event was indicated as “unknown”. The next largest group of changes were corrections to age of skill event unknown indicators to remove the age of skill event unknown indicator if the age of skill event was provided, or add skill event unknown indicator when event occurred but the age of skill event was not entered and the age of skill event unknown indicator was blank (n = 1,205, 0.2%) Correcting logical age inconsistencies ( e.g. the age of skill event entered was beyond the age of last visit or before the preceding skill event age) was the next largest group of changes (n = 736, 0.13%) Identifying entries for the age of skill gain that was at an unrealistically young age of gain and removing age of gain and adding age of gain unknown indicator was the next largest group of changes (n = 590, 0.1%) Finally, the smallest group of changes were based on review of source data (n = 64, 0.01%) After cleaning, all ages were converted from “months” to “years” (with 1 decimal point) by dividing months by 12. For all skill events that were identified as not having occurred (and not blank), the age of last visit (in years) was inserted into the age of event field as “censored age” data for subsequent survival analysis. Statistical Analyses and Data Visualization All data was stored and processed in Excel v16 (Microsoft). The presentation of the data for this study is descriptive; no hypothesis tests were performed. SPSS v29.0.2.0 (IBM, Armon, NY, USA) was used to calculate proportions, mean values with standard error of the mean (SEM), median values, and Kaplan-Meyer (cumulative incidence) survival tables. The overall rate of gain, loss, or regain for each skill for all cases with information on the status of the event (including those without information on the age of the event) was calculated as the proportion (presented as percentage) of individuals in which the event occurred over all individuals with information for that skill event. Because the denominator varies across skill events, the raw number for the numerator (individuals in which the skill event occurred) and the denominator is presented. Confidence Intervals (95%) for skill event proportions were calculated using the BINOMIAL function in SPSS using Likelihood (normal approximation) unless the number of individuals in which an event occurred [n(p)] or did not occur [n(1-p)] was less than 5, or if the proportion of occurrence (p) or non-occurrence (1-p) was less than 0.10, in which the Clopper-Pearson exact method was used. Mean and median age of event was calculated using only individuals with available information as no imputation was performed. Median skill event age and age range (5–95%) was calculated using the ROUND function in SPSS. Cumulative incidence tables were calculated using Kaplan-Meyer survival analysis, with censoring if the skill event did not occur. The age of last visit was used for the censored age for skill gain, loss, or regain. For time from gain to loss or time from loss to regain, the censored age was the age of last visit minus the age of the preceding skill event. The cumulative incidence tables were used to calculate the percent of individuals who gained a skill beyond 4 years or 6 years of age, regained a skill beyond 6 years of age, or regained a skill more than 2 years after losing that skill. Additionally, we used these cumulative incidence tables to determine the percentage of individuals who did not gain a skill by the age the US Centers for Disease Control (CDC) indicates that most children (75% based on normative data) are expected to achieve that skill [44]. This calculation was only done for those skills for which CDC normative age recommendations for surveillance are available (41 of the 51 skills assessed in this study). Graphical representation of cumulative incidence curves (survival or 1-survival curves) was generated using R v4.5 (www.r-project.org), with Powerpoint v16.1 (Microsoft) used to create merged figures of representative cumulative incidence curves. The incidence of either gaining or regaining a skill during a one-year interval was calculated for one-year bins from 0–20 years of age. For the analysis of one-year interval incidence, information of gain or regain of skills beyond 20 years of age was not included. To determine the one-year incidence of gain or regain for each skill, the number of individuals who gained or regained that skill within the one-year interval was divided by the total number of individuals eligible to either gain or regain the skill during the specified interval. The detailed logic used to determine skill gain or regain and eligibility in each interval is provided in the Additional file 4: Supplemental Methods . For each individual, the total number of skills gained or regained in each one-year interval was calculated, and the percentage of individuals who gained at least 1 of 51 or 1 of the 38 skills selected (described in the results section) was determined by dividing by the total number of participants eligible to gain or regain a skill in that interval. Results Developmental Skill Gain Delayed or absent acquisition of developmental skills is a well-recognized feature in RTT [ 12 – 15 ]. The percentage of participants in this study who gained specific developmental skills ranged from 99.5% for Social Smile to 2.4% for Shared Stories (Table 1 ). Across developmental skill domains (gross motor, fine motor, receptive language, expressive language, social/adaptive skills), the frequency of skill gain was highest for lower level and earlier acquired skills than for more advanced skills. For example, within the gross motor skill domain, nearly 100% of participants gained early skills such as lifting head, rolling from tummy, and sitting with or without support, but only ~ 60% gained the ability to walk independently (Table 1 ). Similarly, within expressive language, nearly all participants gained early skills such as Cooing and Babbling, but less than 25% gained Spoken Phrases. Out of the 51 skills characterized, 21 individual skills were gained by over 80% of all participants and only 2 skills were gained by less than 20% of all participants (Down Stairs Without Help and Shared Stories). In the participants that age of skill gain was known, the mean age of skill gain (Table 1 ) ranged from 0.2 years (Like Being Held) to 6.9 years (Shared Stories), and the median ages of skill gain ranged from 0.1 years (Like Being Held) to 3 years (Point to 1 Color). Examples of cumulative incidence curves (Kaplan-Meyer 1-Survival curves) for the gain of representative developmental skills are shown in Fig. 1 , with curves for all developmental skills provided in Additional file 5: Figure S1 . The median age of skill gain was one year or younger for 33 of the 51 skills (65%), and two years or younger for 50 skills (98%) (Table 1 ). For 26 of the 51 developmental skills (51%), 95% of participants who gained that skill did so by 2 years old (Table 1 ). By 4 years of age, this increased to 73% of the skills (37 of 51 skills), and by 6 years old it increased to 92% of the skills (47 of 51 skills). For each developmental skill, we calculated the percentage of participants who gained the skill after age 4 or 6 years of age (Table 1 ). The percentage of participants who gained a specific skill after 4 years of age was less than 5% for all skills except Point to 1 Color. The percentage of participants who gained a specific skill after 6 years of age was less than 2.5% for 50 of the 51 skills, with the majority (35 of 51) of the skills being gained by 1% or less of participants who gained the skill. These data demonstrate that acquisition of the skills evaluated in this study generally occurs early in life in people with RTT, with the majority (95%) of people who gain a specific skill doing so before 4 years of life, and 97.5–99% who gain a specific skill doing so before 6 years of life. The US Centers for Disease Control (CDC) has developed normative guidelines for developmental surveillance based on the age that most ( > = 75%) of children should attain specific developmental skills to help with early identification of children with developmental delays or disabilities [ 44 ] ( https://www.cdc.gov/act-early/index.html ). Of the 51 developmental skills evaluated in this study, CDC age-specific surveillance recommendations are available for 41 skills. We characterized the percentage of participants in this study who had not yet gained a specific skill by these CDC recommendations (Table 1 ). The percentage of participants who did not gain a skill by the CDC guidelines ranged from 14.6% (Sit Without Support) to 99.5% (Shared Stories). Notably, in 26 of the 41 (63.4%) skills with CDC recommended age of gain, the majority (> 50%) of study participants did not gain the skill by the CDC threshold age. For advanced skills such as Shared Stories, the age that most children are expected to gain the skill is beyond the typical age of regression in RTT (~ 18 months [ 12 , 45 ]). However, it is notable that a significant percentage of participants fail to acquire lower-level skills that are expected to be gained before 6 months of life, such as Lift Head (59.3%), Hold Bottle (84.8%), Social Smile (45.9%), and Eyes Fix and Follow (70.2%). Furthermore, a significant percentage also failed to gain major milestones that are expected to be gained by 18 months of life (1.5 years) such as Pull to Stand (62.1%), Walk Independently (66.8%), Pincer Grasp (41.6%), Words with Meaning (45.8%), and Point for Wants (84.2%). As the average age of diagnosis of RTT is 2.7 years [ 46 ], these notable early departures from expected age of gain of developmental skills should raise concerns for caregivers and primary care providers. Table 1 Developmental Skill Gain . Skill Gain All Cases Age Gain (yr) % Not Gained by % Gain Beyond Age Total N % Gain (95% CI, N) Mean (SEM, N) Median (5%, 95%) CDC (yr) > 4yo ( N ) > 6yo ( N ) Gross Motor Lift Head 636 98.1 (96.7–99.0, 624)* 0.3 (0.02, 315) 0.3 (0.1, 0.8) 59.3 (0.2) 0.3 (1) 0.0 (0) Roll From Tummy 1224 96.0 (94.7–97.0, 1175)* 0.5 (0.01, 983) 0.4 (0.2, 0.9) 25.9 (0.5) 0.0 (0) 0.0 (0) Sit With Support 637 98.6 (97.3–99.4, 628)* 0.6 (0.02, 494) 0.5 (0.3, 0.9) 36.8 (0.5) 0.2 (1) 0.0 (0) Sit Without Support 1227 97.1 (96.0-97.9, 1191)* 0.7 (0.01, 1050) 0.6 (0.3, 1.2) 14.6 (0.8) 0.4 (3) 0.3 (2) Come To Sit 1227 83.0 (80.8–85.0, 1018) 0.9 (0.02, 843) 0.8 (0.4, 1.8) 45.1 (0.8) 0.3 (2) 0.1 (1) Crawl 1225 70.9 (68.3–73.4, 868) 1.0 (0.02, 785) 0.9 (0.5, 1.8) N/A 0.3 (3) 0.0 (0) Stand With Support 633 85.6 (82.7–88.2, 542) 1.1 (0.03, 371) 1.0 (0.7, 2.0) N/A 0.8 (3) 0.0 (0) Pull To Stand 1228 67.7 (65-70.2, 831) 1.1 (0.02, 724) 1.0 (0.6, 2.0) 62.1 (1.0) 0.1 (1) 0.1 (1) Walk With Support 1226 79.0 (76.7–81.3, 969) 1.4 (0.03, 850) 1.1 (0.8, 2.7) 66.6 (1.0) 1.4 (12) 0.3 (2) Stand Independently 635 64.7 (61-68.4, 411) 1.6 (0.1, 261) 1.4 (0.8, 3.5) N/A 1.7 (7) 0.5 (2) Walk Independently 1227 59.3 (56.5–62.0, 727) 1.7 (0.04, 695) 1.5 (1.0, 3.3) 66.8 (1.5) 1.8 (17) 1.0 (8) Ran 10 Feet 638 29.5 (26.0-33.1, 188) 1.9 (0.1, 99) 1.6 (1.1, 3.9) 86.5 (2.0) 0.5 (2) 0.5 (2) Up Stairs With Help 636 53.9 (50.0-57.8, 343) 2.4 (0.1, 194) 2.0 (1.0, 5.0) N/A 4.2 (17) 1.4 (5) Up Stairs WO Help 1226 25.9 (23.5–28.4, 318) 2.3 (0.1, 235) 2.0 (1.0, 5.0) 87 (2.0) 1.9 (18) 0.5 (4) Down Stairs With Help 637 44.0 (40.1–47.8, 280) 2.7 (0.1, 147) 2.0 (1.0, 6.0) N/A 4.1 (16) 1.8 (6) Down Stairs WO Help 1227 19.6 (17.5–21.9, 241) 2.7 (0.2, 173) 2.0 (1.0, 6.0) N/A 2.1 (17) 1.3 (9) Fine Motor Hold Bottle 1226 88.9 (87.1–90.6, 1090) 0.7 (0.01, 889) 0.6 (0.3, 1.3) 84.8 (0.3) 0.1 (1) 0.0 (0) Reach For Toy 1226 97.6 (96.7–98.4, 1197) 0.6 (0.02, 934) 0.4 (0.2, 1.2) 32.2 (0.5) 0.4 (3) 0.3 (2) Raking Grasp 636 89.8 (87.3–92.0, 571) 0.8 (0.1, 278) 0.6 (0.3, 2.0) 37 (0.8) 1.2 (3) 0.9 (2) Transfer Objects 1226 76.8 (74.4–79.1, 942) 0.8 (0.03, 653) 0.7 (0.3, 2.0) 50.5 (0.8) 0.3 (2) 0.2 (1) Pincer Grasp 1226 76.8 (74.3–79.1, 941) 1.0 (0.03, 708) 0.8 (0.5, 2.0) 41.6 (1.0) 0.9 (7) 0.4 (2) Finger Feeding 1227 92.1 (90.4–93.5, 1130)* 0.9 (0.02, 915) 0.8 (0.5, 1.5) 16.7 (1.3) 0.4 (3) 0.2 (1) Turn Pages in Book 636 56.0 (52.1–59.8, 356) 1.2 (0.1, 196) 1.0 (0.6, 2.5) 60.3 (2.5) 0.5 (2) 0.3 (1) Expressive Social Smile 1225 99.5 (98.9–99.8, 1219)* 0.3 (0.01, 991) 0.2 (0.1, 0.8) 45.9 (0.2) 0.0 (0) 0.0 (0) Cooing 1225 94.1 (92.7–95.4, 1153)* 0.3 (0.01, 861) 0.3 (0.1, 0.8) 24.4 (0.3) 0.1 (1) 0.0 (0) Babbling 1224 95.3 (94.0-96.5, 1167)* 0.7 (0.02, 898) 0.5 (0.3, 1.3) 22.2 (0.8) 0.4 (3) 0.1 (1) Words With Meaning 1226 76.7 (74.3–79.0, 940) 1.1 (0.02, 782) 1.0 (0.5, 2.0) 45.8 (1.0) 0.6 (5) 0.1 (1) Spoken Phrases 1223 23.5 (21.1–25.9, 287) 2.0 (0.1, 196) 1.5 (1.0, 4.0) 86.9 (2.0) 2.0 (11) 1.4 (5) Wave Bye 1224 58.5 (55.7–61.2, 716) 1.1 (0.1, 551) 0.8 (0.5, 2.6) 58.9 (1.0) 1.5 (10) 0.9 (5) Point for Wants 1222 30.5 (28.0-33.1, 373) 1.7 (0.1, 265) 1.0 (0.5, 4.4) 84.2 (1.3) 2.2 (14) 1.6 (8) Shared Stories 636 2.4 (1.4–3.7, 15) 6.9 (3.1, 6) 2.0 (1.3, 21) 99.5 (4.0) 1.0 (3) 0.9 (2) Receptive Quiet To Voice 1223 90.0 (88.2–91.6, 1101)* 0.4 (0.03, 724) 0.2 (0.0, 1.5) 49.4 (0.2) 1.2 (4) 0.6 (3) Respond To Sounds 637 97.5 (96.0-98.6, 621)* 0.3 (0.03, 311) 0.2 (0.0, 0.8) 39.6 (0.2) 0.3 (1) 0.0 (0) Play Peek-A-Boo 633 62.6 (58.7–66.3, 396) 0.7 (0.04, 181) 0.6 (0.3, 1.5) 66.5 (0.8) 0.0 (0) 0.0 (0) Respond To Words 636 91.7 (89.4–93.6, 583) 0.9 (0.1, 254) 0.7 (0.3, 2.0) N/A 1.3 (2) 1.3 (2) Respond To Own Name 637 96.2 (94.6–97.5, 613) 1.0 (0.1, 257) 0.7 (0.3, 3.0) 40.2 (0.8) 2.4 (4) 1.6 (2) Inhibit To No 1225 72.4 (69.9–74.9, 887) 1.4 (0.1, 558) 1.0 (0.5, 3.5) 60.3 (1.0) 1.9 (13) 1.3 (8) Commands With Gesture 1220 59.6 (56.8–62.3, 727) 1.8 (0.1, 460) 1.1 (0.5, 5.0) 71.7 (1.3) 4.5 (32) 2.2 (13) Commands WO Gesture 1225 48.5 (45.7–51.3, 594) 2.0 (0.1, 366) 1.3 (0.7, 6.0) 77.7 (1.5) 4.6 (31) 2.4 (12) Identify Body Parts 634 41.8 (38.0-45.7, 265) 2.4 (0.2, 120) 1.5 (0.8, 6.0) 82.4 (2.0) 3.2 (11) 2.0 (6) Point to 1 Color 635 46.9 (43.1–50.8, 298) 3.9 (0.3, 134) 3.0 (1.0, 10.0) 88.1 (2.5) 12.3 (43) 7.3 (22) Social/Adaptive Like Being Held 1223 96.0 (94.7–97.0, 1174)* 0.2 (0.02, 880) 0.1 (0.0, 0.7) N/A 0.2 (2) 0.1 (1) Attention to Sounds 634 89.4 (86.9–91.7, 567) 0.5 (0.1, 240) 0.3 (0.0, 1.3) 68.1 (0.2) 0.7 (2) 0.7 (2) Eyes Fix and Follow 1221 95.1 (93.8–96.2, 1161) 0.5 (0.04, 749) 0.3 (0.1, 1.8) 70.2 (0.2) 1.4 (8) 1.1 (6) Play Pat-A-Cake 633 28.1 (24.7–31.7, 178) 0.8 (0.05, 83) 0.8 (0.5, 1.6) 86.8 (1.0) 0.0 (0) 0.0 (0) Desire Social Attention 632 84.8 (81.9–87.5, 536) 0.8 (0.1, 232) 0.3 (0.0, 3.0) N/A 1.9 (4) 0.9 (1) Imitate Peers 629 21.3 (18.2–24.6, 134) 2.2 (0.4, 58) 1.1 (0.7, 6.0) 94.2 (1.3) 1.6 (6) 1.0 (3) Been Independent 630 35.6 (31.9–39.3, 224) 2.4 (0.3, 96) 1.3 (0.8, 8.0) N/A 2.8 (9) 2.1 (5) Drinks WO Help 636 61.5 (57.7–65.2, 391) 1.2 (0.1, 199) 1.0 (0.5, 2.5) 61.7 (1.5) 1.4 (5) 0.4 (1) Uses Utensils With Help 636 67.5 (63.7–71.0, 429) 1.8 (0.1, 215) 1.2 (0.7, 5.0) 64.5 (1.5) 3.6 (13) 1.3 (4) Uses Utensils WO Help 636 26.6 (23.2–30.1, 169) 2.3 (0.3, 76) 1.3 (0.8, 8.0) 88.4 (2.0) 2.3 (8) 1.9 (6) Table 1 Legend : The first column in the table displays the total number (N) for all cases with information available whether the specific developmental skill was gained or not. The second column shows the percentage (%), 95% Confidence Interval (CI) and number of individuals (N) who gained each skill. * Indicates where the Clopper-Pearson exact method was used to calculate the CI. The third and fourth columns present the age of skill gain in years (yr) and the standard error of the mean (SEM) for cases with a known age of gain (N), and the median age of skill gain with 5–95% intervals yrs). The fifth column shows the percent of individuals who did not gain a specific skill by the CDC defined age threshold (displayed in parentheses). N/A indicates that no normative CDC threshold is available for that particular skill. Finally, the percentage of individuals who gain the skill beyond either 4 years old (yo) or 6 years old (yo) is displayed in the last two columns, including the total number (N) who gained the skill beyond the specific age cutoff. Skill domains are demarked on left side. Expressive Communication is labeled “Expressive” and Receptive Communication is labeled “Receptive”. Developmental skill loss Regression, or loss of previously acquired developmental skills, is a defining characteristic of RTT [ 5 , 6 ]. Therefore, we calculated the percentage of participants who lost specific skills previously gained, as well as the mean and median age of skill loss (Table 2 ). The percentage of participants who lost previously gained skills ranged from 6.6% (Lift Head) to 88.6% (Words with Meaning). The high frequency of loss of Fine Motor and Expressive Language skills is consistent with regression in these domains being a conditio sine qua non of RTT [ 15 ]. However, Gross Motor, Receptive Language, and Social/Adaptive skills are also lost in a significant fraction of people with RTT. The mean age of skill loss ranged from 1.6 years old (Cooing, Respond to Sounds) to 8.2 years old (Down Stairs With Help), and the median age of loss ranged from 1.3 years old (Cooing) to 7.3 years old (Down Stairs With Help). The median age of skill loss was 3 years old or less for 46 of the 51 developmental skills (90%), and in 31 developmental skills, 95% of participants lost skills by 6 years old. Cumulative incidence curves (Kaplan-Meyer Survival curves) of loss of representative developmental skills are shown in Fig. 2 (Panels A1, B1, C1, D1, E1), with loss curves for all developmental skills provided in Additional file 6: Figure S2 . Notably, while most skill domains show a relatively tight window of loss across all participants, the loss of Gross Motor domain skills such as Stand Independently or Walk Independently occurs more gradually and over a longer time period (Table 2 and Fig. 2 A1 ). Given the variation in the age of skill gain, we calculated the time from gain to loss for all developmental skills (Table 2 ) . The mean time from gain to loss ranged from 0.7 years (Point to 1 Color) to 6.6 years (Stand Independently), and the median time from gain to loss ranged from 0.5 years (Words With Meaning, Spoken Phrases) to 5.3 years (Stand Independently). Overall, the median time from gain to loss was less than 2 years for 44 of the 51 developmental skills (86.3%). Consistent with the analysis of the age of loss, the skills that had median time from gain to loss greater than 2 years were all within the gross motor domain such as Stand Independently (5.3 years), Walk Independently (4.0 years), or Down Stairs With Help (5.0 years). Figure 2 (Panels A2, B2, C2, D2, E2) shows cumulative incidence curves for the time from gain to loss for representative developmental skills, with gain to loss cumulative incidence curves for all developmental skills provided in Additional file: Figure S3 . Table 2 Developmental Skill Loss . Skill Loss All Cases Age Loss (yr) Time Gain to Loss (yr) Total N % Loss (95% CI, N) Mean (SEM, N) Median (5%, 95%) Mean (SEM, N) Median (5%, 95%) Gross Motor Lift Head 624 6.6 (4.8–8.8, 41)* 3.9 (1.2, 18) 1.6 (0.5, 14.0) 3.4 (1.4, 15) 1.2 (0.2, 13.9) Roll From Tummy 1175 34.0 (31.4–36.8, 400) 3.6 (0.3, 281) 2.0 (0.7, 12.0) 2.9 (0.3, 255) 1.4 (0.1, 10.7) Sit With Support 628 13.2 (10.7–16.0, 83) 5.2 (0.6, 61) 3.0 (1.0, 12.5) 4.6 (0.7, 53) 2.4 (0.2, 11.9) Sit Without Support 1191 19.4 (17.2–21.7, 231) 5.1 (0.4, 179) 3.0 (0.9, 13.0) 4.4 (0.4, 170) 2.3 (0.2, 12.7) Come To Sit 1018 26.8 (24.2–29.6, 273) 4.8 (0.3, 201) 3.0 (1.0, 13.0) 3.6 (0.3, 181) 1.7 (0.2, 12.2) Crawl 868 25.3 (22.5–28.3, 220) 3.8 (0.3, 149) 2.0 (1.2, 12.0) 2.8 (0.3, 140) 1.2 (0.2, 11.1) Stand With Support 542 28.4 (24.7–32.3, 154) 5.3 (0.6, 96) 2.2 (1.0, 17.5) 4.3 (0.7, 80) 1.2 (0.2, 18.2) Pull To Stand 831 42.1 (38.8–45.5, 350) 4.1 (0.3, 266) 2.5 (1.3, 12.0) 2.9 (0.3, 253) 1.0 (0.1, 11.0) Walk With Support 969 25.9 (23.2–28.7, 251) 4.8 (0.3, 188) 3.0 (1.2, 13.5) 3.5 (0.4, 172) 1.3 (0.1, 12.2) Stand Independently 411 29.0 (24.7–33.5, 119) 7.8 (0.8, 74) 6.5 (1.0, 22.4) 6.6 (0.9, 58) 5.3 (0.1, 22.0) Walk Independently 727 28.3 (25.1–31.7, 206) 7.8 (0.5, 177) 6.0 (1.3, 22.0) 6.0 (0.5, 164) 4.0 (0.0, 20.0) Ran 10 Feet 188 42.6 (35.6–49.7, 80) 6.1 (0.8, 48) 4.0 (1.0, 16.0) 5.0 (1.1, 32) 2.3 (0.3, 14.8) Up Stairs With Help 343 30.3 (25.6–35.3, 104) 7.3 (0.8, 55) 6.5 (1.4, 15.0) 4.4 (0.8, 43) 3.0 (0.3, 12.0) Up Stairs Without Help 318 41.5 (36.2–47.0, 132) 4.7 (0.4, 96) 3.0 (1.4, 15.0) 2.8 (0.4, 81) 1.4 (0.2, 10.6) Down Stairs With Help 280 31.1 (25.8–36.6, 87) 8.2 (0.9, 49) 7.3 (1.5, 22.0) 6.4 (1, 35) 5.0 (0.2, 17.0) Down Stairs WO Help 241 44.0 (37.8–50.3, 106) 4.8 (0.5, 77) 3.0 (1.3, 14.0) 3.1 (0.5, 65) 1.0 (0.1, 12.5) Fine Motor Hold Bottle 1090 60.5 (57.5–63.3, 659) 2.5 (0.1, 557) 2.0 (1.0, 6.0) 1.8 (0.1, 497) 1.2 (0.2, 5.0) Reach For Toy 1197 56.8 (54.0-59.6, 680) 2.2 (0.1, 569) 1.7 (1.0, 4.5) 1.6 (0.1, 488) 1.2 (0.4, 3.7) Raking Grasp 571 58.0 (53.9–62.0, 331) 2.8 (0.2, 219) 2.0 (1.0, 7.0) 2.2 (0.3, 148) 1.3 (0.3, 8.0) Transfer Objects 942 71.0 (68.1–73.9, 669) 2.2 (0.1, 526) 1.8 (1.0, 4.5) 1.4 (0.1, 428) 1.0 (0.3, 3.5) Pincer Grasp 941 76.2 (73.4–78.8, 717) 2.3 (0.1, 602) 2.0 (1.0, 5.0) 1.3 (0.1, 511) 1.0 (0.2, 3.4) Finger Feeding 1130 63.7 (60.9–66.5, 720) 2.5 (0.1, 624) 2.0 (1.0, 5.8) 1.6 (0.1, 540) 1.0 (0.2, 4.2) Turn Pages in Book 356 74.7 (70.0–79.0, 266) 2.4 (0.1, 156) 2.0 (1.2, 4.0) 1.3 (0.1, 113) 1.0 (0.3, 3.0) Expressive Social Smile 1219 18.2 (16.1–20.4, 222) 2.2 (0.2, 200) 1.5 (0.8, 4.0) 1.6 (0.1, 178) 1.2 (0.3, 3.2) Cooing 1153 40.2 (37.4–43.1, 464) 1.6 (0.1, 324) 1.3 (0.5, 3.0) 1.2 (0.1, 288) 1.0 (0.2, 2.6) Babbling 1167 55.4 (52.6–58.3, 647) 1.9 (0.1, 518) 1.5 (0.8, 4.0) 1.1 (0.1, 459) 0.8 (0.2, 2.7) Words With Meaning 940 88.6 (86.5–90.5, 833) 2.0 (0.1, 755) 1.5 (0.9, 4.0) 1.0 (0.1, 652) 0.5 (0.1, 2.5) Spoken Phrases 287 87.8 (83.7–91.2, 252) 2.5 (0.1, 202) 2.0 (1.2, 5.0) 1.0 (0.1, 144) 0.5 (0.1, 2.5) Wave Bye 716 87.8 (85.3–90.1, 629) 2.0 (0.1, 497) 1.5 (0.8, 4.0) 1.0 (0.1, 422) 0.7 (0.1, 2.5) Point for Wants 373 67.3 (62.4–71.9, 251) 2.3 (0.2, 184) 1.9 (1.0, 4.0) 1.2 (0.2, 152) 0.7 (0.2, 3.0) Shared Stories 15 66.7 (38.4–88.2, 10)* 2.7 (0.2, 6) 2.5 (2.0, 3.0) 1.1 (0.1, 3) 1.0 (1.0, 1.2) Receptive Quiet To Voice 1101 23.7 (21.3–26.3, 261) 1.8 (0.1, 218) 1.5 (1.0, 3.5) 1.4 (0.1, 171) 1.2 (0.4, 2.9) Respond To Sounds 621 15.8 (13.1–18.8, 98) 1.6 (0.1, 78) 1.5 (0.5, 3.0) 1.4 (0.1, 37) 1.2 (0.5, 2.9) Play Peek-A-Boo 396 57.8 (52.9–62.6, 229) 1.9 (0.1, 111) 1.5 (0.8, 3.0) 1.1 (0.1, 87) 0.9 (0.2, 2.5) Respond To Words 583 19.6 (16.5–22.9, 114) 1.9 (0.1, 73) 1.5 (1.0, 3.0) 1.1 (0.1, 55) 0.8 (0.3, 2.5) Respond To Own Name 613 17.6 (14.7–20.8, 108) 1.7 (0.1, 75) 1.5 (0.8, 3.0) 0.9 (0.1, 52) 0.8 (0.2, 2.2) Inhibit To No 887 26.0 (23.2–29.0, 231) 2.0 (0.1, 161) 1.6 (1.0, 4.0) 0.9 (0.1, 121) 0.7 (0.2, 2.1) Commands With Gesture 727 48.1 (44.5–51.8, 350) 2.2 (0.1, 230) 1.9 (1.0, 5.0) 1.1 (0.1, 172) 0.8 (0.2, 3.0) Commands WO Gesture 594 45.8 (41.8–49.8, 272) 2.4 (0.1, 171) 2.0 (1.1, 5.0) 1.2 (0.1, 128) 0.7 (0.2, 3.1) Identify Body Parts 265 46.8 (40.8–52.8, 124) 2.5 (0.2, 68) 2.0 (1.1, 5.0) 1.1 (0.2, 55) 0.7 (0.2, 2.0) Point to 1 Color 298 20.5 (16.2–25.3, 61) 2.2 (0.2, 28) 2.0 (0.3, 4.0) 0.7 (0.1, 21) 0.6 (0.2, 1.5) Social /Adaptive Like Being Held 1174 19.5 (17.3–21.8, 229) 1.8 (0.1, 196) 1.5 (0.6, 3.5) 1.6 (0.1, 160) 1.4 (0.4, 2.9) Attention to Loud Sounds 567 19.2 (16.1–22.6, 109) 1.8 (0.1, 80) 1.5 (1.0, 3.0) 1.1 (0.1, 29) 1.0 (0.2, 2.3) Eyes Fix and Follow 1161 29.7 (27.1–32.4, 345) 1.7 (0.1, 278) 1.5 (0.8, 3.0) 1.3 (0, 214) 1.1 (0.4, 2.4) Play Pat-A-Cake 178 78.7 (72.2–84.2, 140) 1.9 (0.1, 71) 1.5 (1.0, 3.0) 1.0 (0.1, 53) 0.7 (0.2, 2.2) Desire Social Attention 536 17.9 (14.8–21.3, 96) 2.0 (0.2, 67) 1.5 (0.8, 4.0) 1.3 (0.2, 37) 1.1 (0.4, 2.0) Imitate Peers 134 73.1 (65.2–80.2, 98) 2.4 (0.3, 66) 1.9 (0.9, 6.0) 1.5 (0.4, 35) 0.7 (0.2, 4.5) Been Independent 224 42.0 (35.6–48.5, 94) 2.9 (0.4, 49) 2.0 (1.0, 7.0) 2.0 (0.6, 32) 0.8 (0.2, 4.0) Drinks WO Help 391 62.4 (57.5–67.1, 244) 3.0 (0.3, 153) 2.0 (1.2, 6.4) 2.0 (0.3, 108) 1.0 (0.2, 6.3) Uses Utensils With Help 429 52.9 (48.2–57.6, 227) 3.0 (0.2, 131) 2.0 (1.3, 7.0) 1.6 (0.2, 103) 1.0 (0.2, 5.0) Uses Utensils WO Help 169 73.4 (66.4–79.7, 124) 3.0 (0.3, 71) 2.5 (1.3, 5.0) 1.2 (0.2, 50) 0.7 (0.2, 3.0) Table 2 Legend : The total number (N) of participants with information available on skill loss is shown in the first column. Column two displays the percentage (%), 95% Confidence Interval (CI) and number of individuals (N) who lost a previously gained skill for each skill for all cases. * Indicates where the Clopper-Pearson exact method was used to calculate the CI. The mean age of skill loss in years (yr), with the standard error of the mean (SEM) and the median age of skill loss with 5–95% intervals are presented for cases with known age of loss. Similarly, for the time from gain to loss the mean, SEM, median and 5–95% intervals are shown for cases with known age of gain and loss. Regain of developmental skills While developmental delay and regression are well known features of RTT, it has been recognized that there are instances of regain of previously lost developmental skills in RTT, primarily in the Gross Motor domain [ 47 – 50 ]. For the developmental skills captured, we characterized the percentage of participants who regained each skill and age regained (Table 3 ). The range of percentage of regain of individual skills ranged from 2.1% (Play Pat-A-Cake) to 80.6% (Social Smile). For the majority of skills (31 of 51, 60.8%), the percentage of participants who lost and regained that skill was under 20%. In general, low level social and receptive language skills (such as Social Smile, Desire Social Attention, Respond to Own Name) were skills with the highest percentage of regain amongst participants, whereas a low percentage of participants regained higher level skills. The mean age of regaining skills ranged from 2.7 years old (Respond to Sounds) to 8.0 years old (Up Stairs With Help), and the median ranged from 2.0 years old (Respond to Sounds, Attention to Loud Sounds) to 9.0 years old (Up Stairs With Help). Of the 51 developmental skills regained, 46 (90.2%) had a median age of regain under 6 years of age. The percentage of individuals who lost a specific skill and then regained that skill after 6 years of age was under 10% (out of all who lost the skill) for all 51 skills, and 5% or less for 40 of the 51 skills (78.4%). Cumulative incidence curves (Kaplan-Meyer 1-Survival curves) of regain of representative developmental skills are shown in Fig. 3 , with regain curves for all developmental skills provided in Additional file 8: Figure S4 . Broadly, while there is evidence of skill regain after loss in RTT, the frequency is generally low and typically occurs before 6 years of age. Table 3 Developmental Skill Regain . Skill Regain Regain (All Cases) Age Regain (yr) Time Loss to Regain (yr) Total N % Regain (95% CI, N) Mean (SEM, N) Median (5%, 95%) % Regain > 6 yo (N) Mean (SEM, N) Median (5%, 95%) % Regain > 2yrs post loss (N) Gross Motor Lift Head 41 36.6 (23-51.8, 15) 3.6 (0.7, 5) 3.0 (2.0, 6.0) 0.0 (0) 1.8 (0.6, 5) 1.4 (0.5, 4.0) 15.6 (2) Roll From Tummy 400 14.0 (10.8–17.6, 56) 3.3 (0.4, 35) 2.7 (0.9, 7.3) 1.3 (4) 1.4 (0.3, 32) 0.8 (0.0, 3.5) 3.0 (7) Sit With Support 83 31.3 (22.0-41.8, 26) 3.4 (0.6, 14) 3.0 (1.0, 7.0) 3.0 (2) 1.5 (0.4, 12) 1.0 (0.2, 3.3) 6.4 (3) Sit Without Support 231 25.1 (19.8–31.0, 58) 5.1 (0.5, 43) 4.0 (1.6, 11.8) 7.0 (13) 2.3 (0.4, 41) 2.0 (0.2, 6.0) 10.7 (16) Come To Sit 273 14.3 (10.5–18.8, 39) 4.9 (0.7, 29) 3.5 (1.3, 12.0) 3.9 (9) 2.0 (0.5, 28) 1.0 (0.0, 7.0) 5.4 (9) Crawl 220 5.5 (2.8–9.3, 12)* 4.8 (1.1, 10) 2.5 (1.8, 12.0) 1.8 (3) 1.9 (0.6, 10) 1.1 (0.3, 6.0) 2.4 (3) Stand With Support 154 11.7 (7.3–17.4, 18) 6.1 (1.4, 12) 4.0 (1.7, 13.0) 5.0 (6) 2.3 (0.8, 11) 1.0 (0.1, 5.7) 5.5 (4) Pull To Stand 350 11.1 (8.1–14.7, 39) 4.2 (0.7, 23) 2.5 (1.6, 12.4) 1.5 (4) 1.3 (0.4, 22) 0.7 (0.1, 3.3) 1.4 (3) Walk With Support 251 16.7 (12.5–21.7, 42) 5.5 (0.7, 32) 4.0 (1.8, 13.0) 5.2 (10) 2.0 (0.6, 31) 1.0 (0.1, 6.0) 4.4 (5) Stand Independently 119 12.6 (7.5–19.3, 15) 4.9 (1.4, 8) 2.8 (1.7, 12.4) 3.1 (3) 0.9 (0.4, 8) 0.5 (0.1, 3.7) 1.7 (1) Walk Independently 206 20.4 (15.3–26.2, 42) 5.5 (0.7, 30) 4.3 (1.3, 13.0) 6.8 (11) 0.9 (0.2, 28) 0.7 (0.0, 2.0) 0.7 (1) Ran 10 Feet 80 8.8 (3.6–17.2, 7)* 4.8 (1.4, 7) 4.0 (1.7, 12.4) 1.5 (1) 0.9 (0.3, 7) 0.8 (0.1, 2.2) 2.1 (1) Up Stairs With Help 104 13.5 (7.8–20.9, 14) 8.0 (1.2, 9) 9.0 (3.0, 12.4) 7.3 (6) 3.9 (1.2, 9) 3.2 (0.1, 10.6) 15.9 (5) Up Stairs Without Help 132 9.8 (5.3–16.3, 13)* 5.8 (1.1, 9) 5.5 (2.0, 12.0) 3.8 (4) 2.7 (1.4, 7) 0.5 (0.4, 10.6) 3.2 (2) Down Stairs With Help 87 11.5 (5.9–19.3, 10) 7.8 (1.5, 6) 6.6 (3.0, 12.4) 5.6 (4) 3.6 (1.4, 5) 4.1 (0.1, 8.0) 10.3 (3) Down Stairs WO Help 106 8.5 (4.0-15.5, 9)* 6.6 (0.8, 3) 6.6 (5.3, 8.0) 2.2 (2) 2.8 (0.7, 3) 2.3 (2.0, 4.1) 2.9 (2) Fine Motor Hold Bottle 659 9.6 (7.4–12.1, 63)* 3.8 (0.4, 48) 3.1 (1.3, 10.0) 1.2 (5) 1.7 (0.3, 44) 1.0 (0.2, 4.8) 2.5 (11) Reach For Toy 680 20.6 (17.7–23.7, 140) 3.4 (0.2, 97) 3.0 (1.5, 6.9) 1.5 (7) 1.7 (0.2, 96) 1.1 (0.2, 4.0) 4.8 (22) Raking Grasp 331 9.4 (6.5–13.0, 31)* 3.2 (0.4, 19) 3.0 (1.3, 6.0) 0.4 (1) 1.5 (0.3, 18) 1.0 (0.2, 4.0) 1.6 (3) Transfer Objects 669 5.5 (3.9–7.5, 37)* 4.1 (0.5, 28) 3.0 (1.5, 9.0) 0.9 (4) 1.8 (0.3, 27) 1.0 (0.0, 4.5) 1.8 (8) Pincer Grasp 717 9.9 (7.8–12.3, 71)* 5.0 (0.4, 48) 4.0 (1.7, 12.0) 2.5 (12) 2.2 (0.3, 43) 1.5 (0.3, 6.0) 3.0 (14) Finger Feeding 720 10.4 (8.3–12.8, 75) 4.0 (0.3, 53) 3.5 (1.7, 7.0) 1.1 (5) 1.6 (0.3, 51) 1.0 (0.2, 4.5) 2.2 (10) Turn Pages in Book 266 5.3 (2.9–8.7, 14)* 4.3 (0.8, 6) 4.5 (2.0, 7.0) 0.4 (1) 1.9 (0.8, 5) 1.0 (0.4, 4.5) 1.5 (2) Expressive Social Smile 222 80.6 (75.1–85.5, 179) 3.0 (0.2, 137) 2.5 (1.1, 6.0) 3.6 (4) 1.3 (0.2, 133) 0.9 (0.2, 3.5) 13.4 (19) Cooing 464 21.6 (18-25.4, 100) 3.0 (0.3, 73) 2.5 (1.2, 6.0) 1.2 (2) 1.5 (0.3, 73) 1.0 (0.2, 3.3) 4.8 (11) Babbling 647 28.6 (25.2–32.2, 185) 3.0 (0.2, 154) 2.5 (1.3, 6.5) 2.0 (9) 1.4 (0.2, 150) 0.9 (0.2, 4.0) 6.7 (28) Words With Meaning 833 16.6 (14.1–19.2, 138) 3.5 (0.2, 119) 3.0 (1.5, 7.0) 1.7 (9) 1.6 (0.2, 114) 1.0 (0.2, 4.3) 3.5 (22) Spoken Phrases 252 9.9 (6.5–14.3, 25)* 5.3 (0.7, 19) 4.3 (2.0, 9.0) 2.5 (5) 2.8 (0.7, 19) 1.5 (0.0, 6.0) 4.9 (8) Wave Bye 629 7.0 (5.1–9.3, 44)* 3.2 (0.3, 30) 3.0 (1.5, 7.0) 0.6 (3) 1.7 (0.3, 26) 1.1 (0.2, 5.0) 1.0 (4) Point for Wants 251 14.3 (10.4–19, 36) 4.6 (0.5, 27) 4.0 (2.0, 9.0) 2.1 (4) 2.7 (0.5, 26) 2.0 (0.5, 7.7) 7.3 (11) Shared Stories 10 10.0 (0.3–44.5, 1)* - (-, 0) - 0.0 (0) - (-, 0) - 0.0 (0) Receptive Quiet To Voice 261 66.7 (60.8–72.2, 174) 3.1 (0.2, 128) 2.7 (1.4, 6.0) 3.9 (6) 1.4 (0.1, 127) 1.0 (0.2, 3.0) 14.5 (24) Respond To Sounds 98 79.6 (70.9–86.7, 78) 2.7 (0.2, 52) 2.0 (1.2, 5.0) 1.5 (1) 1.3 (0.2, 50) 1.0 (0.2, 3.5) 15.1 (9) Play Peek-A-Boo 229 7.4 (4.4–11.6, 17)* 4.1 (0.6, 9) 4.5 (2.0, 8.0) 0.5 (1) 1.8 (0.5, 8) 1.5 (0.3, 3.5) 3.0 (3) Respond To Words 114 52.6 (43.5–61.7, 60) 3.9 (0.6, 36) 3.0 (1.5, 8.0) 7.9 (5) 1.6 (0.3, 30) 1.0 (0.2, 5.0) 14.9 (8) Respond To Own Name 108 72.2 (63.3–80.1, 78) 3.5 (0.4, 52) 2.8 (1.3, 6.8) 6.7 (4) 1.7 (0.4, 45) 1.0 (0.2, 4.5) 20.4 (11) Inhibit To No 231 45.5 (39.1–51.9, 105) 3.9 (0.3, 62) 3.3 (1.5, 8.0) 4.5 (7) 2.0 (0.3, 58) 1.5 (0.3, 5.5) 12.0 (14) Commands W Gesture 350 30.6 (25.9–35.5, 107) 4.1 (0.4, 55) 3.0 (1.6, 9.0) 3.5 (7) 1.9 (0.3, 54) 1.2 (0.2, 5.7) 5.6 (9) Commands WO Gesture 272 31.6 (26.3–37.3, 86) 3.9 (0.3, 44) 3.3 (1.7, 7.0) 2.2 (4) 2.0 (0.3, 43) 1.5 (0.3, 5.7) 10.3 (13) Identify Body Parts 124 14.5 (9.1–21.4, 18) 4.5 (0.7, 9) 3.5 (1.8, 8.0) 2.0 (2) 2.2 (0.5, 8) 2.0 (0.1, 4.0) 7.1 (4) Point to 1 Color 61 32.8 (21.9–45.1, 20) 5.9 (1.3, 10) 5.0 (1.8, 15.0) 7.4 (3) 3.3 (1.1, 6) 1.7 (0.1, 7.5) 17.4 (2) Social/Adaptive Like Being Held 229 73.4 (67.4–78.8, 168) 3.4 (0.2, 139) 3.0 (1.2, 7.0) 5.6 (9) 1.8 (0.2, 136) 1.1 (0.2, 4.2) 24.4 (41) Attention to Sounds 109 68.8 (59.7–77, 75) 2.8 (0.2, 50) 2.0 (1.0, 6.5) 3.9 (3) 1.4 (0.2, 47) 1.0 (0.2, 4.0) 13.8 (9) Eyes Fix and Follow 345 73.6 (68.8–78.1, 254) 3.3 (0.2, 191) 2.6 (1.4, 7.0) 7.4 (15) 1.5 (0.1, 182) 1.0 (0.2, 4.7) 16.0 (34) Play Pat-A-Cake 140 2.1 (0.4–6.1, 3)* 6.5 (1.5, 2) 5.0 (5.0, 8.0) 0.8 (1) 3.5 (1.5, 2) 2.0 (2.0, 5.0) 1.7 (1) Desire Social Attention 96 72.9 (63.5–81.1, 70) 3.0 (0.3, 44) 2.5 (1.2, 6.0) 3.8 (2) 1.3 (0.2, 41) 1.0 (0.1, 4.0) 11.3 (6) Imitate Peers 98 11.2 (6.0-18.5, 11) 4.0 (0.5, 9) 4.0 (2.2, 6.6) 1.2 (1) 2.3 (0.4, 9) 2.0 (0.8, 4.3) 7.3 (4) Been Independent 94 17.0 (10.4–25.5, 16) 5.7 (1.6, 11) 4.0 (2.0, 8.0) 6.5 (3) 2.3 (0.7, 8) 1.2 (0.3, 6.0) 8.1 (3) Drinks WO Help 244 8.6 (5.4–12.9, 21)* 5.3 (1.1, 9) 4.5 (1.8, 12.0) 1.2 (2) 2.8 (1, 9) 1.5 (0.4, 8.5) 3.1 (3) Uses Utensils W Help 227 12.8 (8.9–17.5, 29) 5.5 (0.7, 16) 4.5 (1.8, 9.0) 3.1 (5) 2.3 (0.6, 11) 1.5 (0.3, 4.5) 4.9 (5) Uses Utensils WO Help 124 8.9 (4.5–15.3, 11)* 6.7 (1.5, 5) 8.0 (2.0, 10.0) 3.2 (3) 4.1 (1.3, 5) 5.5 (0.5, 7.0) 6.1 (3) Table 3 Legend : The total number (N) of participants with information available on skill regain is shown in the first column. Column two displays the total percentage (%), 95% Confidence Interval (CI) and number of individuals (N) who regained a previously lost skill for each skill for all cases. * Indicates where the Clopper-Pearson exact method was used to calculate the CI. The mean age of skill regain in years (yr), with the standard error of the mean (SEM) and the median age of skill regain with 5–95% intervals is presented for cases with identified age of regain. The percentage of individuals (and number) who regained a skill after 6 years old (yo) is shown. Similarly, the mean, SEM, median, and 5–95% intervals for time from loss to regain in years (yr) is shown as well as the percentage of individuals (and number) who regained a skill more than 2 years after losing that skill is displayed for cases in which the age of loss and regain is known. To account for variation in the age of loss for specific skills (Table 2 ), we calculated the time from loss to regain for each developmental skill (Table 3 ). The mean time from loss to regain ranged from 0.9 years (Stand Independently, Walk Independently, Ran 10 Feet) to 4.1 years (Uses Utensils Without Help), and the median time from loss to regain ranged from 0.5 years (Stand Independently, Up Stairs Without Help) to 5.5 years (Uses Utensils Without Help). Nearly all skills had a median time from loss to regain of 2 years or less (46 of 51, 90.2%). For 35 of the 51 developmental skills (68.6%), the percentage of participants who regained that skill (out of all who lost that skill) beyond 2 years from loss was less than 10%, and for 25 of the 51 skills this percentage was less than 5%. Notably, skills with a low percentage of regain beyond 2 years from loss include all the fine motor hand skills (Ranging from 1.5% for Turning Pages in Book to 4.8% for Reach For Toy), more advanced expressive verbal skills such as Words with Meaning (3.5%) or Spoken Phrases (4.9%), and higher-level gross motor skills such as Stand Independently (1.7%) or Walk Independently (0.7%), with the exception of Up Stairs With Help or Down Stairs With Help. In contrast, lower-level skills and non-verbal Receptive skills had a higher percentage of regain beyond 2 years from loss. Cumulative incidence curves (Kaplan-Meyer 1-Survival curves) of the time from loss to regain for representative developmental skills are shown in Fig. 3 , with loss to regain curves for all developmental skills provided in Additional file 9: Figure S5 . Overall, when skills are regained after loss, for the majority of skills this regain occurs within the first 2 years after loss. Incidence developmental skill gain or regain in one-year intervals Because we observed that developmental skill gain, loss, or regain in RTT primarily occurs within the first couple years of life for the majority of skills (Tables 1 – 3 ), we were interested in evaluating the incidence of either gaining or regaining a developmental skill in one-year intervals spanning from 0–20 years old. Figure 4 displays the percentage of eligible participants in each one-year interval who gained or regained a specific developmental skill from age 1–10 years old. We found that the frequency of gain or regain for any of the skills drops to < 2% per year after age 10 ( Additional file 9: Figure S6 for results spanning the entire age range). For all skills, the one-year incidence of gain or regain is below 4% after 4 years of age. After age 6, the one-year incidence of gain or regain is less than 1% per year for all skills except for Responds To Familiar Words, Responds to Own Name, Point to 1 Color, or Eyes Fix and Follow. We calculated the frequency of gaining or regaining one or more of any of the 51 skills during one-year intervals (Fig. 4 ). There is a sharp drop-off in frequency with increasing age, with the overall percentage of eligible participants who gain or regain at least 1 of any of the 51 skills dropping below 6.3% per year after 6 years of life. While this demonstrates that after a given age of life the likelihood of gaining or regaining even one skill becomes unlikely, we were interested if selecting a more limited set of developmental skills would further decrease this likelihood. To evaluate this, we performed a similar analysis on a restricted set of developmental skills, removing early acquired skills for which attainment (either gain or regain) might have limited functional meaningfulness or may have been difficult to clearly assess ( e.g . Lift Head, Quiet to Voice, Respond to Sounds, Social Smile, Like Being Held) or skills with a high rate of gain or regain beyond 3–4 years old ( e.g. Point to 1 Color). The thirteen skills removed from this restricted analysis are indicated by grey highlights in Fig. 4 , leaving the remaining 38 skills for analysis. In this restricted set of developmental skills, the percentage of participants who gained at least one of these 38 skills fell below 5% per year after 6 years of life. This demonstrates that further restriction of which developmental skills to include in an analysis of the one-year incidence of gain or regain of one or more skills, based on consideration of meaningfulness and impact of acquiring a skill on the affected individual, could further decrease the one-year frequency of gain or regain of any of the selected skills. Discussion Alteration of the developmental trajectory of psychomotor skills ("developmental milestones") is a major feature of RTT [ 5 ], typically described as “apparently normal” development in early infancy, followed by developmental delay, subsequent regression of previously acquired skills, and then stabilization with some regain of previously lost skills. Previous studies [ 12 – 14 , 51 , 52 ] primarily presented the proportion of individuals with RTT that gain or lose a skill with limited quantitative information on the timing of skill gain or loss or the proportion and timing of regaining previously lost skills. These gaps reflect the challenge of gathering sufficient data in rare disorders such as RTT. To address these gaps, we analyzed data on developmental skill trajectory in a large cohort (n = 1228) of females with Classic RTT collected over the sixteen years from the US RNHS. Our goal was to expand understanding of developmental skill trajectory with granular information on the proportion and timing of skill gain, loss, and regain on a larger set of developmental skills than previously characterized [ 13 ] to inform trial design and provide a natural history arm in novel disease modifying therapies for RTT. These data are the most exhaustive description of developmental skill trajectory in RTT and are consistent with published findings [ 12 , 13 ]. Broadly, we observed a greater percentage of individuals gaining rudimentary skills (acquired earlier in life) than more complex, later-acquired skills. For nearly all the skills assessed (50 of 51), the median age of acquisition (when gained) was under 2 years old, and for over half of the skills (26 of 51), 95% of individuals who gained a specific skill did so by 2 years old. Consistent with this early age of acquisition of skills, < 5% of individuals gained any skill after age 4 and < 2.5% after 6 years, indicating that gaining a new skill beyond these ages is highly unlikely. While the age of diagnosis of RTT has decreased since the first description of the disorder in English [ 5 , 12 , 46 , 53 ], the current median age of diagnosis (2.7 years) [ 46 ] is more than one year after both the previously reported median age of regression (18 months, 1.5 years) [ 12 ] and the median age of skill loss reported herein (Table 2 ). Comparing the age of skill acquisition to the expected age (based on CDC developmental milestone surveillance guidelines) [ 44 ] more than half of individuals with RTT did not acquire a specific skill by the CDC guideline threshold age. For nearly all CDC skills (39 of 41), > 20% of affected individuals did not obtain a specified skill. Importantly, a significant percentage of individuals with RTT do not obtain major developmental milestones by the age recommended by the CDC guidelines that should occur before the onset of regression (e.g. Pull to Stand, Walk Independently, Pincer Grasp, Words With Meaning). Furthermore, a significant percentage of people with RTT do not acquire many early developmental skills expected to be achieved before 6 months old (e.g. Lift Head, Hold Bottle). These observations have at least two relevant implications. First, if the current CDC surveillance guidelines were universally followed, it is likely that a larger number of individuals with RTT would be identified earlier. Second, it questions the concept that early skill development is “apparently normal” in RTT [ 54 , 55 ], which has been questioned for nearly four decades (see comprehensive review [ 15 ]). Families often report that they had suspicion about their child’s development even within the first six months of life [ 12 , 15 , 56 ], and systematic retrospective analysis of early home videos of children subsequently diagnosed with RTT identified characteristic developmental abnormalities [ 15 , 57 – 59 ]. Hence, earlier genetic testing upon first noticing lack of skill gains could facilitate earlier diagnosis. Development of potentially disease modifying therapies, such as gene therapy, could result in better outcomes with earlier identification. Ultimately, one might argue that newborn screening for pathogenic MECP2 variants could provide rapid, early diagnosis of RTT enabling early interventions; however, this could carry significant risk as the mere presence of pathogenic MECP2 variants is not sufficient to establish the clinical emergence of RTT [ 6 , 60 ]. Together, early detection of alterations in early developmental milestones, paired with genetic testing, can lead to specific prediction of which individuals would benefit from early treatment with disease modifying therapies. A general pattern emerged in our analysis of skill loss. More advanced and later acquired skills are lost in a larger percentage of individuals compared to loss of early developmental skills. For example, the frequency of loss of fine motor skills and expressive communication skills (especially verbal) was high, consistent with the fact that loss of hand skills and verbal communication are defining features of RTT and necessary criteria for the clinical diagnosis of RTT [ 6 ]. Most of the documented skill loss occurs within 2 years of initial gain. However, gross motor skill loss generally occurred over longer time intervals and at older ages than other skill domains (Fig. 2 ). This aligns with the concept of “Late Motor Decline” [ 7 ], evaluations focused on longitudinal gross motor performance [ 61 , 62 ], and recognition of increasing rigidity and Parkinsonian features with age [ 10 , 11 ]. The recognition that regression of most domains (aside from Gross Motor) typically occurs early in life and within the first 2 years after gain is important for counseling and discussion with caregivers. Similarly, acknowledging that loss of previously acquired gross motor skills may occur over a protracted time period and influenced by progressive motor tone abnormalities and Parkinsonian features underscores recommendations for medical interventions that modify tone and long-term physical therapies to maintain gross motor function. The period after regression (Stage III, the “Pseudostationary” stage [ 7 , 63 ]) historically has been characterized by the lack of further skill loss, although this has been noted to be invalid [ 7 ], and here we demonstrate that slow regression can occur in this stage. Additionally, reports of some degree of regaining lost skills during Stage III exist. While we observed that this can occur, it is rare (< 20% of individuals), predominantly in lower-level skills, and infrequent for higher-level skills. Further, regain of skills primarily occurs before age 6 years and within 2 years of loss. Thus, while regaining previously lost skills can occur in RTT, it is uncommon, occurs early in life, shortly after loss, and more frequently for lower-level skills. Analysis of the one-year incidence of skill gain or regain demonstrated that individual skill gain or regain occurs early in life and drops off for nearly all skills by age 6 years. Furthermore, the one-year incidence of gaining or regaining at least one of the 51 skills assessed dropped below 10% after age 6 years. Overall, these results indicate that the trajectory of developmental skill gain, loss, and regain in RTT occurs early in life. After age 6 years it is unlikely that a skill not previously obtained will be gained or that a skill previously lost will be regained. These results have implications for assessing therapeutic interventions, especially potentially disease-modifying interventions. The ability to describe those skills unlikely to be gained or regained as part of the natural history of RTT could be crucial in establishing reasonable trial outcomes to demonstrate improvement. This is especially critical for clinical trials that preclude conducting studies in a double-blind fashion. Such trials involving gene therapy require invasive procedures in children, utilize vector-based therapies with mortality and morbidity risks, require additional medications such as immunosuppressive agents that carry unacceptable risks in a placebo treated population, and could result in clinical features carrying the risk of unintentional unblinding. The advantages of these developmental endpoints are: 1) they are easily defined, 2) binary, and 3) likely to be emergent with an effective treatment paradigm. Current clinical trial outcome measures such as the Clinical Global Impression of Improvement (CGI-I) [ 39 ] or the Rett Syndrome Behavioral Questionnaire (RSBQ) [ 64 – 66 ] have limitations in terms of rater consistency (CGI-I) and limited coverage of important clinical features and sensitivity to change (RSBQ). The ability to apply these real-world natural history data to clinical trials offers a step forward. Importantly, a critical component that recognizes FDA guidance is the consideration of the “meaningfulness” of the gain or regain of a specific skill [ 67 – 73 ]. The impact of acquiring a skill on the overall quality of life for an affected individual, and their family, is likely not equivalent across the skills evaluated in this study. Gaining/regaining skills that impact adaptive activities, such as walking independently, self-feeding and self-care, and effectively communicating are likely to be more impactful than gaining/regaining lower-level skills such as lifting head or sitting with support. Thus, it is important to determine which skills would be most meaningful through input from those affected and their caregivers. As people with RTT have markedly impaired communication, input from caregivers on meaningfulness of specific skills is critical [ 67 – 73 ]. As demonstrated, limiting the set of developmental skills considered impacts the one-year incidence of either gaining or regaining any of the selected skills. The incorporation of caregiver input to define the most impactful skills, in combination with the expected trajectory of skill gain, loss, and regain, has robust potential to guide clinical trial design and implementation. Furthermore, the rich data provided from this study could be utilized to conduct “emulation” trials to define the expected trajectory and likelihood of gain or regain in an untreated cohort as a comparator to participants in an open label trial. Although this work presents detailed information gathered from a large cohort of people with RTT, limitations are recognized. First, participants were primarily white, non-Hispanic participants in the US with sufficient resources to participate in this study [ 35 ]. While efforts were made to maximize participation and representation, the costs, associated loss of income, and difficulties of travel to examination sites could have significantly impacted the composition of the participants. This limits the extrapolation of these findings to other populations, including those outside of the US and from underrepresented populations. Second, the data collected on skill gain, loss, and regain was retrospectively collected from caregivers with the associated potential of recall bias. To mitigate this limitation, every effort was made to encourage families to refer to pictures, videos, baby books, medical records, or association with specific dates such as birthdays or holidays. Further, skill gain, loss, or regain was reviewed at every visit and considered in relation to the current ability of the participant. Because the occurrence of a skill event (gain, loss, or regain) is more likely to be remembered than the specific age of occurrence, we made no attempt to impute missing data for age of event when caregiver recall was not possible. Future studies could employ systematic evaluation of retrospectively captured video data from affected individuals [ 74 ] or prospectively captured longitudinal birth cohort studies [ 75 ], although the rare occurrence of RTT makes the latter challenging. Despite these limitations, the results presented here based on data collected from more than 1200 individuals with RTT through repeated, in-person assessments represents the largest body of work in this disorder and provides confidence in the reliability and representativeness of these findings. Future studies evaluating genotype/phenotype relationships and development of probabilistic models for the likelihood of individual or multiple skill gain/loss/regain will further expand our understanding of RTT. Conclusions In summary, this comprehensive analysis demonstrates that the percentage of individuals with RTT who gain specific skills depends heavily on the developmental level of the skill, with higher-level abilities being acquired by fewer individuals. Skill gain, loss, and regain generally occur early in life, with a developmentally stable period expected after 4–6 years of age, except for gross motor skills which show a wider age range for skill loss. These natural history data provide fundamental information that can improve our understanding of developmental trajectories in RTT, facilitate earlier diagnosis, inform medical and therapeutic interventions, and guide clinical trial design in RTT. Abbreviations CDC: Centers for Disease Control CGI-I: Clinical Global Impression of Improvement CI: Confidence Interval dpGAP: Database of Genotypes and Phenotypes IQR: Interquartile Range MECP2: Methyl-CpG-Binding Protein 2 N: Number NICHD: National Institute of Child Health and Development RNHS: Rett-related disorders Natural History Study RSBQ: Rett Syndrome Behavioral Questionnaire RTT: Rett syndrome SEM: Standard Error of the Mean Declarations Contributions JLN conceptualized this research, with input from AKP, TAB, EDM, SUP, and CF. JLN, AKP, TAB, EDM, SUP, and CF acquired the data. JLN designed the analysis, compiled and organized the data, and JLN and SKM conducted the analysis of the data. JLN, AKP, TAB, and EDM contributed to interpretation of the data. JLN prepared the draft of the manuscript with input from AKP, TAB, and EDM. All authors participated in reviewing, editing, and revising the initial draft. The authors read and approved the final submitted version. Funding This research was supported by funding from the National Institutes of Health grants U54HD061222 (AKP), P50HD103537 (JLN), UL1TR0030396 (the UAB Clinical Translational Research Center), UL1TR002243 (Vanderbilt University Medical Center Clinical Translational Research Center), the International Rett Syndrome Foundation (AKP, JLN), Children’s Hospital Colorado Foundation Ponzio Family Chair in Neurology Research (TAB), and the Vanderbilt University Annette Schaffer Eskind Endowed Chair (JLN). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Eunice Kennedy Shriver Child Health and Human Development Institute (NICHD). Availability of data and materials The datasets from the Rett syndrome and Rett-related Disorders Natural History Study (RNHS) have been deposited to the database of Genotypes and Phenotypes (dbGAP) repository per a predefined schedule at regular intervals (https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000574.v1.p1). Additionally, the datasets from the RNHS were transferred to the International Rett Syndrome Foundation to facilitate access based on reasonable request to [email protected] , pursuant to any required data transfer and use agreements. Ethics declarations Ethics and Consent to Participate The study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki. All participants or their legally authorized representatives provided written informed consent before participation in the study. The study was approved under a single-IRB provided by the University of Alabama, Birmingham Institutional Review Board (IRB #F150518001). A Certificate of Confidentiality was provided by the National Institute of Child Health and Development (NICHD). This work was not a clinical trial, but the non-interventional observational clinical study protocols were registered with Clinical Trials.Gov (NCT00299312, registration date 06 March 2006, and NCT02738281, registration date 22 November 2015). Consent for publication Not applicable. Competing interests JLN received research funding from the National Institutes of Health, the International Rett Syndrome Foundation, and Rett Syndrome Research Trust; clinical trials with Acadia Pharmaceuticals Inc., GW Pharmaceuticals, Ionis Pharmaceuticals, and Taysha Gene Therapies; consultancy paid to his institution from Taysha Gene Therapies; personal consultancy for Acadia Pharmaceuticals Inc., Alcyone Lifesciences, GW Pharmaceuticals, Hoffmann-La Roche, Jazz Pharmaceuticals, Neurogene, Ovid Therapeutics, and Signant Health; and participated on data safety monitoring boards for clinical trials conducted by Ovid Therapeutics and Ultragenyx. AKP received research funding from the National Institutes of Health, the International Rett Syndrome Foundation, and Rett Syndrome Research Trust; participated in clinical trials funded by Acadia Pharmaceuticals and is presently participating in gene therapy trials funded by Taysha Gene Therapies and Neurogene. He is chair of the Data Safety Monitoring Board for the Ionis trial (ION440-CS1) in MECP2 Duplication Syndrome. TAB received research funding from GRIN2B Foundation, the International Foundation for CDKL5 Research, Loulou Foundation, the National Institutes of Health, Rocky Mountain Rett Association, and Simons Foundation; consultancy for Alcyone, AveXis, GRIN Therapeutics, GW Pharmaceuticals, the International Rett Syndrome Foundation, Marinus Pharmaceuticals, Neurogene, Ovid Therapeutics, Takeda Pharmaceutical Company Limited and Taysha; clinical trials with Acadia Pharmaceuticals Inc., GW Pharmaceuticals, IONIS, Marinus Pharmaceuticals, Neurogene, Ovid Therapeutics, and Rett Syndrome Research Trust; all remuneration has been made to his department. EDM received research support from the National Institutes of Health, Penn Orphan Disease Center, the International Rett Syndrome Foundation, Rett Syndrome Research Trust, International CDKL5 Research Foundation, Department of Defense, and the Loulou Foundation. He has been a site principal investigator for trials from Stoke Therapeutics, SK Life, Ionis, Zogenix (now UCB), Acadia Pharmaceuticals Inc., Takeda Pharmaceuticals, Epygenix Pharmaceuticals, and Marinus Pharmaceuticals. He has received personal compensation for consulting and advisory board participation from Acadia, Ionis, Taysha, and Neurogene and the preparation of CME activities for Medscape. SUP received research funding from the National Institutes of Health, the MECP2 Duplication Foundation, and the ActiGraph Corporation. She has been a consultant for Ionis Pharmaceuticals and Taysha Gene Therapies. CF has been a site investigator for clinical trials with Acadia Pharmaceuticals, Zogenix, Ionis Pharmaceuticals, Taysha Gene Therapies, and Neurogene. He has received personal compensation for consulting from Acadia Pharmaceuticals and Taysha Gene Therapies. SKM has no conflicts of interest. References Gold WA, Percy AK, Neul JL, Cobb SR, Pozzo-Miller L, Issar JK, et al. Rett syndrome. Nat Rev Dis Primers. 2024;10(1):84. Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet. 1999;23(2):185–8. Neul JL, Benke TA, Marsh ED, Skinner SA, Merritt J, Lieberman DN, et al. The array of clinical phenotypes of males with mutations in Methyl-CpG binding protein 2. Am J Med Genet B Neuropsychiatr Genet. 2019;180(1):55–67. Thompson T, Gurfinkel D, Silveira L, Klamut N, Ferdinandsen K, Fu C, et al. Medical Biases and Misconceptions Impact Diagnoses in Males With Loss of Function MECP2 Variants. Am J Med Genet A. 2025;197(10):e64147. Hagberg B, Aicardi J, Dias K, Ramos O. A progressive syndrome of autism, dementia, ataxia, and loss of purposeful hand use in girls: Rett's syndrome: report of 35 cases. Ann Neurol. 1983;14(4):471–9. Neul JL, Kaufmann WE, Glaze DG, Christodoulou J, Clarke AJ, Bahi-Buisson N, et al. Rett syndrome: revised diagnostic criteria and nomenclature. Ann Neurol. 2010;68(6):944–50. Hagberg B, Witt-Engerstrom I. Rett syndrome: a suggested staging system for describing impairment profile with increasing age towards adolescence. Am J Med Genet Suppl. 1986;1:47–59. Collins BE, Neul JL. Rett Syndrome and MECP2 Duplication Syndrome: Disorders of MeCP2 Dosage. Neuropsychiatr Dis Treat. 2022;18:2813–35. Hagberg BA. Rett syndrome: clinical peculiarities, diagnostic approach, and possible cause. Pediatr Neurol. 1989;5(2):75–83. FitzGerald PM, Jankovic J, Glaze DG, Schultz R, Percy AK. Extrapyramidal involvement in Rett's syndrome. Neurology. 1990;40(2):293–5. Humphreys P, Barrowman N. The Incidence and Evolution of Parkinsonian Rigidity in Rett Syndrome: A Pilot Study. Can J Neurol Sci. 2016;43(4):567–73. Fehr S, Bebbington A, Ellaway C, Rowe P, Leonard H, Downs J. Altered attainment of developmental milestones influences the age of diagnosis of rett syndrome. J Child Neurol. 2011;26(8):980–7. Neul JL, Lane JB, Lee HS, Geerts S, Barrish JO, Annese F, et al. Developmental delay in Rett syndrome: data from the natural history study. J Neurodev Disord. 2014;6(1):20. Lee JY, Leonard H, Piek JP, Downs J. Early development and regression in Rett syndrome. Clin Genet. 2013;84(6):572–6. Einspieler C, Marschik PB. Regression in Rett syndrome: Developmental pathways to its onset. Neurosci Biobehav Rev. 2019;98:320–32. Guy J, Gan J, Selfridge J, Cobb S, Bird A. Reversal of neurological defects in a mouse model of Rett syndrome. Science. 2007;315(5815):1143–7. Lang M, Wither RG, Colic S, Wu C, Monnier PP, Bardakjian BL, et al. Rescue of behavioral and EEG deficits in male and female Mecp2-deficient mice by delayed Mecp2 gene reactivation. Hum Mol Genet. 2014;23(2):303–18. Percy AK, Ananth A, Neul JL. Rett Syndrome: The Emerging Landscape of Treatment Strategies. CNS Drugs. 2024;38(11):851–67. Percy AK, Benke TA, Marsh ED, Neul JL. Rett Syndrome: The Natural History Study Journey. Ann Child Neurol Soc. 2024;2(3):189–205. Neul JL, Benke TA, Marsh ED, Lane JB, Lieberman DN, Skinner SA, et al. Distribution of hand function by age in individuals with Rett syndrome. Ann Child Neurol Soc. 2023;1(3):228–38. Neul JL, Benke TA, Marsh ED, Suter B, Fu C, Ryther RC et al. Clinical Features and Disease Progression in Older Individuals with Rett Syndrome. Genes (Basel). 2024;15(8). Motil KJ, Geerts S, Annese F, Neul JL, Benke T, Marsh E, et al. Anthropometric Measures Correspond with Functional Motor Outcomes in Females with Rett Syndrome. J Pediatr. 2022;244:169–77. e3. Cutri-French C, Armstrong D, Saby J, Gorman C, Lane J, Fu C et al. Comparison of core features in four Developmental Encephalopathies in the Rett Natural History Study. Ann Neurol. 2020. Stallworth JL, Dy ME, Buchanan CB, Chen CF, Scott AE, Glaze DG, et al. Hand stereotypies: Lessons from the Rett Syndrome Natural History Study. Neurology. 2019;92(22):e2594–603. Buchanan CB, Stallworth JL, Joy AE, Dixon RE, Scott AE, Beisang AA, et al. Anxiety-like behavior and anxiolytic treatment in the Rett syndrome natural history study. J Neurodev Disord. 2022;14(1):31. Tarquinio DC, Hou W, Neul JL, Berkmen GK, Drummond J, Aronoff E, et al. The course of awake breathing disturbances across the lifespan in Rett syndrome. Brain Dev. 2018;40(7):515–29. Tarquinio DC, Hou W, Berg A, Kaufmann WE, Lane JB, Skinner SA, et al. Longitudinal course of epilepsy in Rett syndrome and related disorders. Brain. 2017;140(2):306–18. Killian JT, Lane JB, Cutter GR, Skinner SA, Kaufmann WE, Tarquinio DC, et al. Pubertal development in Rett syndrome deviates from typical females. Pediatr Neurol. 2014;51(6):769–75. Saby JN, Mulcahey PJ, Benke TA, Peters SU, Standridge SM, Lieberman DN, et al. Electroencephalographic Correlates of Clinical Severity in the Natural history study of RTT and Related Disorders. Ann Neurol. 2024;96(1):175–86. Saby JN, Peters SU, Benke TA, Standridge SM, Swanson LC, Lieberman DN, et al. Comparison of evoked potentials across four related developmental encephalopathies. J Neurodev Disord. 2023;15(1):10. Saby JN, Benke TA, Peters SU, Standridge SM, Matsuzaki J, Cutri-French C, et al. Multisite Study of Evoked Potentials in Rett Syndrome. Ann Neurol. 2021;89(4):790–802. Neul JL, Skinner SA, Annese F, Lane J, Heydemann P, Jones M, et al. Metabolic Signatures Differentiate Rett Syndrome From Unaffected Siblings. Front Integr Neurosci. 2020;14:7. Motil KJ, Barrish JO, Lane J, Geerts SP, Annese F, McNair L, et al. Vitamin d deficiency is prevalent in girls and women with rett syndrome. J Pediatr Gastroenterol Nutr. 2011;53(5):569–74. Raspa M, Gwaltney A, Bann C, von Hehn J, Benke TA, Marsh ED, et al. Psychometric Assessment of the Rett Syndrome Caregiver Assessment of Symptom Severity (RCASS). J Autism Dev Disord. 2025;55(3):997–1009. Neul JL, Benke TA, Marsh ED, Suter B, Silveira L, Fu C, et al. Top caregiver concerns in Rett syndrome and related disorders: data from the US natural history study. J Neurodev Disord. 2023;15(1):33. Raspa M, Bann CM, Gwaltney A, Benke TA, Fu C, Glaze DG, et al. A Psychometric Evaluation of the Motor-Behavioral Assessment Scale for Use as an Outcome Measure in Rett Syndrome Clinical Trials. Am J Intellect Dev Disabil. 2020;125(6):493–509. Lane JB, Salter AR, Jones NE, Cutter G, Horrigan J, Skinner SA, et al. Assessment of Caregiver Inventory for Rett Syndrome. J Autism Dev Disord. 2017;47(4):1102–12. Killian JT Jr., Lane JB, Lee HS, Pelham JH, Skinner SA, Kaufmann WE, et al. Caretaker Quality of Life in Rett Syndrome: Disorder Features and Psychological Predictors. Pediatr Neurol. 2016;58:67–74. Neul JL, Glaze DG, Percy AK, Feyma T, Beisang A, Dinh T, et al. Improving Treatment Trial Outcomes for Rett Syndrome: The Development of Rett-specific Anchors for the Clinical Global Impression Scale. J Child Neurol. 2015;30(13):1743–8. Lane JB, Lee HS, Smith LW, Cheng P, Percy AK, Glaze DG, et al. Clinical severity and quality of life in children and adolescents with Rett syndrome. Neurology. 2011;77(20):1812–8. Neul JL, Percy AK, Benke TA, Berry-Kravis EM, Glaze DG, Marsh ED, et al. Trofinetide for the treatment of Rett syndrome: a randomized phase 3 study. Nat Med. 2023;29(6):1468–75. Neul JL, Fang P, Barrish J, Lane J, Caeg EB, Smith EO, et al. Specific mutations in methyl-CpG-binding protein 2 confer different severity in Rett syndrome. Neurology. 2008;70(16):1313–21. Cuddapah VA, Pillai RB, Shekar KV, Lane JB, Motil KJ, Skinner SA, et al. Methyl-CpG-binding protein 2 (MECP2) mutation type is associated with disease severity in Rett syndrome. J Med Genet. 2014;51(3):152–8. Zubler JM, Wiggins LD, Macias MM, Whitaker TM, Shaw JS, Squires JK et al. Evidence-Informed Milestones for Developmental Surveillance Tools. Pediatrics. 2022;149(3). Percy AK, Neul JL, Ananth A, Benke TA, Marsh ED. Symptom Onset in Classic Rett Syndrome: Analysis of Initial Clinical Severity Scale Entries. Ann Child Neurol Soc; 2025. Tarquinio DC, Hou W, Neul JL, Lane JB, Barnes KV, O'Leary HM, et al. Age of diagnosis in Rett syndrome: patterns of recognition among diagnosticians and risk factors for late diagnosis. Pediatr Neurol. 2015;52(6):585–91. e2. Romano A, Rodocanachi Roidi ML, Savini MN, Vigano I, Dziubak M, Pietrogrande L et al. Effects of a Supervised-As-Needed Home Exercise Program on Scoliosis and Motor Function in Rett Syndrome: A Multiple-Baseline Study. J Clin Med. 2025;14(6). Capri T, Dovigo L, Semino M, Lotan M, Mohammadhasani N, Zamarra G, et al. Use of a low-tech tool in the improvement of social interaction of patients with Rett Syndrome: an observational study. Front Public Health. 2024;12:1353099. Kapel A, Kovacic T, Kos N, Velnar T. Impact of a 12-month multifaceted neurological physiotherapy intervention on gross motor function in women with Rett syndrome. J Integr Neurosci. 2022;21(2):59. Romano A, Ippolito E, Favetta M, Lotan M, Moran DS. Individualized Remotely Supervised Motor Activity Programs Promote Rehabilitation Goal Achievement, Motor Functioning, and Physical Activity of People with Rett Syndrome-A Single-Cohort Study. Int J Environ Res Public Health. 2022;20(1). Cass H, Reilly S, Owen L, Wisbeach A, Weekes L, Slonims V, et al. Findings from a multidisciplinary clinical case series of females with Rett syndrome. Dev Med Child Neurol. 2003;45(5):325–37. Larsson G, Lindstrom B, Engerstrom IW. Rett syndrome from a family perspective: The Swedish Rett Center survey. Brain Dev. 2005;27(Suppl 1):S14–9. Fehr S, Bebbington A, Nassar N, Downs J, Ronen GM. Trends in the diagnosis of Rett syndrome in Australia. Pediatr Res. 2011;70(3):313–9. Rett A. On a remarkable syndrome of cerebral atrophy associated with hyperammonaemia in childhood. Wien Med Wochenschr. 2016;166(11–12):322–4. Hagberg B, Goutieres F, Hanefeld F, Rett A, Wilson J. Rett syndrome: criteria for inclusion and exclusion. Brain Dev. 1985;7(3):372–3. Bisgaard AM, Schonewolf-Greulich B, Ravn K, Ronde G. Is it possible to diagnose Rett syndrome before classical symptoms become obvious? Review of 24 Danish cases born between 2003 and 2012. Eur J Paediatr Neurol. 2015;19(6):679–87. Einspieler C, Kerr AM, Prechtl HF. Abnormal general movements in girls with Rett disorder: the first four months of life. Brain Dev. 2005;27(Suppl 1):S8–13. Einspieler C, Sigafoos J, Bolte S, Bratl-Pokorny KD, Landa R, Marschik PB. Highlighting the first 5 months of life: General movements in infants later diagnosed with autism spectrum disorder or Rett Syndrome. Res Autism Spectr Disord. 2014;8(3):286–91. Einspieler C, Freilinger M, Marschik PB. Behavioural biomarkers of typical Rett syndrome: moving towards early identification. Wien Med Wochenschr. 2016;166(11–12):333–7. Suter B, Treadwell-Deering D, Zoghbi HY, Glaze DG, Neul JL. Brief Report: MECP2 Mutations in People Without Rett Syndrome. J Autism Dev Disord. 2013. Foley KR, Downs J, Bebbington A, Jacoby P, Girdler S, Kaufmann WE, et al. Change in gross motor abilities of girls and women with rett syndrome over a 3- to 4-year period. J Child Neurol. 2011;26(10):1237–45. Bisgaard AM, Wong K, Hojfeldt AK, Larsen JL, Schonewolf-Greulich B, Ronde G, et al. Decline in gross motor skills in adult Rett syndrome; results from a Danish longitudinal study. Am J Med Genet A. 2021;185(12):3683–93. Hagberg B. Clinical manifestations and stages of Rett syndrome. Ment Retard Dev Disabil Res Rev. 2002;8(2):61–5. Percy AK, Neul JL, Benke TA, Marsh ED, Glaze DG. A review of the Rett Syndrome Behaviour Questionnaire and its utilization in the assessment of symptoms associated with Rett syndrome. Front Pediatr. 2023;11:1229553. Downs J, Wong K, Leonard H. Associations between genotype, phenotype and behaviours measured by the Rett syndrome behaviour questionnaire in Rett syndrome. J Neurodev Disord. 2024;16(1):59. Kaufmann WE, Oberman LM, Downs J, Leonard H, Barnes KV. Rett Syndrome Behaviour Questionnaire: Variability of Scores and Related Factors. J Child Adolesc Psychopharmacol. 2025;35(7):388–98. Administration FaD. Patient-Focused Drug Development: Incorporating Clinical Outcome Assessments Into Endpoints for Regulatory Decision-Making, draft guidance. In: Services UDoHaH, editor. 2023. Connor-Ahmad S, Tjeertes J, Chladek M, Newton L, Symonds T, Clinch S, et al. Developing Angelman syndrome-specific clinician-reported and caregiver-reported measures to support holistic, patient-centered drug development. Orphanet J Rare Dis. 2023;18(1):156. Gizzo L, Bliss G, Palaty C, Kolevzon A. Caregiver perspectives on patient-focused drug development for Phelan-McDermid syndrome. Orphanet J Rare Dis. 2024;19(1):134. Downs J, Ludwig NN, Wojnaroski M, Keeley J, Schust Myers L, Chapman CAT, et al. What does better look like in individuals with severe neurodevelopmental impairments? A qualitative descriptive study on SCN2A-related developmental and epileptic encephalopathy. Qual Life Res. 2024;33(2):519–28. Hecker J, Conecker G, Chapman C, Hommer R, Ludwig NN, Sevinc G, et al. Patient-advocate-led global coalition adapting fit-for-purpose outcomes measures to assure meaningful inclusion of DEEs in clinical trials. Ther Adv Rare Dis. 2024;18:26330040241249762. Downs J, Haywood S, Ludwig NN, Wojnaroski M, Hommer R, Muzyczka K et al. Caregiver-reported meaningful change in functional domains for individuals with developmental and epileptic encephalopathy: A convergent mixed-methods design. Dev Med Child Neurol. 2025. Keeley J, Skoda Z, Utley K, Marsh ED, Conecker GA, Hecker J et al. Parent/caregiver perspectives of meaningful improvement in functional domains for people with CDKL5 deficiency disorder: a mixed-methods study. Qual Life Res. 2025. Pokorny FB, Schmitt M, Egger M, Bartl-Pokorny KD, Zhang D, Schuller BW, et al. Automatic vocalisation-based detection of fragile X syndrome and Rett syndrome. Sci Rep. 2022;12(1):13345. Marschik PB, Lemcke S, Einspieler C, Zhang D, Bolte S, Townend GS, et al. Early development in Rett syndrome - the benefits and difficulties of a birth cohort approach. Dev Neurorehabil. 2018;21(1):68–72. Additional Declarations Competing interest reported. JLN received research funding from the National Institutes of Health, the International Rett Syndrome Foundation, and Rett Syndrome Research Trust; clinical trials with Acadia Pharmaceuticals Inc., GW Pharmaceuticals, Ionis Pharmaceuticals, and Taysha Gene Therapies; consultancy paid to his institution from Taysha Gene Therapies; personal consultancy for Acadia Pharmaceuticals Inc., Alcyone Lifesciences, GW Pharmaceuticals, Hoffmann-La Roche, Jazz Pharmaceuticals, Neurogene, Ovid Therapeutics, and Signant Health; and participated on data safety monitoring boards for clinical trials conducted by Ovid Therapeutics and Ultragenyx. AKP received research funding from the National Institutes of Health, the International Rett Syndrome Foundation, and Rett Syndrome Research Trust; participated in clinical trials funded by Acadia Pharmaceuticals and is presently participating in gene therapy trials funded by Taysha Gene Therapies and Neurogene. He is chair of the Data Safety Monitoring Board for the Ionis trial (ION440-CS1) in MECP2 Duplication Syndrome. TAB received research funding from GRIN2B Foundation, the International Foundation for CDKL5 Research, Loulou Foundation, the National Institutes of Health, Rocky Mountain Rett Association, and Simons Foundation; consultancy for Alcyone, AveXis, GRIN Therapeutics, GW Pharmaceuticals, the International Rett Syndrome Foundation, Marinus Pharmaceuticals, Neurogene, Ovid Therapeutics, Takeda Pharmaceutical Company Limited and Taysha; clinical trials with Acadia Pharmaceuticals Inc., GW Pharmaceuticals, IONIS, Marinus Pharmaceuticals, Neurogene, Ovid Therapeutics, and Rett Syndrome Research Trust; all remuneration has been made to his department. EDM received research support from the National Institutes of Health, Penn Orphan Disease Center, the International Rett Syndrome Foundation, Rett Syndrome Research Trust, International CDKL5 Research Foundation, Department of Defense, and the Loulou Foundation. He has been a site principal investigator for trials from Stoke Therapeutics, SK Life, Ionis, Zogenix (now UCB), Acadia Pharmaceuticals Inc., Takeda Pharmaceuticals, Epygenix Pharmaceuticals, and Marinus Pharmaceuticals. He has received personal compensation for consulting and advisory board participation from Acadia, Ionis, Taysha, and Neurogene and the preparation of CME activities for Medscape. SUP received research funding from the National Institutes of Health, the MECP2 Duplication Foundation, and the ActiGraph Corporation. She has been a consultant for Ionis Pharmaceuticals and Taysha Gene Therapies. CF has been a site investigator for clinical trials with Acadia Pharmaceuticals, Zogenix, Ionis Pharmaceuticals, Taysha Gene Therapies, and Neurogene. He has received personal compensation for consulting from Acadia Pharmaceuticals and Taysha Gene Therapies. SKM has no conflicts of interest. Supplementary Files AddFile1TableS1.pdf Supplementary Information Additional file 1: Table S1 Demographic Information. AddFile1TableS1.pdf AddFile2TableS2.pdf Additional file 2: Table S2 MECP2 Mutation Frequency. AddFile2TableS2.pdf AddFile3TableS3.pdf Additional file 3: Table S3: Developmental skill mapping between protocols 5201 and 5211. AddFile3TableS3.pdf AddFile4SupplementalMethods.pdf Additional file 4: Supplemental Methods. AddFile4SupplementalMethods.pdf AddFile5FigureS1.pdf Additional file 5: Figure S1: Cumulative incidence curves of skill gain. AddFile5FigureS1.pdf AddFile6FigureS2.pdf Additional file 6: Figure S2: Cumulative incidence curves of skill loss. AddFile6FigureS1.pdf AddFile7FigureS3.pdf Additional file 7: Figure S3: Cumulative incidence curves of skill gain to loss. AddFile7FigureS3.pdf AddFile8FigureS4.pdf Additional file 8: Figure S4: Cumulative incidence curves of age of skill regain. AddFile8FigureS4.pdf AddFile9FigureS5.pdf Additional file 9: Figure S5: Cumulative incidence curves of time from skill loss to regain. AddFile9FigureS5.pdf Cite Share Download PDF Status: Published Journal Publication published 12 Mar, 2026 Read the published version in Journal of Neurodevelopmental Disorders → Version 1 posted Editorial decision: Revision requested 05 Feb, 2026 Reviews received at journal 05 Feb, 2026 Reviewers agreed at journal 20 Jan, 2026 Reviews received at journal 16 Jan, 2026 Reviewers agreed at journal 12 Jan, 2026 Reviewers invited by journal 09 Dec, 2025 Editor assigned by journal 03 Dec, 2025 Submission checks completed at journal 03 Dec, 2025 First submitted to journal 30 Nov, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8245192","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":557725721,"identity":"883a1eab-bcef-44e6-8eaf-fb8b28fae498","order_by":0,"name":"Jeffrey L. Neul","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9ElEQVRIiWNgGAWjYBACxgbGBx9ADD4wt8CGGC3MhjNADDYw1yCNGHtQtRwmQkN7M2NzRcVhoBbeg495DM4nbrh2+AHDxz21uB3Wc5ix8cwZkBa+ZGMeg9uJG26nGTDOeHYct5YZ+ccfNraBtPCYSQO1GBvczmFg5jlwDLeW+Y8ZGxv/gbWY/+YxOEeElhnMQC0NEFuYeQwOyEG11ODxSzJjY8OxdB42Zh5jyTkGyXKSQL8cnHHgAE4thu1A7zfUWMvxs/cYfnhTYcfDdzv54YMPB+pwa2kAU808DMxIokArcEeQPITCNBO3LaNgFIyCUTDiAAAHE1BW9a4Y9gAAAABJRU5ErkJggg==","orcid":"","institution":"Vanderbilt University Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Jeffrey","middleName":"L.","lastName":"Neul","suffix":""},{"id":557725723,"identity":"35155cc4-56fc-4dc8-966b-c94160ee14cd","order_by":1,"name":"Timothy A. Benke","email":"","orcid":"","institution":"Children’s Hospital of Colorado and University of Colorado","correspondingAuthor":false,"prefix":"","firstName":"Timothy","middleName":"A.","lastName":"Benke","suffix":""},{"id":557725726,"identity":"b8df5e32-2506-4495-80da-6b914eec294c","order_by":2,"name":"Eric D. Marsh","email":"","orcid":"","institution":"University of Pennsylvania Perelman School of Medicine and Children’s Hospital of Philadelphia","correspondingAuthor":false,"prefix":"","firstName":"Eric","middleName":"D.","lastName":"Marsh","suffix":""},{"id":557725729,"identity":"afa5dc99-8709-4768-8cfd-af13eb4fd64e","order_by":3,"name":"Sarika U. Peters","email":"","orcid":"","institution":"Vanderbilt University Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Sarika","middleName":"U.","lastName":"Peters","suffix":""},{"id":557725733,"identity":"0c0a6c57-a638-4778-a844-9d279f12fb40","order_by":4,"name":"Cary Fu","email":"","orcid":"","institution":"Vanderbilt University Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Cary","middleName":"","lastName":"Fu","suffix":""},{"id":557725735,"identity":"acc238ac-2387-439c-9f2e-beeea08a6ad5","order_by":5,"name":"Jonathan K. Merritt","email":"","orcid":"","institution":"Vanderbilt University Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Jonathan","middleName":"K.","lastName":"Merritt","suffix":""},{"id":557725736,"identity":"d56a197a-c148-49d9-97c7-cf7bb5052ba1","order_by":6,"name":"Alan K. Percy","email":"","orcid":"","institution":"University of Alabama at Birmingham","correspondingAuthor":false,"prefix":"","firstName":"Alan","middleName":"K.","lastName":"Percy","suffix":""}],"badges":[],"createdAt":"2025-12-01 02:08:24","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8245192/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8245192/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s11689-026-09680-6","type":"published","date":"2026-03-12T15:59:51+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":98431515,"identity":"023a2fda-7c36-4d47-bb8c-3b31b970dc43","added_by":"auto","created_at":"2025-12-17 16:47:50","extension":"png","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":328746,"visible":true,"origin":"","legend":"","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/e99884acf1a27fb0d390c0a8.png"},{"id":98180938,"identity":"db06939e-f276-4d6d-bcd6-85fc192c68ea","added_by":"auto","created_at":"2025-12-15 01:08:24","extension":"png","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":545003,"visible":true,"origin":"","legend":"","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/223f286ff31fc67847dc3e8b.png"},{"id":98181006,"identity":"cd931515-b089-4067-9ecb-99d8c8957466","added_by":"auto","created_at":"2025-12-15 01:08:34","extension":"png","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":561387,"visible":true,"origin":"","legend":"","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/4f8812447dec8eec3fcdc4dc.png"},{"id":98431761,"identity":"022ecfdb-7255-462e-bec9-d894527de34a","added_by":"auto","created_at":"2025-12-17 16:48:18","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":6532633,"visible":true,"origin":"","legend":"","description":"","filename":"20251202DevMilestoneManuscriptDraftCLEAN.docx","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/a4a9b0b3ec1152231c6f9af5.docx"},{"id":98180940,"identity":"5024a268-ceaa-406b-8f76-56f705b08f96","added_by":"auto","created_at":"2025-12-15 01:08:24","extension":"png","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":448764,"visible":true,"origin":"","legend":"","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/5369838a32048b26c419a687.png"},{"id":98180934,"identity":"c574c4d6-4d0f-4191-af68-f663d055ad91","added_by":"auto","created_at":"2025-12-15 01:08:23","extension":"docx","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":27414,"visible":true,"origin":"","legend":"","description":"","filename":"Table1JNDWord.docx","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/62037dbc2883f614816f4949.docx"},{"id":98180944,"identity":"c7090213-d417-4528-812a-a142a145b41e","added_by":"auto","created_at":"2025-12-15 01:08:25","extension":"docx","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":26352,"visible":true,"origin":"","legend":"","description":"","filename":"Table2JNDWord.docx","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/2ddd3db3b642bc1afbab7d9e.docx"},{"id":98180953,"identity":"78c8050b-e034-430f-8e6b-8d8d4e1cc55a","added_by":"auto","created_at":"2025-12-15 01:08:26","extension":"docx","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":28435,"visible":true,"origin":"","legend":"","description":"","filename":"Table3JNDWord.docx","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/19860c42c109b48c14360133.docx"},{"id":98432053,"identity":"0977c6fb-c461-4c6c-ac53-150d7c38ad09","added_by":"auto","created_at":"2025-12-17 16:48:53","extension":"json","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":12305,"visible":true,"origin":"","legend":"","description":"","filename":"0b1e03de5a314715892616601331fe93.json","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/7ffca2abf2b5ba5ec7596429.json"},{"id":98180937,"identity":"866cc625-04d7-49ae-967c-8e2219745a47","added_by":"auto","created_at":"2025-12-15 01:08:24","extension":"pdf","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":59517,"visible":true,"origin":"","legend":"","description":"","filename":"AddFile1TableS1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/11b86362331f710def55c527.pdf"},{"id":98180966,"identity":"95e7ca56-8822-4ec8-95af-e958974b3d69","added_by":"auto","created_at":"2025-12-15 01:08:28","extension":"pdf","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":72676,"visible":true,"origin":"","legend":"","description":"","filename":"AddFile2TableS2.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/f938298a90ca7b677a64ca26.pdf"},{"id":98180968,"identity":"f9b037ce-03c3-48b2-89c6-42000aba28c8","added_by":"auto","created_at":"2025-12-15 01:08:28","extension":"pdf","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":105861,"visible":true,"origin":"","legend":"","description":"","filename":"AddFile3TableS3.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/7db8966381f7fbf4d6f5ed59.pdf"},{"id":98180906,"identity":"544d5122-f216-48ae-883b-515ae2efdb0c","added_by":"auto","created_at":"2025-12-15 01:08:12","extension":"pdf","order_by":12,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":138646,"visible":true,"origin":"","legend":"","description":"","filename":"AddFile4SupplementalMethods.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/bba5d6bcf55fc5c86abbe28a.pdf"},{"id":98181007,"identity":"d8470c8f-7352-45d1-820a-a2dc27e670a6","added_by":"auto","created_at":"2025-12-15 01:08:34","extension":"pdf","order_by":13,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1807057,"visible":true,"origin":"","legend":"","description":"","filename":"AddFile5FigureS1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/21cbb91353fb682e0acc79b0.pdf"},{"id":98180969,"identity":"f08cbb41-ad71-4c00-9a1f-a9319afefbc2","added_by":"auto","created_at":"2025-12-15 01:08:28","extension":"pdf","order_by":14,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1766110,"visible":true,"origin":"","legend":"","description":"","filename":"AddFile6FigureS2.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/168525400ecdf99b918a1c9e.pdf"},{"id":98180936,"identity":"76ef82e5-69ce-4f99-a806-3e47d960b884","added_by":"auto","created_at":"2025-12-15 01:08:24","extension":"pdf","order_by":15,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1892444,"visible":true,"origin":"","legend":"","description":"","filename":"AddFile7FigureS3.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/6e1b70b0b75352d8b9b1f1bc.pdf"},{"id":98180961,"identity":"3060ea8e-a126-44cd-b15c-401f4ab2d509","added_by":"auto","created_at":"2025-12-15 01:08:27","extension":"pdf","order_by":16,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1657576,"visible":true,"origin":"","legend":"","description":"","filename":"AddFile8FigureS4.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/cc925311c5c0e6736a015842.pdf"},{"id":98181031,"identity":"8120007e-b8c2-4e94-b5f8-3c42b15d4e54","added_by":"auto","created_at":"2025-12-15 01:08:36","extension":"pdf","order_by":17,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1896963,"visible":true,"origin":"","legend":"","description":"","filename":"AddFile9FigureS5.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/a5dd3edf8b439a2bd31562bf.pdf"},{"id":98180955,"identity":"33b4f7bc-f7da-41fb-9f5d-dafd3c01d59a","added_by":"auto","created_at":"2025-12-15 01:08:26","extension":"xml","order_by":18,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":426673,"visible":true,"origin":"","legend":"","description":"","filename":"0b1e03de5a314715892616601331fe931enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/abf34b2cd4f3794a819a6b83.xml"},{"id":98180964,"identity":"7d329b57-beb2-4ab1-a4fd-f761b8612d87","added_by":"auto","created_at":"2025-12-15 01:08:28","extension":"png","order_by":19,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":328746,"visible":true,"origin":"","legend":"","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/2db14e8c96a9b7c798eabc0b.png"},{"id":98180965,"identity":"6c763e97-c3eb-4517-a143-939b0ed45bc0","added_by":"auto","created_at":"2025-12-15 01:08:28","extension":"png","order_by":20,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":545003,"visible":true,"origin":"","legend":"","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/58254b6b20a860f71c7b0091.png"},{"id":98181005,"identity":"a1c6cca4-79c1-4bf0-a541-c2e87d16f69a","added_by":"auto","created_at":"2025-12-15 01:08:34","extension":"png","order_by":21,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":561387,"visible":true,"origin":"","legend":"","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/659c760afd5faf16c8418419.png"},{"id":98180929,"identity":"722f9663-5fc3-4f8d-9ba3-20bc7cef1d26","added_by":"auto","created_at":"2025-12-15 01:08:21","extension":"png","order_by":22,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":448764,"visible":true,"origin":"","legend":"","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/b6f1da59691d4812af0e66c0.png"},{"id":98180948,"identity":"677aa7c4-7ebf-42d4-8663-a4f358fd5087","added_by":"auto","created_at":"2025-12-15 01:08:25","extension":"emf","order_by":23,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":5277496,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage1.emf","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/973067afe2404bad03f6be68.emf"},{"id":98181029,"identity":"4b4f4ab9-a9e1-440f-ac87-1b27a09eac45","added_by":"auto","created_at":"2025-12-15 01:08:36","extension":"emf","order_by":24,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":7092712,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage2.emf","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/ac7a47e4d265c01d05d7c2ad.emf"},{"id":98180999,"identity":"0919f763-dc86-4e91-8f95-e305725cf670","added_by":"auto","created_at":"2025-12-15 01:08:33","extension":"emf","order_by":25,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":7050300,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage3.emf","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/238ff7735b4f81c8b73a1b01.emf"},{"id":98181021,"identity":"7df9ceaa-03b6-49f5-8e11-db3de4c8a715","added_by":"auto","created_at":"2025-12-15 01:08:35","extension":"jpeg","order_by":26,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1775093,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/c4de7ccc14cb2645fdc29aa7.jpeg"},{"id":98180952,"identity":"711c67e5-4e9c-4453-87c9-f0b7d2a068a4","added_by":"auto","created_at":"2025-12-15 01:08:26","extension":"png","order_by":27,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":53256,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure1.png","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/3f8afec8ab00980bdca9680c.png"},{"id":98180942,"identity":"498e1656-31a5-4240-ae2e-6f3eb9ad9ab4","added_by":"auto","created_at":"2025-12-15 01:08:24","extension":"png","order_by":28,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":87308,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure2.png","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/bdfc535d4c33f28047255188.png"},{"id":98180963,"identity":"175e17cc-e4eb-4cb2-846f-23052f857c39","added_by":"auto","created_at":"2025-12-15 01:08:28","extension":"png","order_by":29,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":89552,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure3.png","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/1abefb680c5ffffab521f257.png"},{"id":98180931,"identity":"ca70b427-682a-4520-8cd7-b5c0752dc64b","added_by":"auto","created_at":"2025-12-15 01:08:22","extension":"png","order_by":30,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":101425,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure4.png","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/67224a072b9671ebf60ccbb9.png"},{"id":98180958,"identity":"9ae35cc1-5149-402e-b4eb-9560bda3eb7a","added_by":"auto","created_at":"2025-12-15 01:08:27","extension":"png","order_by":31,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":54356,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/44aa76417c0a51fcc4ef08e9.png"},{"id":98180949,"identity":"932ec37e-7b1d-4cdb-b2a8-fce3b12f7ad5","added_by":"auto","created_at":"2025-12-15 01:08:25","extension":"png","order_by":32,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":86264,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/3921a2138d08338683ff8dea.png"},{"id":98180933,"identity":"cde85332-4ef8-4e6d-8cbb-2cb66e4d67da","added_by":"auto","created_at":"2025-12-15 01:08:22","extension":"png","order_by":33,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":88279,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/2e6cd9db05d36ebba4ff806e.png"},{"id":98180951,"identity":"f60f5d5b-8e6c-4823-884c-d3296b205176","added_by":"auto","created_at":"2025-12-15 01:08:26","extension":"png","order_by":34,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":333128,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/869722afeedcec6767460b00.png"},{"id":98181023,"identity":"f37bfba7-8e39-486d-93ff-290ebd34cd33","added_by":"auto","created_at":"2025-12-15 01:08:36","extension":"xml","order_by":35,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":424024,"visible":true,"origin":"","legend":"","description":"","filename":"0b1e03de5a314715892616601331fe931structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/742c7bb0dfdc207973f90c5b.xml"},{"id":98431420,"identity":"82f16f74-582f-4d2a-bbb2-ef3ce7c90560","added_by":"auto","created_at":"2025-12-17 16:47:39","extension":"html","order_by":36,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":443553,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/2dae0c2c4c6a3954048256d7.html"},{"id":98180943,"identity":"2c661863-da1f-43cd-a4ed-c380bdc30da9","added_by":"auto","created_at":"2025-12-15 01:08:25","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":328746,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCumulative incident of gain for representative skills.\u003c/strong\u003e Cumulative incidence curves for age of skill gain are shown for skills representing gross motor (A), fine motor (B), expressive communication (C), receptive communication (D), and social/adaptive (E) skill domains. The colors for each representative skill are shown in the legend, with censored data points shown as cross lines, a colored vertical line for the median age of gain for that specific skill, wide spaced dashed vertical line is at 4 years of age and closely spaced dashed vertical line is at 6 years of age in all graphs.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/98e9c84304e6ea68711dc3e4.png"},{"id":98180945,"identity":"ff1c38e7-2c37-49f5-881e-a2e215c9235f","added_by":"auto","created_at":"2025-12-15 01:08:25","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":545003,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCumulative incident of loss and time from gain to loss for representative skills.\u003c/strong\u003e Cumulative incidence curves for age of skill loss are shown for skills representing gross motor (A), fine motor (B), expressive communication (C), receptive communication (D), and social/adaptive (E) skill domains. The age of skill loss is displayed in panels A1, B1, C1, D1, and E1, colors for each representative skill are shown in the legend, with censored data points shown as cross lines, a colored vertical line for the median age of loss for that specific skill. The time from gain to loss is displayed in panels A2, B2, C2, D2, and E2, with a colored vertical line for the median time of gain to loss for that particular skill.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/a119b2a7bf1c2840d18ac2b9.png"},{"id":98180946,"identity":"24b3c377-aa7d-4cdb-894e-6ac10410d5a2","added_by":"auto","created_at":"2025-12-15 01:08:25","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":561387,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCumulative incident of regain and time from loss to regain for representative skills.\u003c/strong\u003e Cumulative incidence curves for age of skill regain or time from loss to regain are shown for skills representing gross motor (A), fine motor (B), expressive communication (C), receptive communication (D), and social/adaptive (E) skill domains. The age of skill regain is displayed in panels A1, B1, C1, D1, and E1, with colors for each representative skill shown in the legend, censored data points are shown as cross lines, a colored vertical line for the median age of regain for that specific skill, and a closely-spaced black dashed line demarking 6 years of age in all graphs. The time from loss to regain is displayed in panels A2, B2, C2, D2, and E2, with a colored vertical line for the median time of loss to regain for that particular skill, and a closely spaced black vertical line demarking 2 years from loss to regain in all graphs.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/d117521010904f475b1aa808.png"},{"id":98181003,"identity":"844913b1-6b63-43c3-8f36-53b8ac1ff555","added_by":"auto","created_at":"2025-12-15 01:08:34","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":448764,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eOne-year interval incidence of skill gain/regain for individual skills and for any one skill. \u003c/strong\u003eThe percentage (%) of participants eligible within one-year age intervals who gained or regained a specific skill is shown, as well as the percentage of eligible participants within the age bin who gained at least 1 skill out of all 51 skills characterized or at least 1 skill out of a restricted subset of 38 skills. Grey highlighted skills identify those skills not included in the restricted subset of 38 skills. The heatmap color coding shown at the bottom, with white for 0%, yellow for 5%, and dark green for 100%.\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/679b9b136649e1bad88f9629.png"},{"id":104739711,"identity":"5ade33d6-9dff-42b3-a736-f81712adbee2","added_by":"auto","created_at":"2026-03-16 16:12:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3894433,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/49c6fbd2-ab0d-4b36-9160-16f2fd69ca51.pdf"},{"id":98180947,"identity":"41ed66ff-a740-4be5-88fb-726214d6f66d","added_by":"auto","created_at":"2025-12-15 01:08:25","extension":"pdf","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":59517,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary Information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAdditional file 1: Table S1 Demographic Information. \u0026nbsp;AddFile1TableS1.pdf\u003c/p\u003e","description":"","filename":"AddFile1TableS1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/7201f09a6b852310a295d740.pdf"},{"id":98180930,"identity":"8cda6c31-023f-4554-a9d2-2fca2b99da90","added_by":"auto","created_at":"2025-12-15 01:08:22","extension":"pdf","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":72676,"visible":true,"origin":"","legend":"\u003cp\u003eAdditional file 2: Table S2 MECP2 Mutation Frequency. \u0026nbsp;AddFile2TableS2.pdf\u003c/p\u003e","description":"","filename":"AddFile2TableS2.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/23bdeb9ee24546477142c082.pdf"},{"id":98181017,"identity":"d38cacf4-5aa4-43a6-9f30-9fe563df8df1","added_by":"auto","created_at":"2025-12-15 01:08:35","extension":"pdf","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":105861,"visible":true,"origin":"","legend":"\u003cp\u003eAdditional file 3: Table S3: Developmental skill mapping between protocols 5201 and 5211. AddFile3TableS3.pdf\u003c/p\u003e","description":"","filename":"AddFile3TableS3.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/5a75974d97a76dc1fa604943.pdf"},{"id":98180941,"identity":"7a45bc9e-92bd-4018-8086-d6602a682162","added_by":"auto","created_at":"2025-12-15 01:08:24","extension":"pdf","order_by":7,"title":"","display":"","copyAsset":false,"role":"supplement","size":138646,"visible":true,"origin":"","legend":"\u003cp\u003eAdditional file 4: Supplemental Methods. AddFile4SupplementalMethods.pdf\u003c/p\u003e","description":"","filename":"AddFile4SupplementalMethods.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/6c4dd15aaa2c26882a7404c4.pdf"},{"id":98180957,"identity":"c544087f-03d3-452d-88c1-fade3961397f","added_by":"auto","created_at":"2025-12-15 01:08:27","extension":"pdf","order_by":8,"title":"","display":"","copyAsset":false,"role":"supplement","size":1807057,"visible":true,"origin":"","legend":"\u003cp\u003eAdditional file 5: Figure S1: Cumulative incidence curves of skill gain. AddFile5FigureS1.pdf\u003c/p\u003e","description":"","filename":"AddFile5FigureS1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/e7907418d7db26661632779a.pdf"},{"id":98180939,"identity":"6346ded7-a5f8-4007-bb04-8bc3419d1223","added_by":"auto","created_at":"2025-12-15 01:08:24","extension":"pdf","order_by":9,"title":"","display":"","copyAsset":false,"role":"supplement","size":1766110,"visible":true,"origin":"","legend":"\u003cp\u003eAdditional file 6: Figure S2: Cumulative incidence curves of skill loss. AddFile6FigureS1.pdf\u003c/p\u003e","description":"","filename":"AddFile6FigureS2.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/d13f70827f8f4b244a7bfae9.pdf"},{"id":98430700,"identity":"30bcae87-d5f3-4b3a-b5d7-4df4f51450ff","added_by":"auto","created_at":"2025-12-17 16:46:05","extension":"pdf","order_by":10,"title":"","display":"","copyAsset":false,"role":"supplement","size":1892444,"visible":true,"origin":"","legend":"\u003cp\u003eAdditional file 7: Figure S3: Cumulative incidence curves of skill gain to loss. AddFile7FigureS3.pdf\u003c/p\u003e","description":"","filename":"AddFile7FigureS3.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/148682929bb3a657deee2ba3.pdf"},{"id":98180932,"identity":"9cf283ea-5439-4f82-9b7f-52a84e88aca5","added_by":"auto","created_at":"2025-12-15 01:08:22","extension":"pdf","order_by":11,"title":"","display":"","copyAsset":false,"role":"supplement","size":1657576,"visible":true,"origin":"","legend":"\u003cp\u003eAdditional file 8: Figure S4: Cumulative incidence curves of age of skill regain. AddFile8FigureS4.pdf\u003c/p\u003e","description":"","filename":"AddFile8FigureS4.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/cf7825ef7dfbbf95827cc523.pdf"},{"id":98180956,"identity":"b78260a1-f285-4f01-abcc-08ea3f9da85d","added_by":"auto","created_at":"2025-12-15 01:08:27","extension":"pdf","order_by":12,"title":"","display":"","copyAsset":false,"role":"supplement","size":1896963,"visible":true,"origin":"","legend":"\u003cp\u003eAdditional file 9: Figure S5: Cumulative incidence curves of time from skill loss to regain. AddFile9FigureS5.pdf\u003c/p\u003e","description":"","filename":"AddFile9FigureS5.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8245192/v1/e5474cf8ac6e373e196aa2fd.pdf"}],"financialInterests":"Competing interest reported. JLN received research funding from the National Institutes of Health, the International Rett Syndrome Foundation, and Rett Syndrome Research Trust; clinical trials with Acadia Pharmaceuticals Inc., GW Pharmaceuticals, Ionis Pharmaceuticals, and Taysha Gene Therapies; consultancy paid to his institution from Taysha Gene Therapies; personal consultancy for Acadia Pharmaceuticals Inc., Alcyone Lifesciences, GW Pharmaceuticals, Hoffmann-La Roche, Jazz Pharmaceuticals, Neurogene, Ovid Therapeutics, and Signant Health; and participated on data safety monitoring boards for clinical trials conducted by Ovid Therapeutics and Ultragenyx.\n\nAKP received research funding from the National Institutes of Health, the International Rett Syndrome Foundation, and Rett Syndrome Research Trust; participated in clinical trials funded by Acadia Pharmaceuticals and is presently participating in gene therapy trials funded by Taysha Gene Therapies and Neurogene. He is chair of the Data Safety Monitoring Board for the Ionis trial (ION440-CS1) in MECP2 Duplication Syndrome.\n\nTAB received research funding from GRIN2B Foundation, the International Foundation for CDKL5 Research, Loulou Foundation, the National Institutes of Health, Rocky Mountain Rett Association, and Simons Foundation; consultancy for Alcyone, AveXis, GRIN Therapeutics, GW Pharmaceuticals, the International Rett Syndrome Foundation, Marinus Pharmaceuticals, Neurogene, Ovid Therapeutics, Takeda Pharmaceutical Company Limited and Taysha; clinical trials with Acadia Pharmaceuticals Inc., GW Pharmaceuticals, IONIS, Marinus Pharmaceuticals, Neurogene, Ovid Therapeutics, and Rett Syndrome Research Trust; all remuneration has been made to his department.\n\nEDM received research support from the National Institutes of Health, Penn Orphan Disease Center, the International Rett Syndrome Foundation, Rett Syndrome Research Trust, International CDKL5 Research Foundation, Department of Defense, and the Loulou Foundation. He has been a site principal investigator for trials from Stoke Therapeutics, SK Life, Ionis, Zogenix (now UCB), Acadia Pharmaceuticals Inc., Takeda Pharmaceuticals, Epygenix Pharmaceuticals, and Marinus Pharmaceuticals. He has received personal compensation for consulting and advisory board participation from Acadia, Ionis, Taysha, and Neurogene and the preparation of CME activities for Medscape.\n\nSUP received research funding from the National Institutes of Health, the MECP2 Duplication Foundation, and the ActiGraph Corporation. She has been a consultant for Ionis Pharmaceuticals and Taysha Gene Therapies.\n\nCF has been a site investigator for clinical trials with Acadia Pharmaceuticals, Zogenix, Ionis Pharmaceuticals, Taysha Gene Therapies, and Neurogene. He has received personal compensation for consulting from Acadia Pharmaceuticals and Taysha Gene Therapies.\n\nSKM has no conflicts of interest.","formattedTitle":"Trajectory of skill acquisition, loss, and regain in females with classic Rett syndrome","fulltext":[{"header":"Introduction","content":"\u003cp\u003eRett syndrome (RTT) is a rare neurodevelopmental disorder primarily caused by pathogenic variants in \u003cem\u003eMethyl-CpG-Binding Protein 2\u003c/em\u003e (\u003cem\u003eMECP2\u003c/em\u003e) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. RTT primarily, but not exclusively, affects females [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] and has a characteristic disease pattern with \u0026ldquo;normal\u0026rdquo; initial development, followed by developmental delay and then regression with loss of hand skills and spoken language, gait problems, and hand stereotypies [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. After regression, a \u0026ldquo;Pseudostationary\u0026rdquo; stage occurs that has been characterized by no further skill loss and potential skill regain [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Eventually, a \u0026ldquo;Late Motor Decline\u0026rdquo; stage occurs, characterized by muscular rigidity, declining gross motor ability, and onset of Parkinsonian features [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAlthough previous work has described aspects of the gain and loss of developmental skills (also referred to as \u0026ldquo;developmental milestones\u0026rdquo;) [\u003cspan additionalcitationids=\"CR13 CR14\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], data on the frequency and timing of skill gain and loss remains incomplete, and evaluation of skill regain is minimally characterized. The need for this information is driven by the demonstration that restoration of MeCP2 function, even after symptom onset, can reverse phenotypic problems in RTT mouse models [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. This provided the foundation for disease modifying therapy development, such as gene therapy clinical trials for RTT [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Transformative therapies for RTT should change the course of the disease by enabling the acquisition of new skills, restoring lost skills, or preventing skill loss. Therefore, it is critical to understand the expected trajectory of skill gain, loss, and regain in RTT to objectively evaluate the therapeutic impact of novel therapies compared to historical data.\u003c/p\u003e\u003cp\u003eFrom 2006\u0026ndash;2021, the multi-site US Rett syndrome and Rett-related disorders Natural History Study (RNHS) longitudinally evaluated a large number of people with RTT [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], providing information on the clinical features and disease progression of RTT [\u003cspan additionalcitationids=\"CR21 CR22 CR23 CR24 CR25 CR26 CR27\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e], identifying and evaluating putative biomarkers [\u003cspan additionalcitationids=\"CR30 CR31 CR32\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e], developing outcome measures [\u003cspan additionalcitationids=\"CR35 CR36 CR37 CR38 CR39\" citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e], and establishing a clinical research network to enable the development of the first FDA-approved treatment for RTT [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. The RNHS captured information on developmental skill gain, loss, and regain from people with RTT, and analysis of early data from the RNHS provided information about developmental skill gain and loss [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. However, this previous work was limited by a smaller sample size and data on fewer skills compared with information available after the RNHS completion. Further, the previous work focused on skill gain or loss and did not evaluate skill regain or the incidence of skill gain or regain within a clinical trial timeframe.\u003c/p\u003e\u003cp\u003eTo address this need, we characterized the frequency and timing of skill gain, loss, and regain in females with Classic RTT and a pathogenic variant in \u003cem\u003eMECP2\u003c/em\u003e using the extensive RNHS dataset. We evaluated the time from gain to loss and the time from loss to regain to understand the temporal relationship between events. Further, we characterized the fraction of participants who gained a skill beyond either 4 or 6 years old, regained a skill beyond 6 years old or more than 2 years after loss, as well as determining the one-year incidence of gaining or regaining a skill. This work provides detailed information on the trajectory of developmental skill gain, loss, and regain in RTT to facilitate earlier diagnosis, guide clinical management, and establish foundational information relevant to the evaluation of disease modifying therapies for RTT.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eParticipants\u003c/h2\u003e\u003cp\u003eParticipants were enrolled in the Rett syndrome and RTT-related Disorders Natural History Study (RNHS, NCT00299312, NCT02738281), a longitudinal study incorporating caregiver-provided historical and clinically observed information spanning from 2006 to 2021 [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Participants were included in the RNHS if they had a clinical diagnosis of RTT based on the clinical consensus criteria [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], had a pathogenic variant in \u003cem\u003eMECP2\u003c/em\u003e but did not meet RTT clinical diagnostic criteria, or had a diagnosis of a RTT-related disorder (\u003cem\u003eMECP2\u003c/em\u003e duplication syndrome, \u003cem\u003eCDKL5\u003c/em\u003e deficiency disorder, or \u003cem\u003eFOXG1\u003c/em\u003e syndrome). Participants enrolled provided genetic testing results, although not all enrolled participants had an identified pathogenic genetic variant. All participants or their legally authorized representatives provided informed consent before participation in the RNHS. The RNHS was conducted in accordance with the Declaration of Helsinki, and approved by the University of Alabama, Birmingham Institutional Review Board. A Certificate of Confidentiality was provided by the National Institute of Child Health and Development (NICHD). Overall, 1826 individuals participated in the RNHS with an average of ~\u0026thinsp;5 visits per individual.\u003c/p\u003e\u003cp\u003eFor this study, we restricted analyses to female participants diagnosed with Classic RTT with a pathogenic variant in \u003cem\u003eMECP2\u003c/em\u003e who had some data collected on developmental milestone skill gain, loss, or regain (N\u0026thinsp;=\u0026thinsp;1228). The mean age of first visit for this cohort was 11.7 years (Standard Error of the Mean [SEM]\u0026thinsp;=\u0026thinsp;0.28 years), with a median age of enrollment of 8.2 years (Interquartile Range [IQR]\u0026thinsp;=\u0026thinsp;4.2\u0026ndash;16.4 years). The median number of study visits was 5 (range: 1\u0026ndash;17; IQR: 2\u0026ndash;8). The majority (71.3%) were white and not Hispanic (see \u003cb\u003eAdditional file 1: Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e Demographic Information\u003c/b\u003e for complete demographic information). \u003cb\u003eAdditional file 2: Table \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e MECP2 Mutation Frequency\u003c/b\u003e displays the breakdown of the frequency of common \u003cem\u003eMECP2\u003c/em\u003e point mutations and other mutation groups in the analysis cohort. For \u003cem\u003eMECP2\u003c/em\u003e mutation groups, we grouped rare point mutations affecting the same amino acid codon as common recurrent point mutations into the common point mutations. Specifically, participants with R106Q variants were grouped with R106W; those with R133P or R134C variants were grouped with R133C; participants with T158A or T158P were grouped with T158M, and participants with R306H or R306L were grouped with R306C. The Early Truncations group included all nonsense of frameshift variants before position R270, including splice site variants, but excluding the common recurrent nonsense point variants (R168X, R255X, R270X). The C-terminal Truncations group included all frameshift or nonsense variants after position R270, excluding the common recurrent nonsense point mutation R294X. Other point mutations encompass all other missense variants aside from the common recurrent variants (R106W, R133C, T158M, R306C). This approach to grouping pathogenic genetic variants is consistent with previous work [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eVisit Schedule and Assessments\u003c/h3\u003e\n\u003cp\u003eParticipants were assessed in a structured in-person clinical research visit (lasting\u0026thinsp;~\u0026thinsp;1\u0026ndash;2 hours), which occurred longitudinally at pre-defined intervals based on age of enrollment, ranging from twice per year to every other year [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. In-person evaluations utilizing structured research forms including caregiver completed history and assessment forms and questionnaires, clinical histories, structured clinical exams, and clinician-completed rating scales. Information on the gain, loss, and regain of developmental skills was captured through a detailed, direct interview with caregivers. Caregivers were provided a developmental skill history questionnaire prior to the baseline visit and asked to provide information on whether a specified skill was gained, lost, or regained and the age of gain, loss, or regain (or indicate age of skill event being unknown). Caregivers were instructed to review and refer to aids to improve recall such as baby books and pictures, and review of prior medical evaluations by primary care physicians and any subspecialists. During the in-person baseline visit, the developmental skill history questionnaire was reviewed by the clinical investigator with the caregiver to discuss and confirm the answers provided by the caregiver, as well as raise questions about the caregiver\u0026rsquo;s responses with regards to the current ability of the participant (\u003cem\u003ee.g.\u003c/em\u003e if caregiver stated that the participant had gained but not lost a skill, but the participant was not able to perform the skill during the clinical evaluation or by parent report, the investigator would ask for clarification of the developmental history report provided that indicated that the skill was not lost). At all subsequent visits, the developmental history log was reviewed with the caregiver to assess whether any changes occurred since the previous study visit with regards to skills being gained, lost, or regained and updates to the form made to reflect these changes.\u003c/p\u003e\u003cp\u003eFrom 2006\u0026ndash;2014, the developmental skill history questionnaire queried 31 developmental skills (NCT00299312, RNHS protocol 5201). In 2015, upon initiation of the third funding cycle, the data capture forms underwent a major revision including modification of the developmental skill history questionnaire (NCT02738281, RNHS protocol 5211), which added a number of new developmental skills to expand the range and detail of developmental milestones assessed and dropped three skills captured in the previous protocol (Roll Back to Front, Pedal Tricycle, and Stopped Being Visually Attentive) based on analysis showing either floor or ceiling effects for these three skills. The new developmental skill history questionnaire included a total of 51 developmental skills, with 28 mapping to skills captured in 5201 and the addition of 23 additional skills. The names of the skills in both protocols, the mapping of the skills between the two protocols, and the names used for the skills in this paper are provided in \u003cb\u003eAdditional file 3: Table \u003cspan refid=\"MOESM3\" class=\"InternalRef\"\u003eS3\u003c/span\u003e Developmental skill mapping between protocols 5201 and 5211\u003c/b\u003e. For this study, we analyzed the 51 skills assessed in protocol 5211 (2015\u0026ndash;2021) and merged the information from the two protocols as shown in \u003cb\u003eAdditional file 3: Table \u003cspan refid=\"MOESM3\" class=\"InternalRef\"\u003eS3\u003c/span\u003e Developmental skill mapping between protocols 5201 and 5211\u003c/b\u003e. For participants meeting the inclusion criteria for these analyses defined above (N\u0026thinsp;=\u0026thinsp;1228), 586 participated solely in 5201, 307 participated only in 5211, and 335 participated in both 5201 and 5211. For participants evaluated in both 5201 and 5211, initial age of skill events provided were used in cases when there were discrepancies between dates identified between data collected in the two protocols; however, updated information collected during 5211 reflecting changes in skill event occurrence from 5201 were used to reflect changes in skill gain, loss, or regain over time. Total Ns (Tables\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e) reflect total number of participants from 5201 and or 5211 with information available on skill gain, loss, or regain post data processing and cleaning described below. The calculation of the mean and median age of skill gain, loss, or regain was based only data for which a specific age of event was obtained (excluding those participants with an \"age unknown\" indicator), thus the total number of participants included in these calculations are lower than the total number with data indicating whether the skill event occurred or did not occur.\u003c/p\u003e\n\u003ch3\u003eData processing and cleaning prior to analyses\u003c/h3\u003e\n\u003cp\u003ePrior to analysis, the raw data went through a series of processing and data cleaning steps. Prior to data cleaning, data fields coded as \u0026ldquo;Yes\u0026rdquo; or \u0026ldquo;No\u0026rdquo; were recoded as \u0026ldquo;1\u0026rdquo; or \u0026ldquo;0\u0026rdquo;. The full description of the cleaning process criteria is provided in \u003cb\u003eAdditional file 4: Supplemental Methods\u003c/b\u003e, including the number of changes (n) made according to each criterion. Overall, this process resulted in changes to 26,170 data cells, which represents changes to 4.64% of all data cells. The changes fell into the following broad categories:\u003c/p\u003e\u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eMost changes were to skill event occurrence indicators (n\u0026thinsp;=\u0026thinsp;23,575; 4.22%), with the vast majority of these removing subsequent skill event indicator of \u0026ldquo;No\u0026rdquo; when preceding skill event did not occur (n\u0026thinsp;=\u0026thinsp;22,537, 4.0%). The remaining changes to skill event occurrence indicators (n\u0026thinsp;=\u0026thinsp;1,221; 0.22%) added missing skill event indicators to subsequent skill events when preceding skill event occurred, correcting preceding skill event indicators when subsequent skill occurred, or adding missing skill event occurrence indicator when age of skill event was provided or age of skill event was indicated as \u0026ldquo;unknown\u0026rdquo;.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eThe next largest group of changes were corrections to age of skill event unknown indicators to remove the age of skill event unknown indicator if the age of skill event was provided, or add skill event unknown indicator when event occurred but the age of skill event was not entered and the age of skill event unknown indicator was blank (n\u0026thinsp;=\u0026thinsp;1,205, 0.2%)\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eCorrecting logical age inconsistencies (\u003cem\u003ee.g.\u003c/em\u003e the age of skill event entered was beyond the age of last visit or before the preceding skill event age) was the next largest group of changes (n\u0026thinsp;=\u0026thinsp;736, 0.13%)\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eIdentifying entries for the age of skill gain that was at an unrealistically young age of gain and removing age of gain and adding age of gain unknown indicator was the next largest group of changes (n\u0026thinsp;=\u0026thinsp;590, 0.1%)\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eFinally, the smallest group of changes were based on review of source data (n\u0026thinsp;=\u0026thinsp;64, 0.01%)\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e\u003cp\u003eAfter cleaning, all ages were converted from \u0026ldquo;months\u0026rdquo; to \u0026ldquo;years\u0026rdquo; (with 1 decimal point) by dividing months by 12. For all skill events that were identified as not having occurred (and not blank), the age of last visit (in years) was inserted into the age of event field as \u0026ldquo;censored age\u0026rdquo; data for subsequent survival analysis.\u003c/p\u003e\n\u003ch3\u003eStatistical Analyses and Data Visualization\u003c/h3\u003e\n\u003cp\u003eAll data was stored and processed in Excel v16 (Microsoft). The presentation of the data for this study is descriptive; no hypothesis tests were performed. SPSS v29.0.2.0 (IBM, Armon, NY, USA) was used to calculate proportions, mean values with standard error of the mean (SEM), median values, and Kaplan-Meyer (cumulative incidence) survival tables. The overall rate of gain, loss, or regain for each skill for all cases with information on the status of the event (including those without information on the age of the event) was calculated as the proportion (presented as percentage) of individuals in which the event occurred over all individuals with information for that skill event. Because the denominator varies across skill events, the raw number for the numerator (individuals in which the skill event occurred) and the denominator is presented. Confidence Intervals (95%) for skill event proportions were calculated using the BINOMIAL function in SPSS using Likelihood (normal approximation) unless the number of individuals in which an event occurred [n(p)] or did not occur [n(1-p)] was less than 5, or if the proportion of occurrence (p) or non-occurrence (1-p) was less than 0.10, in which the Clopper-Pearson exact method was used. Mean and median age of event was calculated using only individuals with available information as no imputation was performed. Median skill event age and age range (5–95%) was calculated using the ROUND function in SPSS. Cumulative incidence tables were calculated using Kaplan-Meyer survival analysis, with censoring if the skill event did not occur. The age of last visit was used for the censored age for skill gain, loss, or regain. For time from gain to loss or time from loss to regain, the censored age was the age of last visit minus the age of the preceding skill event. The cumulative incidence tables were used to calculate the percent of individuals who gained a skill beyond 4 years or 6 years of age, regained a skill beyond 6 years of age, or regained a skill more than 2 years after losing that skill. Additionally, we used these cumulative incidence tables to determine the percentage of individuals who did not gain a skill by the age the US Centers for Disease Control (CDC) indicates that most children (75% based on normative data) are expected to achieve that skill [44]. This calculation was only done for those skills for which CDC normative age recommendations for surveillance are available (41 of the 51 skills assessed in this study). Graphical representation of cumulative incidence curves (survival or 1-survival curves) was generated using R v4.5 (www.r-project.org), with Powerpoint v16.1 (Microsoft) used to create merged figures of representative cumulative incidence curves.\u003c/p\u003e\n\u003cp\u003eThe incidence of either gaining or regaining a skill during a one-year interval was calculated for one-year bins from 0–20 years of age. For the analysis of one-year interval incidence, information of gain or regain of skills beyond 20 years of age was not included. To determine the one-year incidence of gain or regain for each skill, the number of individuals who gained or regained that skill within the one-year interval was divided by the total number of individuals eligible to either gain or regain the skill during the specified interval. The detailed logic used to determine skill gain or regain and eligibility in each interval is provided in the \u003cstrong\u003eAdditional file 4: Supplemental Methods\u003c/strong\u003e. For each individual, the total number of skills gained or regained in each one-year interval was calculated, and the percentage of individuals who gained at least 1 of 51 or 1 of the 38 skills selected (described in the results section) was determined by dividing by the total number of participants eligible to gain or regain a skill in that interval.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003ch2\u003eDevelopmental Skill Gain\u003c/h2\u003e\n \u003cp\u003eDelayed or absent acquisition of developmental skills is a well-recognized feature in RTT [\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e]. The percentage of participants in this study who gained specific developmental skills ranged from 99.5% for Social Smile to 2.4% for Shared Stories (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Across developmental skill domains (gross motor, fine motor, receptive language, expressive language, social/adaptive skills), the frequency of skill gain was highest for lower level and earlier acquired skills than for more advanced skills. For example, within the gross motor skill domain, nearly 100% of participants gained early skills such as lifting head, rolling from tummy, and sitting with or without support, but only\u0026thinsp;~\u0026thinsp;60% gained the ability to walk independently (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Similarly, within expressive language, nearly all participants gained early skills such as Cooing and Babbling, but less than 25% gained Spoken Phrases. Out of the 51 skills characterized, 21 individual skills were gained by over 80% of all participants and only 2 skills were gained by less than 20% of all participants (Down Stairs Without Help and Shared Stories).\u003c/p\u003e\n \u003cp\u003eIn the participants that age of skill gain was known, the mean age of skill gain (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e) ranged from 0.2 years (Like Being Held) to 6.9 years (Shared Stories), and the median ages of skill gain ranged from 0.1 years (Like Being Held) to 3 years (Point to 1 Color). Examples of cumulative incidence curves (Kaplan-Meyer 1-Survival curves) for the gain of representative developmental skills are shown in Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e, with curves for all developmental skills provided in \u003cstrong\u003eAdditional file 5: Figure \u003cspan class=\"InternalRef\"\u003eS1\u003c/span\u003e\u003c/strong\u003e. The median age of skill gain was one year or younger for 33 of the 51 skills (65%), and two years or younger for 50 skills (98%) (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). For 26 of the 51 developmental skills (51%), 95% of participants who gained that skill did so by 2 years old (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). By 4 years of age, this increased to 73% of the skills (37 of 51 skills), and by 6 years old it increased to 92% of the skills (47 of 51 skills). For each developmental skill, we calculated the percentage of participants who gained the skill after age 4 or 6 years of age (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). The percentage of participants who gained a specific skill after 4 years of age was less than 5% for all skills except Point to 1 Color. The percentage of participants who gained a specific skill after 6 years of age was less than 2.5% for 50 of the 51 skills, with the majority (35 of 51) of the skills being gained by 1% or less of participants who gained the skill. These data demonstrate that acquisition of the skills evaluated in this study generally occurs early in life in people with RTT, with the majority (95%) of people who gain a specific skill doing so before 4 years of life, and 97.5\u0026ndash;99% who gain a specific skill doing so before 6 years of life.\u003c/p\u003e\n \u003cp\u003eThe US Centers for Disease Control (CDC) has developed normative guidelines for developmental surveillance based on the age that most (\u0026thinsp;\u0026gt;\u0026thinsp;=\u0026thinsp;75%) of children should attain specific developmental skills to help with early identification of children with developmental delays or disabilities [\u003cspan class=\"CitationRef\"\u003e44\u003c/span\u003e] (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.cdc.gov/act-early/index.html\u003c/span\u003e\u003c/span\u003e). Of the 51 developmental skills evaluated in this study, CDC age-specific surveillance recommendations are available for 41 skills. We characterized the percentage of participants in this study who had not yet gained a specific skill by these CDC recommendations (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). The percentage of participants who did not gain a skill by the CDC guidelines ranged from 14.6% (Sit Without Support) to 99.5% (Shared Stories). Notably, in 26 of the 41 (63.4%) skills with CDC recommended age of gain, the majority (\u0026gt;\u0026thinsp;50%) of study participants did not gain the skill by the CDC threshold age. For advanced skills such as Shared Stories, the age that most children are expected to gain the skill is beyond the typical age of regression in RTT (~\u0026thinsp;18 months [\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e45\u003c/span\u003e]). However, it is notable that a significant percentage of participants fail to acquire lower-level skills that are expected to be gained before 6 months of life, such as Lift Head (59.3%), Hold Bottle (84.8%), Social Smile (45.9%), and Eyes Fix and Follow (70.2%). Furthermore, a significant percentage also failed to gain major milestones that are expected to be gained by 18 months of life (1.5 years) such as Pull to Stand (62.1%), Walk Independently (66.8%), Pincer Grasp (41.6%), Words with Meaning (45.8%), and Point for Wants (84.2%). As the average age of diagnosis of RTT is 2.7 years [\u003cspan class=\"CitationRef\"\u003e46\u003c/span\u003e], these notable early departures from expected age of gain of developmental skills should raise concerns for caregivers and primary care providers.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003e\u003cstrong\u003eDevelopmental Skill Gain\u003c/strong\u003e.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSkill Gain\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eAll Cases\u003c/span\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eAge Gain (yr)\u003c/span\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e% Not Gained by\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e% Gain Beyond Age\u003c/span\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal N\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e% Gain\u003c/p\u003e\n \u003cp\u003e(95% CI, N)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003cp\u003e(SEM, N)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eMedian\u003c/p\u003e\n \u003cp\u003e(5%, 95%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eCDC (yr)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;4yo\u003c/p\u003e\n \u003cp\u003e( N )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;6yo\u003c/p\u003e\n \u003cp\u003e( N )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGross Motor\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLift Head\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e636\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e98.1 (96.7\u0026ndash;99.0, 624)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.3 (0.02, 315)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.3 (0.1, 0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e59.3 (0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.3 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRoll From Tummy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1224\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e96.0 (94.7\u0026ndash;97.0, 1175)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.5 (0.01, 983)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.4 (0.2, 0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e25.9 (0.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSit With Support\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e637\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e98.6 (97.3\u0026ndash;99.4, 628)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.6 (0.02, 494)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.5 (0.3, 0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e36.8 (0.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.2 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSit Without Support\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1227\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e97.1 (96.0-97.9, 1191)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.7 (0.01, 1050)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.6 (0.3, 1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e14.6 (0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.4 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.3 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCome To Sit\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1227\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e83.0 (80.8\u0026ndash;85.0, 1018)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.9 (0.02, 843)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.8 (0.4, 1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e45.1 (0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.3 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCrawl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1225\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e70.9 (68.3\u0026ndash;73.4, 868)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (0.02, 785)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.9 (0.5, 1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cem\u003eN/A\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.3 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStand With Support\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e633\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e85.6 (82.7\u0026ndash;88.2, 542)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.1 (0.03, 371)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.0 (0.7, 2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cem\u003eN/A\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.8 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePull To Stand\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1228\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e67.7 (65-70.2, 831)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.1 (0.02, 724)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.0 (0.6, 2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e62.1 (1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWalk With Support\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1226\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e79.0 (76.7\u0026ndash;81.3, 969)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.4 (0.03, 850)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.1 (0.8, 2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e66.6 (1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.4 (12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.3 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStand Independently\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e635\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e64.7 (61-68.4, 411)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.6 (0.1, 261)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.4 (0.8, 3.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cem\u003eN/A\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.7 (7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.5 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWalk Independently\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1227\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e59.3 (56.5\u0026ndash;62.0, 727)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.7 (0.04, 695)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.5 (1.0, 3.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e66.8 (1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.8 (17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.0 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRan 10 Feet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e638\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e29.5 (26.0-33.1, 188)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.9 (0.1, 99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.6 (1.1, 3.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e86.5 (2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.5 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.5 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUp Stairs With Help\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e636\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e53.9 (50.0-57.8, 343)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.4 (0.1, 194)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e2.0 (1.0, 5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cem\u003eN/A\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.2 (17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.4 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUp Stairs WO Help\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1226\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e25.9 (23.5\u0026ndash;28.4, 318)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.3 (0.1, 235)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e2.0 (1.0, 5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e87 (2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.9 (18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.5 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDown Stairs With Help\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e637\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e44.0 (40.1\u0026ndash;47.8, 280)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.7 (0.1, 147)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e2.0 (1.0, 6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cem\u003eN/A\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.1 (16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.8 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDown Stairs WO Help\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1227\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e19.6 (17.5\u0026ndash;21.9, 241)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.7 (0.2, 173)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e2.0 (1.0, 6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cem\u003eN/A\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.1 (17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.3 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eFine Motor\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHold Bottle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1226\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e88.9 (87.1\u0026ndash;90.6, 1090)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.7 (0.01, 889)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.6 (0.3, 1.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e84.8 (0.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReach For Toy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1226\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e97.6 (96.7\u0026ndash;98.4, 1197)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.6 (0.02, 934)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.4 (0.2, 1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e32.2 (0.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.4 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.3 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRaking Grasp\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e636\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e89.8 (87.3\u0026ndash;92.0, 571)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.8 (0.1, 278)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.6 (0.3, 2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e37 (0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.2 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.9 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTransfer Objects\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1226\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e76.8 (74.4\u0026ndash;79.1, 942)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.8 (0.03, 653)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.7 (0.3, 2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e50.5 (0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.3 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.2 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePincer Grasp\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1226\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e76.8 (74.3\u0026ndash;79.1, 941)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (0.03, 708)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.8 (0.5, 2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e41.6 (1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.9 (7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.4 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFinger Feeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1227\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e92.1 (90.4\u0026ndash;93.5, 1130)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.9 (0.02, 915)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.8 (0.5, 1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e16.7 (1.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.4 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.2 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTurn Pages in Book\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e636\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e56.0 (52.1\u0026ndash;59.8, 356)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.2 (0.1, 196)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.0 (0.6, 2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e60.3 (2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.5 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.3 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eExpressive\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSocial Smile\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1225\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e99.5 (98.9\u0026ndash;99.8, 1219)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.3 (0.01, 991)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.2 (0.1, 0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e45.9 (0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCooing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1225\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e94.1 (92.7\u0026ndash;95.4, 1153)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.3 (0.01, 861)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.3 (0.1, 0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e24.4 (0.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBabbling\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1224\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e95.3 (94.0-96.5, 1167)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.7 (0.02, 898)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.5 (0.3, 1.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e22.2 (0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.4 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWords With Meaning\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1226\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e76.7 (74.3\u0026ndash;79.0, 940)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.1 (0.02, 782)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.0 (0.5, 2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e45.8 (1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.6 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSpoken Phrases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1223\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e23.5 (21.1\u0026ndash;25.9, 287)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.0 (0.1, 196)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.5 (1.0, 4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e86.9 (2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.0 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.4 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWave Bye\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1224\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e58.5 (55.7\u0026ndash;61.2, 716)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.1 (0.1, 551)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.8 (0.5, 2.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e58.9 (1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.9 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePoint for Wants\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1222\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e30.5 (28.0-33.1, 373)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.7 (0.1, 265)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.0 (0.5, 4.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e84.2 (1.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.2 (14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.6 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eShared Stories\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e636\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e2.4 (1.4\u0026ndash;3.7, 15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.9 (3.1, 6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e2.0 (1.3, 21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e99.5 (4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.9 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eReceptive\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eQuiet To Voice\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1223\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e90.0 (88.2\u0026ndash;91.6, 1101)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.4 (0.03, 724)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.2 (0.0, 1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e49.4 (0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.2 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.6 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRespond To Sounds\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e637\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e97.5 (96.0-98.6, 621)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.3 (0.03, 311)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.2 (0.0, 0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e39.6 (0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.3 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePlay Peek-A-Boo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e633\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e62.6 (58.7\u0026ndash;66.3, 396)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.7 (0.04, 181)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.6 (0.3, 1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e66.5 (0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRespond To Words\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e636\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e91.7 (89.4\u0026ndash;93.6, 583)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.9 (0.1, 254)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.7 (0.3, 2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cem\u003eN/A\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.3 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.3 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRespond To Own Name\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e637\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e96.2 (94.6\u0026ndash;97.5, 613)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (0.1, 257)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.7 (0.3, 3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e40.2 (0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.4 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.6 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eInhibit To No\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1225\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e72.4 (69.9\u0026ndash;74.9, 887)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.4 (0.1, 558)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.0 (0.5, 3.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e60.3 (1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.9 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.3 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCommands With Gesture\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1220\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e59.6 (56.8\u0026ndash;62.3, 727)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.8 (0.1, 460)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.1 (0.5, 5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e71.7 (1.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.5 (32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e2.2 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCommands WO Gesture\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1225\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e48.5 (45.7\u0026ndash;51.3, 594)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.0 (0.1, 366)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.3 (0.7, 6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e77.7 (1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.6 (31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e2.4 (12)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIdentify Body Parts\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e634\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e41.8 (38.0-45.7, 265)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.4 (0.2, 120)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.5 (0.8, 6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e82.4 (2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.2 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e2.0 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePoint to 1 Color\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e635\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e46.9 (43.1\u0026ndash;50.8, 298)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.9 (0.3, 134)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e3.0 (1.0, 10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e88.1 (2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.3 (43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e7.3 (22)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSocial/Adaptive\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLike Being Held\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1223\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e96.0 (94.7\u0026ndash;97.0, 1174)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.2 (0.02, 880)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.1 (0.0, 0.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cem\u003eN/A\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.2 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAttention to Sounds\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e634\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e89.4 (86.9\u0026ndash;91.7, 567)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.5 (0.1, 240)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.3 (0.0, 1.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e68.1 (0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.7 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.7 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEyes Fix and Follow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1221\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e95.1 (93.8\u0026ndash;96.2, 1161)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.5 (0.04, 749)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.3 (0.1, 1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e70.2 (0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.4 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.1 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePlay Pat-A-Cake\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e633\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e28.1 (24.7\u0026ndash;31.7, 178)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.8 (0.05, 83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.8 (0.5, 1.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e86.8 (1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDesire Social Attention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e632\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e84.8 (81.9\u0026ndash;87.5, 536)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.8 (0.1, 232)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.3 (0.0, 3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cem\u003eN/A\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.9 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.9 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eImitate Peers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e629\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e21.3 (18.2\u0026ndash;24.6, 134)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.2 (0.4, 58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.1 (0.7, 6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e94.2 (1.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.6 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.0 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBeen Independent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e630\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e35.6 (31.9\u0026ndash;39.3, 224)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.4 (0.3, 96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.3 (0.8, 8.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cem\u003eN/A\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.8 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e2.1 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDrinks WO Help\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e636\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e61.5 (57.7\u0026ndash;65.2, 391)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.2 (0.1, 199)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.0 (0.5, 2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e61.7 (1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.4 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.4 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUses Utensils With Help\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e636\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e67.5 (63.7\u0026ndash;71.0, 429)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.8 (0.1, 215)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.2 (0.7, 5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e64.5 (1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.6 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.3 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUses Utensils WO Help\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e636\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e26.6 (23.2\u0026ndash;30.1, 169)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.3 (0.3, 76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.3 (0.8, 8.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e88.4 (2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.3 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.9 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eTable \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eLegend\u003c/span\u003e: The first column in the table displays the total number (N) for all cases with information available whether the specific developmental skill was gained or not. The second column shows the percentage (%), 95% Confidence Interval (CI) and number of individuals (N) who gained each skill. * Indicates where the Clopper-Pearson exact method was used to calculate the CI. The third and fourth columns present the age of skill gain in years (yr) and the standard error of the mean (SEM) for cases with a known age of gain (N), and the median age of skill gain with 5\u0026ndash;95% intervals yrs). The fifth column shows the percent of individuals who did not gain a specific skill by the CDC defined age threshold (displayed in parentheses). N/A indicates that no normative CDC threshold is available for that particular skill. Finally, the percentage of individuals who gain the skill beyond either 4 years old (yo) or 6 years old (yo) is displayed in the last two columns, including the total number (N) who gained the skill beyond the specific age cutoff. Skill domains are demarked on left side. Expressive Communication is labeled \u0026ldquo;Expressive\u0026rdquo; and Receptive Communication is labeled \u0026ldquo;Receptive\u0026rdquo;.\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003eDevelopmental skill loss\u003c/h3\u003e\n\u003cp\u003eRegression, or loss of previously acquired developmental skills, is a defining characteristic of RTT [\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e]. Therefore, we calculated the percentage of participants who lost specific skills previously gained, as well as the mean and median age of skill loss (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). The percentage of participants who lost previously gained skills ranged from 6.6% (Lift Head) to 88.6% (Words with Meaning). The high frequency of loss of Fine Motor and Expressive Language skills is consistent with regression in these domains being a \u003cem\u003econditio sine qua non\u003c/em\u003e of RTT [\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e]. However, Gross Motor, Receptive Language, and Social/Adaptive skills are also lost in a significant fraction of people with RTT.\u003c/p\u003e\n\u003cp\u003eThe mean age of skill loss ranged from 1.6 years old (Cooing, Respond to Sounds) to 8.2 years old (Down Stairs With Help), and the median age of loss ranged from 1.3 years old (Cooing) to 7.3 years old (Down Stairs With Help). The median age of skill loss was 3 years old or less for 46 of the 51 developmental skills (90%), and in 31 developmental skills, 95% of participants lost skills by 6 years old. Cumulative incidence curves (Kaplan-Meyer Survival curves) of loss of representative developmental skills are shown in Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e (Panels A1, B1, C1, D1, E1), with loss curves for all developmental skills provided in Additional file 6: \u003cstrong\u003eFigure \u003cspan class=\"InternalRef\"\u003eS2\u003c/span\u003e\u003c/strong\u003e. Notably, while most skill domains show a relatively tight window of loss across all participants, the loss of Gross Motor domain skills such as Stand Independently or Walk Independently occurs more gradually and over a longer time period (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e and Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cstrong\u003eA1\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003eGiven the variation in the age of skill gain, we calculated the time from gain to loss for all developmental skills (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cstrong\u003e)\u003c/strong\u003e. The mean time from gain to loss ranged from 0.7 years (Point to 1 Color) to 6.6 years (Stand Independently), and the median time from gain to loss ranged from 0.5 years (Words With Meaning, Spoken Phrases) to 5.3 years (Stand Independently). Overall, the median time from gain to loss was less than 2 years for 44 of the 51 developmental skills (86.3%). Consistent with the analysis of the age of loss, the skills that had median time from gain to loss greater than 2 years were all within the gross motor domain such as Stand Independently (5.3 years), Walk Independently (4.0 years), or Down Stairs With Help (5.0 years). Figure \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e (Panels A2, B2, C2, D2, E2) shows cumulative incidence curves for the time from gain to loss for representative developmental skills, with gain to loss cumulative incidence curves for all developmental skills provided in\u0026nbsp;\u003cstrong\u003eAdditional file: Figure \u003cspan class=\"InternalRef\"\u003eS3\u003c/span\u003e\u003c/strong\u003e.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003e\u003cstrong\u003eDevelopmental Skill Loss\u003c/strong\u003e.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSkill Loss\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eAll Cases\u003c/span\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eAge Loss (yr)\u003c/span\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eTime Gain to Loss (yr)\u003c/span\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal N\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e% Loss\u003c/p\u003e\n \u003cp\u003e(95% CI, N)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003cp\u003e(SEM, N)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian\u003c/p\u003e\n \u003cp\u003e(5%, 95%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003cp\u003e(SEM, N)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian\u003c/p\u003e\n \u003cp\u003e(5%, 95%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGross Motor\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLift Head\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e624\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.6 (4.8\u0026ndash;8.8, 41)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e3.9 (1.2, 18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.6 (0.5, 14.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.4 (1.4, 15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.2 (0.2, 13.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRoll From Tummy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1175\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34.0 (31.4\u0026ndash;36.8, 400)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e3.6 (0.3, 281)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.0 (0.7, 12.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.9 (0.3, 255)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.4 (0.1, 10.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSit With Support\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e628\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.2 (10.7\u0026ndash;16.0, 83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e5.2 (0.6, 61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.0 (1.0, 12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.6 (0.7, 53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.4 (0.2, 11.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSit Without Support\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1191\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19.4 (17.2\u0026ndash;21.7, 231)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e5.1 (0.4, 179)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.0 (0.9, 13.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.4 (0.4, 170)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.3 (0.2, 12.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCome To Sit\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.8 (24.2\u0026ndash;29.6, 273)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e4.8 (0.3, 201)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.0 (1.0, 13.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.6 (0.3, 181)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.7 (0.2, 12.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCrawl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e868\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25.3 (22.5\u0026ndash;28.3, 220)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e3.8 (0.3, 149)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.0 (1.2, 12.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.8 (0.3, 140)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.2 (0.2, 11.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStand With Support\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e542\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28.4 (24.7\u0026ndash;32.3, 154)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e5.3 (0.6, 96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.2 (1.0, 17.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.3 (0.7, 80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.2 (0.2, 18.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePull To Stand\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e831\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42.1 (38.8\u0026ndash;45.5, 350)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e4.1 (0.3, 266)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.5 (1.3, 12.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.9 (0.3, 253)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (0.1, 11.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWalk With Support\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e969\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25.9 (23.2\u0026ndash;28.7, 251)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e4.8 (0.3, 188)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.0 (1.2, 13.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.5 (0.4, 172)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.3 (0.1, 12.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStand Independently\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e411\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29.0 (24.7\u0026ndash;33.5, 119)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e7.8 (0.8, 74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.5 (1.0, 22.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.6 (0.9, 58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.3 (0.1, 22.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWalk Independently\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e727\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28.3 (25.1\u0026ndash;31.7, 206)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e7.8 (0.5, 177)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.0 (1.3, 22.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.0 (0.5, 164)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.0 (0.0, 20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRan 10 Feet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e188\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42.6 (35.6\u0026ndash;49.7, 80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e6.1 (0.8, 48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.0 (1.0, 16.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.0 (1.1, 32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.3 (0.3, 14.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUp Stairs With Help\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e343\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30.3 (25.6\u0026ndash;35.3, 104)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e7.3 (0.8, 55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.5 (1.4, 15.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.4 (0.8, 43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.0 (0.3, 12.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUp Stairs Without Help\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e318\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41.5 (36.2\u0026ndash;47.0, 132)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e4.7 (0.4, 96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.0 (1.4, 15.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.8 (0.4, 81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.4 (0.2, 10.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDown Stairs With Help\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e280\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31.1 (25.8\u0026ndash;36.6, 87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e8.2 (0.9, 49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.3 (1.5, 22.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.4 (1, 35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.0 (0.2, 17.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDown Stairs WO Help\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e241\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e44.0 (37.8\u0026ndash;50.3, 106)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e4.8 (0.5, 77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.0 (1.3, 14.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.1 (0.5, 65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (0.1, 12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eFine Motor\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHold Bottle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1090\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60.5 (57.5\u0026ndash;63.3, 659)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e2.5 (0.1, 557)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.0 (1.0, 6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.8 (0.1, 497)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.2 (0.2, 5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReach For Toy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1197\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e56.8 (54.0-59.6, 680)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e2.2 (0.1, 569)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.7 (1.0, 4.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.6 (0.1, 488)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.2 (0.4, 3.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRaking Grasp\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e571\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e58.0 (53.9\u0026ndash;62.0, 331)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e2.8 (0.2, 219)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.0 (1.0, 7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.2 (0.3, 148)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.3 (0.3, 8.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTransfer Objects\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e942\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71.0 (68.1\u0026ndash;73.9, 669)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e2.2 (0.1, 526)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.8 (1.0, 4.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.4 (0.1, 428)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (0.3, 3.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePincer Grasp\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e941\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76.2 (73.4\u0026ndash;78.8, 717)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e2.3 (0.1, 602)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.0 (1.0, 5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.3 (0.1, 511)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (0.2, 3.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFinger Feeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1130\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e63.7 (60.9\u0026ndash;66.5, 720)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e2.5 (0.1, 624)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.0 (1.0, 5.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.6 (0.1, 540)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (0.2, 4.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTurn Pages in Book\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e356\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e74.7 (70.0\u0026ndash;79.0, 266)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e2.4 (0.1, 156)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.0 (1.2, 4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.3 (0.1, 113)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (0.3, 3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eExpressive\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSocial Smile\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1219\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18.2 (16.1\u0026ndash;20.4, 222)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e2.2 (0.2, 200)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5 (0.8, 4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.6 (0.1, 178)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.2 (0.3, 3.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCooing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1153\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40.2 (37.4\u0026ndash;43.1, 464)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.6 (0.1, 324)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.3 (0.5, 3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.2 (0.1, 288)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (0.2, 2.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBabbling\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1167\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55.4 (52.6\u0026ndash;58.3, 647)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.9 (0.1, 518)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5 (0.8, 4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.1 (0.1, 459)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.8 (0.2, 2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWords With Meaning\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e940\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e88.6 (86.5\u0026ndash;90.5, 833)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e2.0 (0.1, 755)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5 (0.9, 4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (0.1, 652)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.5 (0.1, 2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSpoken Phrases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e287\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e87.8 (83.7\u0026ndash;91.2, 252)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e2.5 (0.1, 202)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.0 (1.2, 5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (0.1, 144)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.5 (0.1, 2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWave Bye\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e716\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e87.8 (85.3\u0026ndash;90.1, 629)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e2.0 (0.1, 497)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5 (0.8, 4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (0.1, 422)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.7 (0.1, 2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePoint for Wants\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e373\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67.3 (62.4\u0026ndash;71.9, 251)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e2.3 (0.2, 184)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.9 (1.0, 4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.2 (0.2, 152)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.7 (0.2, 3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eShared Stories\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66.7 (38.4\u0026ndash;88.2, 10)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e2.7 (0.2, 6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.5 (2.0, 3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.1 (0.1, 3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (1.0, 1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eReceptive\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eQuiet To Voice\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1101\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23.7 (21.3\u0026ndash;26.3, 261)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.8 (0.1, 218)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5 (1.0, 3.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.4 (0.1, 171)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.2 (0.4, 2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRespond To Sounds\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e621\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15.8 (13.1\u0026ndash;18.8, 98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.6 (0.1, 78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5 (0.5, 3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.4 (0.1, 37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.2 (0.5, 2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePlay Peek-A-Boo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e396\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e57.8 (52.9\u0026ndash;62.6, 229)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.9 (0.1, 111)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5 (0.8, 3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.1 (0.1, 87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.9 (0.2, 2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRespond To Words\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e583\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19.6 (16.5\u0026ndash;22.9, 114)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.9 (0.1, 73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5 (1.0, 3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.1 (0.1, 55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.8 (0.3, 2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRespond To Own Name\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e613\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17.6 (14.7\u0026ndash;20.8, 108)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.7 (0.1, 75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5 (0.8, 3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.9 (0.1, 52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.8 (0.2, 2.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eInhibit To No\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e887\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.0 (23.2\u0026ndash;29.0, 231)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e2.0 (0.1, 161)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.6 (1.0, 4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.9 (0.1, 121)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.7 (0.2, 2.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCommands With Gesture\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e727\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e48.1 (44.5\u0026ndash;51.8, 350)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e2.2 (0.1, 230)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.9 (1.0, 5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.1 (0.1, 172)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.8 (0.2, 3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCommands WO Gesture\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e594\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45.8 (41.8\u0026ndash;49.8, 272)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e2.4 (0.1, 171)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.0 (1.1, 5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.2 (0.1, 128)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.7 (0.2, 3.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIdentify Body Parts\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e265\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e46.8 (40.8\u0026ndash;52.8, 124)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e2.5 (0.2, 68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.0 (1.1, 5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.1 (0.2, 55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.7 (0.2, 2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePoint to 1 Color\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e298\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20.5 (16.2\u0026ndash;25.3, 61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e2.2 (0.2, 28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.0 (0.3, 4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.7 (0.1, 21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.6 (0.2, 1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSocial /Adaptive\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLike Being Held\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1174\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19.5 (17.3\u0026ndash;21.8, 229)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.8 (0.1, 196)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5 (0.6, 3.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.6 (0.1, 160)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.4 (0.4, 2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAttention to Loud Sounds\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e567\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19.2 (16.1\u0026ndash;22.6, 109)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.8 (0.1, 80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5 (1.0, 3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.1 (0.1, 29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (0.2, 2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEyes Fix and Follow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1161\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29.7 (27.1\u0026ndash;32.4, 345)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.7 (0.1, 278)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5 (0.8, 3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.3 (0, 214)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.1 (0.4, 2.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePlay Pat-A-Cake\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e178\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e78.7 (72.2\u0026ndash;84.2, 140)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.9 (0.1, 71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5 (1.0, 3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (0.1, 53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.7 (0.2, 2.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDesire Social Attention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e536\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17.9 (14.8\u0026ndash;21.3, 96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e2.0 (0.2, 67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5 (0.8, 4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.3 (0.2, 37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.1 (0.4, 2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eImitate Peers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e134\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e73.1 (65.2\u0026ndash;80.2, 98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e2.4 (0.3, 66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.9 (0.9, 6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5 (0.4, 35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.7 (0.2, 4.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBeen Independent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e224\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42.0 (35.6\u0026ndash;48.5, 94)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e2.9 (0.4, 49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.0 (1.0, 7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.0 (0.6, 32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.8 (0.2, 4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDrinks WO Help\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e391\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62.4 (57.5\u0026ndash;67.1, 244)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e3.0 (0.3, 153)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.0 (1.2, 6.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.0 (0.3, 108)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (0.2, 6.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUses Utensils With Help\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e429\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e52.9 (48.2\u0026ndash;57.6, 227)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e3.0 (0.2, 131)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.0 (1.3, 7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.6 (0.2, 103)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (0.2, 5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUses Utensils WO Help\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e169\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e73.4 (66.4\u0026ndash;79.7, 124)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e3.0 (0.3, 71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.5 (1.3, 5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.2 (0.2, 50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.7 (0.2, 3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eTable \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eLegend\u003c/span\u003e: The total number (N) of participants with information available on skill loss is shown in the first column. Column two displays the percentage (%), 95% Confidence Interval (CI) and number of individuals (N) who lost a previously gained skill for each skill for all cases. * Indicates where the Clopper-Pearson exact method was used to calculate the CI. The mean age of skill loss in years (yr), with the standard error of the mean (SEM) and the median age of skill loss with 5\u0026ndash;95% intervals are presented for cases with known age of loss. Similarly, for the time from gain to loss the mean, SEM, median and 5\u0026ndash;95% intervals are shown for cases with known age of gain and loss.\u003c/p\u003e\n\u003ch3\u003eRegain of developmental skills\u003c/h3\u003e\n\u003cp\u003eWhile developmental delay and regression are well known features of RTT, it has been recognized that there are instances of regain of previously lost developmental skills in RTT, primarily in the Gross Motor domain [\u003cspan class=\"CitationRef\"\u003e47\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e50\u003c/span\u003e]. For the developmental skills captured, we characterized the percentage of participants who regained each skill and age regained (Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). The range of percentage of regain of individual skills ranged from 2.1% (Play Pat-A-Cake) to 80.6% (Social Smile). For the majority of skills (31 of 51, 60.8%), the percentage of participants who lost and regained that skill was under 20%. In general, low level social and receptive language skills (such as Social Smile, Desire Social Attention, Respond to Own Name) were skills with the highest percentage of regain amongst participants, whereas a low percentage of participants regained higher level skills. The mean age of regaining skills ranged from 2.7 years old (Respond to Sounds) to 8.0 years old (Up Stairs With Help), and the median ranged from 2.0 years old (Respond to Sounds, Attention to Loud Sounds) to 9.0 years old (Up Stairs With Help). Of the 51 developmental skills regained, 46 (90.2%) had a median age of regain under 6 years of age. The percentage of individuals who lost a specific skill and then regained that skill after 6 years of age was under 10% (out of all who lost the skill) for all 51 skills, and 5% or less for 40 of the 51 skills (78.4%). Cumulative incidence curves (Kaplan-Meyer 1-Survival curves) of regain of representative developmental skills are shown in Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e, with regain curves for all developmental skills provided in \u003cstrong\u003eAdditional file 8: Figure \u003cspan class=\"InternalRef\"\u003eS4\u003c/span\u003e\u003c/strong\u003e. Broadly, while there is evidence of skill regain after loss in RTT, the frequency is generally low and typically occurs before 6 years of age.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003e\u003cstrong\u003eDevelopmental Skill Regain\u003c/strong\u003e.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSkill Regain\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eRegain (All Cases)\u003c/span\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eAge Regain (yr)\u003c/span\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eTime Loss to Regain (yr)\u003c/span\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e% Regain\u003c/p\u003e\n \u003cp\u003e(95% CI, N)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003cp\u003e(SEM, N)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian\u003c/p\u003e\n \u003cp\u003e(5%, 95%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e% Regain\u0026thinsp;\u0026gt;\u0026thinsp;6 yo (N)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003cp\u003e(SEM, N)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian\u003c/p\u003e\n \u003cp\u003e(5%, 95%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e% Regain\u0026thinsp;\u0026gt;\u0026thinsp;2yrs post loss (N)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGross Motor\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLift Head\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36.6 (23-51.8, 15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.6 (0.7, 5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.0 (2.0, 6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.8 (0.6, 5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.4 (0.5, 4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15.6 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRoll From Tummy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e400\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14.0 (10.8\u0026ndash;17.6, 56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.3 (0.4, 35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.7 (0.9, 7.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.3 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.4 (0.3, 32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.8 (0.0, 3.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.0 (7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSit With Support\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31.3 (22.0-41.8, 26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.4 (0.6, 14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.0 (1.0, 7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.0 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5 (0.4, 12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (0.2, 3.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.4 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSit Without Support\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e231\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25.1 (19.8\u0026ndash;31.0, 58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.1 (0.5, 43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.0 (1.6, 11.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.0 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.3 (0.4, 41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.0 (0.2, 6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.7 (16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCome To Sit\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e273\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14.3 (10.5\u0026ndash;18.8, 39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.9 (0.7, 29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.5 (1.3, 12.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.9 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.0 (0.5, 28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (0.0, 7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.4 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCrawl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e220\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.5 (2.8\u0026ndash;9.3, 12)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.8 (1.1, 10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.5 (1.8, 12.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.8 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.9 (0.6, 10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.1 (0.3, 6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.4 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStand With Support\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e154\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.7 (7.3\u0026ndash;17.4, 18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.1 (1.4, 12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.0 (1.7, 13.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.0 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.3 (0.8, 11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (0.1, 5.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.5 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePull To Stand\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e350\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.1 (8.1\u0026ndash;14.7, 39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.2 (0.7, 23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.5 (1.6, 12.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.3 (0.4, 22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.7 (0.1, 3.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.4 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWalk With Support\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e251\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16.7 (12.5\u0026ndash;21.7, 42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.5 (0.7, 32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.0 (1.8, 13.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.2 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.0 (0.6, 31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (0.1, 6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.4 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStand Independently\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e119\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.6 (7.5\u0026ndash;19.3, 15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.9 (1.4, 8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.8 (1.7, 12.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.1 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.9 (0.4, 8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.5 (0.1, 3.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.7 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWalk Independently\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e206\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20.4 (15.3\u0026ndash;26.2, 42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.5 (0.7, 30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.3 (1.3, 13.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.8 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.9 (0.2, 28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.7 (0.0, 2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.7 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRan 10 Feet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.8 (3.6\u0026ndash;17.2, 7)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.8 (1.4, 7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.0 (1.7, 12.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.9 (0.3, 7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.8 (0.1, 2.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUp Stairs With Help\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e104\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.5 (7.8\u0026ndash;20.9, 14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.0 (1.2, 9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.0 (3.0, 12.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.3 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.9 (1.2, 9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.2 (0.1, 10.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15.9 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUp Stairs Without Help\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e132\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.8 (5.3\u0026ndash;16.3, 13)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.8 (1.1, 9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.5 (2.0, 12.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.8 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.7 (1.4, 7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.5 (0.4, 10.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.2 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDown Stairs With Help\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.5 (5.9\u0026ndash;19.3, 10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.8 (1.5, 6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.6 (3.0, 12.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.6 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.6 (1.4, 5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.1 (0.1, 8.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.3 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDown Stairs WO Help\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e106\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.5 (4.0-15.5, 9)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.6 (0.8, 3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.6 (5.3, 8.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.2 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.8 (0.7, 3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.3 (2.0, 4.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.9 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eFine Motor\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHold Bottle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e659\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.6 (7.4\u0026ndash;12.1, 63)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.8 (0.4, 48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.1 (1.3, 10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.2 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.7 (0.3, 44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (0.2, 4.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.5 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReach For Toy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e680\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20.6 (17.7\u0026ndash;23.7, 140)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.4 (0.2, 97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.0 (1.5, 6.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5 (7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.7 (0.2, 96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.1 (0.2, 4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.8 (22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRaking Grasp\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e331\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.4 (6.5\u0026ndash;13.0, 31)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.2 (0.4, 19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.0 (1.3, 6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.4 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5 (0.3, 18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (0.2, 4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.6 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTransfer Objects\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e669\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.5 (3.9\u0026ndash;7.5, 37)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.1 (0.5, 28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.0 (1.5, 9.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.9 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.8 (0.3, 27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (0.0, 4.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.8 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePincer Grasp\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e717\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.9 (7.8\u0026ndash;12.3, 71)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.0 (0.4, 48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.0 (1.7, 12.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.5 (12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.2 (0.3, 43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5 (0.3, 6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.0 (14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFinger Feeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e720\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.4 (8.3\u0026ndash;12.8, 75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.0 (0.3, 53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.5 (1.7, 7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.1 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.6 (0.3, 51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (0.2, 4.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.2 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTurn Pages in Book\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e266\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.3 (2.9\u0026ndash;8.7, 14)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.3 (0.8, 6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.5 (2.0, 7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.4 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.9 (0.8, 5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (0.4, 4.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eExpressive\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSocial Smile\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e222\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e80.6 (75.1\u0026ndash;85.5, 179)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.0 (0.2, 137)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.5 (1.1, 6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.6 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.3 (0.2, 133)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.9 (0.2, 3.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.4 (19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCooing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e464\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21.6 (18-25.4, 100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.0 (0.3, 73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.5 (1.2, 6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.2 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5 (0.3, 73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (0.2, 3.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.8 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBabbling\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e647\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28.6 (25.2\u0026ndash;32.2, 185)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.0 (0.2, 154)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.5 (1.3, 6.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.0 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.4 (0.2, 150)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.9 (0.2, 4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.7 (28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWords With Meaning\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e833\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16.6 (14.1\u0026ndash;19.2, 138)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.5 (0.2, 119)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.0 (1.5, 7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.7 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.6 (0.2, 114)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (0.2, 4.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.5 (22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSpoken Phrases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e252\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.9 (6.5\u0026ndash;14.3, 25)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.3 (0.7, 19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.3 (2.0, 9.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.5 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.8 (0.7, 19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5 (0.0, 6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.9 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWave Bye\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e629\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.0 (5.1\u0026ndash;9.3, 44)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.2 (0.3, 30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.0 (1.5, 7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.6 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.7 (0.3, 26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.1 (0.2, 5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePoint for Wants\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e251\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14.3 (10.4\u0026ndash;19, 36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.6 (0.5, 27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.0 (2.0, 9.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.1 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.7 (0.5, 26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.0 (0.5, 7.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.3 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eShared Stories\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.0 (0.3\u0026ndash;44.5, 1)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e- (-, 0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e- (-, 0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eReceptive\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eQuiet To Voice\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e261\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66.7 (60.8\u0026ndash;72.2, 174)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.1 (0.2, 128)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.7 (1.4, 6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.9 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.4 (0.1, 127)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (0.2, 3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14.5 (24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRespond To Sounds\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e79.6 (70.9\u0026ndash;86.7, 78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.7 (0.2, 52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.0 (1.2, 5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.3 (0.2, 50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (0.2, 3.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15.1 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePlay Peek-A-Boo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e229\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.4 (4.4\u0026ndash;11.6, 17)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.1 (0.6, 9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.5 (2.0, 8.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.5 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.8 (0.5, 8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5 (0.3, 3.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.0 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRespond To Words\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e114\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e52.6 (43.5\u0026ndash;61.7, 60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.9 (0.6, 36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.0 (1.5, 8.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.9 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.6 (0.3, 30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (0.2, 5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14.9 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRespond To Own Name\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e108\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e72.2 (63.3\u0026ndash;80.1, 78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.5 (0.4, 52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.8 (1.3, 6.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.7 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.7 (0.4, 45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (0.2, 4.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20.4 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eInhibit To No\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e231\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45.5 (39.1\u0026ndash;51.9, 105)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.9 (0.3, 62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.3 (1.5, 8.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.5 (7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.0 (0.3, 58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5 (0.3, 5.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.0 (14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCommands W Gesture\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e350\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30.6 (25.9\u0026ndash;35.5, 107)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.1 (0.4, 55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.0 (1.6, 9.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.5 (7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.9 (0.3, 54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.2 (0.2, 5.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.6 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCommands WO Gesture\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e272\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31.6 (26.3\u0026ndash;37.3, 86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.9 (0.3, 44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.3 (1.7, 7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.2 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.0 (0.3, 43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5 (0.3, 5.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.3 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIdentify Body Parts\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e124\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14.5 (9.1\u0026ndash;21.4, 18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.5 (0.7, 9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.5 (1.8, 8.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.0 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.2 (0.5, 8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.0 (0.1, 4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.1 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePoint to 1 Color\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32.8 (21.9\u0026ndash;45.1, 20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.9 (1.3, 10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.0 (1.8, 15.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.4 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.3 (1.1, 6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.7 (0.1, 7.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17.4 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSocial/Adaptive\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLike Being Held\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e229\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e73.4 (67.4\u0026ndash;78.8, 168)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.4 (0.2, 139)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.0 (1.2, 7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.6 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.8 (0.2, 136)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.1 (0.2, 4.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24.4 (41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAttention to Sounds\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e109\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e68.8 (59.7\u0026ndash;77, 75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.8 (0.2, 50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.0 (1.0, 6.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.9 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.4 (0.2, 47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (0.2, 4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.8 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEyes Fix and Follow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e345\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e73.6 (68.8\u0026ndash;78.1, 254)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.3 (0.2, 191)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.6 (1.4, 7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.4 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5 (0.1, 182)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (0.2, 4.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16.0 (34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePlay Pat-A-Cake\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e140\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.1 (0.4\u0026ndash;6.1, 3)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.5 (1.5, 2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.0 (5.0, 8.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.8 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.5 (1.5, 2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.0 (2.0, 5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.7 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDesire Social Attention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e72.9 (63.5\u0026ndash;81.1, 70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.0 (0.3, 44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.5 (1.2, 6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.8 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.3 (0.2, 41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0 (0.1, 4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.3 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eImitate Peers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.2 (6.0-18.5, 11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.0 (0.5, 9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.0 (2.2, 6.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.2 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.3 (0.4, 9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.0 (0.8, 4.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.3 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBeen Independent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17.0 (10.4\u0026ndash;25.5, 16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.7 (1.6, 11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.0 (2.0, 8.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.5 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.3 (0.7, 8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.2 (0.3, 6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.1 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDrinks WO Help\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e244\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.6 (5.4\u0026ndash;12.9, 21)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.3 (1.1, 9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.5 (1.8, 12.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.2 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.8 (1, 9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5 (0.4, 8.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.1 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUses Utensils W Help\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e227\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.8 (8.9\u0026ndash;17.5, 29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.5 (0.7, 16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.5 (1.8, 9.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.1 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.3 (0.6, 11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5 (0.3, 4.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.9 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUses Utensils WO Help\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e124\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.9 (4.5\u0026ndash;15.3, 11)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.7 (1.5, 5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.0 (2.0, 10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.2 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.1 (1.3, 5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.5 (0.5, 7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.1 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eTable \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eLegend\u003c/span\u003e: The total number (N) of participants with information available on skill regain is shown in the first column. Column two displays the total percentage (%), 95% Confidence Interval (CI) and number of individuals (N) who regained a previously lost skill for each skill for all cases. * Indicates where the Clopper-Pearson exact method was used to calculate the CI. The mean age of skill regain in years (yr), with the standard error of the mean (SEM) and the median age of skill regain with 5\u0026ndash;95% intervals is presented for cases with identified age of regain. The percentage of individuals (and number) who regained a skill after 6 years old (yo) is shown. Similarly, the mean, SEM, median, and 5\u0026ndash;95% intervals for time from loss to regain in years (yr) is shown as well as the percentage of individuals (and number) who regained a skill more than 2 years after losing that skill is displayed for cases in which the age of loss and regain is known.\u003c/p\u003e\n\u003cp\u003eTo account for variation in the age of loss for specific skills (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e), we calculated the time from loss to regain for each developmental skill (Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). The mean time from loss to regain ranged from 0.9 years (Stand Independently, Walk Independently, Ran 10 Feet) to 4.1 years (Uses Utensils Without Help), and the median time from loss to regain ranged from 0.5 years (Stand Independently, Up Stairs Without Help) to 5.5 years (Uses Utensils Without Help). Nearly all skills had a median time from loss to regain of 2 years or less (46 of 51, 90.2%). For 35 of the 51 developmental skills (68.6%), the percentage of participants who regained that skill (out of all who lost that skill) beyond 2 years from loss was less than 10%, and for 25 of the 51 skills this percentage was less than 5%. Notably, skills with a low percentage of regain beyond 2 years from loss include all the fine motor hand skills (Ranging from 1.5% for Turning Pages in Book to 4.8% for Reach For Toy), more advanced expressive verbal skills such as Words with Meaning (3.5%) or Spoken Phrases (4.9%), and higher-level gross motor skills such as Stand Independently (1.7%) or Walk Independently (0.7%), with the exception of Up Stairs With Help or Down Stairs With Help. In contrast, lower-level skills and non-verbal Receptive skills had a higher percentage of regain beyond 2 years from loss. Cumulative incidence curves (Kaplan-Meyer 1-Survival curves) of the time from loss to regain for representative developmental skills are shown in Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e, with loss to regain curves for all developmental skills provided in \u003cstrong\u003eAdditional file 9: Figure \u003cspan class=\"InternalRef\"\u003eS5\u003c/span\u003e\u003c/strong\u003e. Overall, when skills are regained after loss, for the majority of skills this regain occurs within the first 2 years after loss.\u003c/p\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n \u003ch2\u003eIncidence developmental skill gain or regain in one-year intervals\u003c/h2\u003e\n \u003cp\u003eBecause we observed that developmental skill gain, loss, or regain in RTT primarily occurs within the first couple years of life for the majority of skills (Tables \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e), we were interested in evaluating the incidence of either gaining or regaining a developmental skill in one-year intervals spanning from 0\u0026ndash;20 years old. Figure \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e displays the percentage of eligible participants in each one-year interval who gained or regained a specific developmental skill from age 1\u0026ndash;10 years old. We found that the frequency of gain or regain for any of the skills drops to \u0026lt;\u0026thinsp;2% per year after age 10 (\u003cstrong\u003eAdditional file 9: Figure \u003cspan class=\"InternalRef\"\u003eS6\u003c/span\u003e\u003c/strong\u003e for results spanning the entire age range). For all skills, the one-year incidence of gain or regain is below 4% after 4 years of age. After age 6, the one-year incidence of gain or regain is less than 1% per year for all skills except for Responds To Familiar Words, Responds to Own Name, Point to 1 Color, or Eyes Fix and Follow.\u003c/p\u003e\n \u003cp\u003eWe calculated the frequency of gaining or regaining one or more of any of the 51 skills during one-year intervals (Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e). There is a sharp drop-off in frequency with increasing age, with the overall percentage of eligible participants who gain or regain at least 1 of any of the 51 skills dropping below 6.3% per year after 6 years of life. While this demonstrates that after a given age of life the likelihood of gaining or regaining even one skill becomes unlikely, we were interested if selecting a more limited set of developmental skills would further decrease this likelihood. To evaluate this, we performed a similar analysis on a restricted set of developmental skills, removing early acquired skills for which attainment (either gain or regain) might have limited functional meaningfulness or may have been difficult to clearly assess (\u003cem\u003ee.g\u003c/em\u003e. Lift Head, Quiet to Voice, Respond to Sounds, Social Smile, Like Being Held) or skills with a high rate of gain or regain beyond 3\u0026ndash;4 years old (\u003cem\u003ee.g.\u003c/em\u003e Point to 1 Color). The thirteen skills removed from this restricted analysis are indicated by grey highlights in Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e, leaving the remaining 38 skills for analysis. In this restricted set of developmental skills, the percentage of participants who gained at least one of these 38 skills fell below 5% per year after 6 years of life. This demonstrates that further restriction of which developmental skills to include in an analysis of the one-year incidence of gain or regain of one or more skills, based on consideration of meaningfulness and impact of acquiring a skill on the affected individual, could further decrease the one-year frequency of gain or regain of any of the selected skills.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eAlteration of the developmental trajectory of psychomotor skills (\"developmental milestones\") is a major feature of RTT [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], typically described as \u0026ldquo;apparently normal\u0026rdquo; development in early infancy, followed by developmental delay, subsequent regression of previously acquired skills, and then stabilization with some regain of previously lost skills. Previous studies [\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e, \u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e] primarily presented the proportion of individuals with RTT that gain or lose a skill with limited quantitative information on the timing of skill gain or loss or the proportion and timing of regaining previously lost skills. These gaps reflect the challenge of gathering sufficient data in rare disorders such as RTT. To address these gaps, we analyzed data on developmental skill trajectory in a large cohort (n\u0026thinsp;=\u0026thinsp;1228) of females with Classic RTT collected over the sixteen years from the US RNHS. Our goal was to expand understanding of developmental skill trajectory with granular information on the proportion and timing of skill gain, loss, and regain on a larger set of developmental skills than previously characterized [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] to inform trial design and provide a natural history arm in novel disease modifying therapies for RTT.\u003c/p\u003e\u003cp\u003eThese data are the most exhaustive description of developmental skill trajectory in RTT and are consistent with published findings [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Broadly, we observed a greater percentage of individuals gaining rudimentary skills (acquired earlier in life) than more complex, later-acquired skills. For nearly all the skills assessed (50 of 51), the median age of acquisition (when gained) was under 2 years old, and for over half of the skills (26 of 51), 95% of individuals who gained a specific skill did so by 2 years old. Consistent with this early age of acquisition of skills, \u0026lt;\u0026thinsp;5% of individuals gained any skill after age 4 and \u0026lt;\u0026thinsp;2.5% after 6 years, indicating that gaining a new skill beyond these ages is highly unlikely.\u003c/p\u003e\u003cp\u003eWhile the age of diagnosis of RTT has decreased since the first description of the disorder in English [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e, \u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e], the current median age of diagnosis (2.7 years) [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e] is more than one year after both the previously reported median age of regression (18 months, 1.5 years) [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] and the median age of skill loss reported herein (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Comparing the age of skill acquisition to the expected age (based on CDC developmental milestone surveillance guidelines) [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e] more than half of individuals with RTT did not acquire a specific skill by the CDC guideline threshold age. For nearly all CDC skills (39 of 41), \u0026gt;\u0026thinsp;20% of affected individuals did not obtain a specified skill. Importantly, a significant percentage of individuals with RTT do not obtain major developmental milestones by the age recommended by the CDC guidelines that should occur before the onset of regression (e.g. Pull to Stand, Walk Independently, Pincer Grasp, Words With Meaning). Furthermore, a significant percentage of people with RTT do not acquire many early developmental skills expected to be achieved before 6 months old (e.g. Lift Head, Hold Bottle). These observations have at least two relevant implications. First, if the current CDC surveillance guidelines were universally followed, it is likely that a larger number of individuals with RTT would be identified earlier. Second, it questions the concept that early skill development is \u0026ldquo;apparently normal\u0026rdquo; in RTT [\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e, \u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e], which has been questioned for nearly four decades (see comprehensive review [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]). Families often report that they had suspicion about their child\u0026rsquo;s development even within the first six months of life [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e], and systematic retrospective analysis of early home videos of children subsequently diagnosed with RTT identified characteristic developmental abnormalities [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan additionalcitationids=\"CR58\" citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e]. Hence, earlier genetic testing upon first noticing lack of skill gains could facilitate earlier diagnosis. Development of potentially disease modifying therapies, such as gene therapy, could result in better outcomes with earlier identification. Ultimately, one might argue that newborn screening for pathogenic \u003cem\u003eMECP2\u003c/em\u003e variants could provide rapid, early diagnosis of RTT enabling early interventions; however, this could carry significant risk as the mere presence of pathogenic \u003cem\u003eMECP2\u003c/em\u003e variants is not sufficient to establish the clinical emergence of RTT [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e]. Together, early detection of alterations in early developmental milestones, paired with genetic testing, can lead to specific prediction of which individuals would benefit from early treatment with disease modifying therapies.\u003c/p\u003e\u003cp\u003eA general pattern emerged in our analysis of skill loss. More advanced and later acquired skills are lost in a larger percentage of individuals compared to loss of early developmental skills. For example, the frequency of loss of fine motor skills and expressive communication skills (especially verbal) was high, consistent with the fact that loss of hand skills and verbal communication are defining features of RTT and necessary criteria for the clinical diagnosis of RTT [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Most of the documented skill loss occurs within 2 years of initial gain. However, gross motor skill loss generally occurred over longer time intervals and at older ages than other skill domains (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). This aligns with the concept of \u0026ldquo;Late Motor Decline\u0026rdquo; [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], evaluations focused on longitudinal gross motor performance [\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e, \u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e], and recognition of increasing rigidity and Parkinsonian features with age [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The recognition that regression of most domains (aside from Gross Motor) typically occurs early in life and within the first 2 years after gain is important for counseling and discussion with caregivers. Similarly, acknowledging that loss of previously acquired gross motor skills may occur over a protracted time period and influenced by progressive motor tone abnormalities and Parkinsonian features underscores recommendations for medical interventions that modify tone and long-term physical therapies to maintain gross motor function.\u003c/p\u003e\u003cp\u003eThe period after regression (Stage III, the \u0026ldquo;Pseudostationary\u0026rdquo; stage [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e]) historically has been characterized by the lack of further skill loss, although this has been noted to be invalid [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], and here we demonstrate that slow regression can occur in this stage. Additionally, reports of some degree of regaining lost skills during Stage III exist. While we observed that this can occur, it is rare (\u0026lt;\u0026thinsp;20% of individuals), predominantly in lower-level skills, and infrequent for higher-level skills. Further, regain of skills primarily occurs before age 6 years and within 2 years of loss. Thus, while regaining previously lost skills can occur in RTT, it is uncommon, occurs early in life, shortly after loss, and more frequently for lower-level skills.\u003c/p\u003e\u003cp\u003eAnalysis of the one-year incidence of skill gain or regain demonstrated that individual skill gain or regain occurs early in life and drops off for nearly all skills by age 6 years. Furthermore, the one-year incidence of gaining or regaining at least one of the 51 skills assessed dropped below 10% after age 6 years. Overall, these results indicate that the trajectory of developmental skill gain, loss, and regain in RTT occurs early in life. After age 6 years it is unlikely that a skill not previously obtained will be gained or that a skill previously lost will be regained.\u003c/p\u003e\u003cp\u003eThese results have implications for assessing therapeutic interventions, especially potentially disease-modifying interventions. The ability to describe those skills unlikely to be gained or regained as part of the natural history of RTT could be crucial in establishing reasonable trial outcomes to demonstrate improvement. This is especially critical for clinical trials that preclude conducting studies in a double-blind fashion. Such trials involving gene therapy require invasive procedures in children, utilize vector-based therapies with mortality and morbidity risks, require additional medications such as immunosuppressive agents that carry unacceptable risks in a placebo treated population, and could result in clinical features carrying the risk of unintentional unblinding. The advantages of these developmental endpoints are: 1) they are easily defined, 2) binary, and 3) likely to be emergent with an effective treatment paradigm. Current clinical trial outcome measures such as the Clinical Global Impression of Improvement (CGI-I) [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e] or the Rett Syndrome Behavioral Questionnaire (RSBQ) [\u003cspan additionalcitationids=\"CR65\" citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR66\" class=\"CitationRef\"\u003e66\u003c/span\u003e] have limitations in terms of rater consistency (CGI-I) and limited coverage of important clinical features and sensitivity to change (RSBQ). The ability to apply these real-world natural history data to clinical trials offers a step forward. Importantly, a critical component that recognizes FDA guidance is the consideration of the \u0026ldquo;meaningfulness\u0026rdquo; of the gain or regain of a specific skill [\u003cspan additionalcitationids=\"CR68 CR69 CR70 CR71 CR72\" citationid=\"CR67\" class=\"CitationRef\"\u003e67\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR73\" class=\"CitationRef\"\u003e73\u003c/span\u003e]. The impact of acquiring a skill on the overall quality of life for an affected individual, and their family, is likely not equivalent across the skills evaluated in this study. Gaining/regaining skills that impact adaptive activities, such as walking independently, self-feeding and self-care, and effectively communicating are likely to be more impactful than gaining/regaining lower-level skills such as lifting head or sitting with support. Thus, it is important to determine which skills would be most meaningful through input from those affected and their caregivers. As people with RTT have markedly impaired communication, input from caregivers on meaningfulness of specific skills is critical [\u003cspan additionalcitationids=\"CR68 CR69 CR70 CR71 CR72\" citationid=\"CR67\" class=\"CitationRef\"\u003e67\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR73\" class=\"CitationRef\"\u003e73\u003c/span\u003e]. As demonstrated, limiting the set of developmental skills considered impacts the one-year incidence of either gaining or regaining any of the selected skills. The incorporation of caregiver input to define the most impactful skills, in combination with the expected trajectory of skill gain, loss, and regain, has robust potential to guide clinical trial design and implementation. Furthermore, the rich data provided from this study could be utilized to conduct \u0026ldquo;emulation\u0026rdquo; trials to define the expected trajectory and likelihood of gain or regain in an untreated cohort as a comparator to participants in an open label trial.\u003c/p\u003e\u003cp\u003eAlthough this work presents detailed information gathered from a large cohort of people with RTT, limitations are recognized. First, participants were primarily white, non-Hispanic participants in the US with sufficient resources to participate in this study [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. While efforts were made to maximize participation and representation, the costs, associated loss of income, and difficulties of travel to examination sites could have significantly impacted the composition of the participants. This limits the extrapolation of these findings to other populations, including those outside of the US and from underrepresented populations. Second, the data collected on skill gain, loss, and regain was retrospectively collected from caregivers with the associated potential of recall bias. To mitigate this limitation, every effort was made to encourage families to refer to pictures, videos, baby books, medical records, or association with specific dates such as birthdays or holidays. Further, skill gain, loss, or regain was reviewed at every visit and considered in relation to the current ability of the participant. Because the occurrence of a skill event (gain, loss, or regain) is more likely to be remembered than the specific age of occurrence, we made no attempt to impute missing data for age of event when caregiver recall was not possible. Future studies could employ systematic evaluation of retrospectively captured video data from affected individuals [\u003cspan citationid=\"CR74\" class=\"CitationRef\"\u003e74\u003c/span\u003e] or prospectively captured longitudinal birth cohort studies [\u003cspan citationid=\"CR75\" class=\"CitationRef\"\u003e75\u003c/span\u003e], although the rare occurrence of RTT makes the latter challenging. Despite these limitations, the results presented here based on data collected from more than 1200 individuals with RTT through repeated, in-person assessments represents the largest body of work in this disorder and provides confidence in the reliability and representativeness of these findings. Future studies evaluating genotype/phenotype relationships and development of probabilistic models for the likelihood of individual or multiple skill gain/loss/regain will further expand our understanding of RTT.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn summary, this comprehensive analysis demonstrates that the percentage of individuals with RTT who gain specific skills depends heavily on the developmental level of the skill, with higher-level abilities being acquired by fewer individuals. Skill gain, loss, and regain generally occur early in life, with a developmentally stable period expected after 4\u0026ndash;6 years of age, except for gross motor skills which show a wider age range for skill loss. These natural history data provide fundamental information that can improve our understanding of developmental trajectories in RTT, facilitate earlier diagnosis, inform medical and therapeutic interventions, and guide clinical trial design in RTT.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003eCDC:\u003c/strong\u003e Centers for Disease Control\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCGI-I:\u003c/strong\u003e Clinical Global Impression of Improvement\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCI:\u003c/strong\u003e Confidence Interval\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003edpGAP:\u003c/strong\u003e Database of Genotypes and Phenotypes\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIQR:\u003c/strong\u003e Interquartile Range\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMECP2:\u003c/strong\u003e Methyl-CpG-Binding Protein 2\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eN:\u003c/strong\u003e Number\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNICHD:\u003c/strong\u003e National Institute of Child Health and Development\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRNHS:\u003c/strong\u003e Rett-related disorders Natural History Study\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRSBQ:\u003c/strong\u003e Rett Syndrome Behavioral Questionnaire\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRTT:\u003c/strong\u003e Rett syndrome\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSEM:\u003c/strong\u003e Standard Error of the Mean\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eContributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJLN conceptualized this research, with input from AKP, TAB, EDM, SUP, and CF. JLN, AKP, TAB, EDM, SUP, and CF acquired the data. JLN designed the analysis, compiled and organized the data, and JLN and SKM conducted the analysis of the data. JLN, AKP, TAB, and EDM contributed to interpretation of the data. JLN prepared the draft of the manuscript with input from AKP, TAB, and EDM. All authors participated in reviewing, editing, and revising the initial draft. The authors read and approved the final submitted version.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was supported by funding from the National Institutes of Health grants U54HD061222 (AKP), P50HD103537 (JLN), UL1TR0030396 (the UAB Clinical Translational Research Center), UL1TR002243 (Vanderbilt University Medical Center Clinical Translational Research Center), the International Rett Syndrome Foundation (AKP, JLN), Children\u0026rsquo;s Hospital Colorado Foundation Ponzio Family Chair in Neurology Research (TAB), and the Vanderbilt University Annette Schaffer Eskind Endowed Chair (JLN). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Eunice Kennedy Shriver Child Health and Human Development Institute (NICHD).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets from the Rett syndrome and Rett-related Disorders Natural History Study (RNHS) have been deposited to the database of Genotypes and Phenotypes (dbGAP) repository per a predefined schedule at regular intervals (https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000574.v1.p1). Additionally, the datasets from the RNHS were transferred to the International Rett Syndrome Foundation to facilitate access based on reasonable request to [email protected], pursuant to any required data transfer and use agreements.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics declarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics and Consent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki. All participants or their legally authorized representatives provided written informed consent before participation in the study. The study was approved under a single-IRB provided by the University of Alabama, Birmingham Institutional Review Board (IRB #F150518001). A Certificate of Confidentiality was provided by the National Institute of Child Health and Development (NICHD). This work was not a clinical trial, but the non-interventional observational clinical study protocols were registered with Clinical Trials.Gov (NCT00299312, registration date 06 March 2006, and NCT02738281, registration date 22 November 2015).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJLN received research funding from the National Institutes of Health, the International Rett Syndrome Foundation, and Rett Syndrome Research Trust; clinical trials with Acadia Pharmaceuticals Inc., GW Pharmaceuticals, Ionis Pharmaceuticals, and Taysha Gene Therapies; consultancy paid to his institution from Taysha Gene Therapies; personal consultancy for Acadia Pharmaceuticals Inc., Alcyone Lifesciences, GW Pharmaceuticals, Hoffmann-La Roche, Jazz Pharmaceuticals, Neurogene, Ovid Therapeutics, and Signant Health; and participated on data safety monitoring boards for clinical trials conducted by Ovid Therapeutics and Ultragenyx.\u003c/p\u003e\n\u003cp\u003eAKP received research funding from the National Institutes of Health, the International Rett Syndrome Foundation, and Rett Syndrome Research Trust; participated in clinical trials funded by Acadia Pharmaceuticals and is presently participating in gene therapy trials funded by Taysha Gene Therapies and Neurogene. He is chair of the Data Safety Monitoring Board for the Ionis trial (ION440-CS1) in MECP2 Duplication Syndrome.\u003c/p\u003e\n\u003cp\u003eTAB received research funding from GRIN2B Foundation, the International Foundation for CDKL5 Research, Loulou Foundation, the National Institutes of Health, Rocky Mountain Rett Association, and Simons Foundation; consultancy for Alcyone, AveXis, GRIN Therapeutics, GW Pharmaceuticals, the International Rett Syndrome Foundation, Marinus Pharmaceuticals, Neurogene, Ovid Therapeutics, Takeda Pharmaceutical Company Limited and Taysha; clinical trials with Acadia Pharmaceuticals Inc., GW Pharmaceuticals, IONIS, Marinus Pharmaceuticals, Neurogene, Ovid Therapeutics, and Rett Syndrome Research Trust; all remuneration has been made to his department.\u003c/p\u003e\n\u003cp\u003eEDM received research support from the National Institutes of Health, Penn Orphan Disease Center, the International Rett Syndrome Foundation, Rett Syndrome Research Trust, International CDKL5 Research Foundation, Department of Defense, and the Loulou Foundation. He has been a site principal investigator for trials from Stoke Therapeutics, SK Life, Ionis, Zogenix (now UCB), Acadia Pharmaceuticals Inc., Takeda Pharmaceuticals, Epygenix Pharmaceuticals, and Marinus Pharmaceuticals. He has received personal compensation for consulting and advisory board participation from Acadia, Ionis, Taysha, and Neurogene and the preparation of CME activities for Medscape.\u003c/p\u003e\n\u003cp\u003eSUP received research funding from the National Institutes of Health, the MECP2 Duplication Foundation, and the ActiGraph Corporation. She has been a consultant for Ionis Pharmaceuticals and Taysha Gene Therapies.\u003c/p\u003e\n\u003cp\u003eCF has been a site investigator for clinical trials with Acadia Pharmaceuticals, Zogenix, Ionis Pharmaceuticals, Taysha Gene Therapies, and Neurogene. He has received personal compensation for consulting from Acadia Pharmaceuticals and Taysha Gene Therapies.\u003c/p\u003e\n\u003cp\u003eSKM has no conflicts of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGold WA, Percy AK, Neul JL, Cobb SR, Pozzo-Miller L, Issar JK, et al. Rett syndrome. Nat Rev Dis Primers. 2024;10(1):84.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAmir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet. 1999;23(2):185\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNeul JL, Benke TA, Marsh ED, Skinner SA, Merritt J, Lieberman DN, et al. The array of clinical phenotypes of males with mutations in Methyl-CpG binding protein 2. Am J Med Genet B Neuropsychiatr Genet. 2019;180(1):55\u0026ndash;67.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eThompson T, Gurfinkel D, Silveira L, Klamut N, Ferdinandsen K, Fu C, et al. Medical Biases and Misconceptions Impact Diagnoses in Males With Loss of Function MECP2 Variants. Am J Med Genet A. 2025;197(10):e64147.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHagberg B, Aicardi J, Dias K, Ramos O. A progressive syndrome of autism, dementia, ataxia, and loss of purposeful hand use in girls: Rett's syndrome: report of 35 cases. Ann Neurol. 1983;14(4):471\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNeul JL, Kaufmann WE, Glaze DG, Christodoulou J, Clarke AJ, Bahi-Buisson N, et al. Rett syndrome: revised diagnostic criteria and nomenclature. Ann Neurol. 2010;68(6):944\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHagberg B, Witt-Engerstrom I. Rett syndrome: a suggested staging system for describing impairment profile with increasing age towards adolescence. Am J Med Genet Suppl. 1986;1:47\u0026ndash;59.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCollins BE, Neul JL. Rett Syndrome and MECP2 Duplication Syndrome: Disorders of MeCP2 Dosage. Neuropsychiatr Dis Treat. 2022;18:2813\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHagberg BA. Rett syndrome: clinical peculiarities, diagnostic approach, and possible cause. Pediatr Neurol. 1989;5(2):75\u0026ndash;83.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFitzGerald PM, Jankovic J, Glaze DG, Schultz R, Percy AK. Extrapyramidal involvement in Rett's syndrome. Neurology. 1990;40(2):293\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHumphreys P, Barrowman N. The Incidence and Evolution of Parkinsonian Rigidity in Rett Syndrome: A Pilot Study. Can J Neurol Sci. 2016;43(4):567\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFehr S, Bebbington A, Ellaway C, Rowe P, Leonard H, Downs J. Altered attainment of developmental milestones influences the age of diagnosis of rett syndrome. J Child Neurol. 2011;26(8):980\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNeul JL, Lane JB, Lee HS, Geerts S, Barrish JO, Annese F, et al. Developmental delay in Rett syndrome: data from the natural history study. J Neurodev Disord. 2014;6(1):20.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLee JY, Leonard H, Piek JP, Downs J. Early development and regression in Rett syndrome. Clin Genet. 2013;84(6):572\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEinspieler C, Marschik PB. Regression in Rett syndrome: Developmental pathways to its onset. Neurosci Biobehav Rev. 2019;98:320\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGuy J, Gan J, Selfridge J, Cobb S, Bird A. Reversal of neurological defects in a mouse model of Rett syndrome. Science. 2007;315(5815):1143\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLang M, Wither RG, Colic S, Wu C, Monnier PP, Bardakjian BL, et al. Rescue of behavioral and EEG deficits in male and female Mecp2-deficient mice by delayed Mecp2 gene reactivation. Hum Mol Genet. 2014;23(2):303\u0026ndash;18.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePercy AK, Ananth A, Neul JL. Rett Syndrome: The Emerging Landscape of Treatment Strategies. CNS Drugs. 2024;38(11):851\u0026ndash;67.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePercy AK, Benke TA, Marsh ED, Neul JL. Rett Syndrome: The Natural History Study Journey. Ann Child Neurol Soc. 2024;2(3):189\u0026ndash;205.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNeul JL, Benke TA, Marsh ED, Lane JB, Lieberman DN, Skinner SA, et al. Distribution of hand function by age in individuals with Rett syndrome. Ann Child Neurol Soc. 2023;1(3):228\u0026ndash;38.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNeul JL, Benke TA, Marsh ED, Suter B, Fu C, Ryther RC et al. Clinical Features and Disease Progression in Older Individuals with Rett Syndrome. Genes (Basel). 2024;15(8).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMotil KJ, Geerts S, Annese F, Neul JL, Benke T, Marsh E, et al. Anthropometric Measures Correspond with Functional Motor Outcomes in Females with Rett Syndrome. J Pediatr. 2022;244:169\u0026ndash;77. e3.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCutri-French C, Armstrong D, Saby J, Gorman C, Lane J, Fu C et al. Comparison of core features in four Developmental Encephalopathies in the Rett Natural History Study. Ann Neurol. 2020.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eStallworth JL, Dy ME, Buchanan CB, Chen CF, Scott AE, Glaze DG, et al. Hand stereotypies: Lessons from the Rett Syndrome Natural History Study. Neurology. 2019;92(22):e2594\u0026ndash;603.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBuchanan CB, Stallworth JL, Joy AE, Dixon RE, Scott AE, Beisang AA, et al. Anxiety-like behavior and anxiolytic treatment in the Rett syndrome natural history study. J Neurodev Disord. 2022;14(1):31.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTarquinio DC, Hou W, Neul JL, Berkmen GK, Drummond J, Aronoff E, et al. The course of awake breathing disturbances across the lifespan in Rett syndrome. Brain Dev. 2018;40(7):515\u0026ndash;29.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTarquinio DC, Hou W, Berg A, Kaufmann WE, Lane JB, Skinner SA, et al. Longitudinal course of epilepsy in Rett syndrome and related disorders. Brain. 2017;140(2):306\u0026ndash;18.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKillian JT, Lane JB, Cutter GR, Skinner SA, Kaufmann WE, Tarquinio DC, et al. Pubertal development in Rett syndrome deviates from typical females. Pediatr Neurol. 2014;51(6):769\u0026ndash;75.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSaby JN, Mulcahey PJ, Benke TA, Peters SU, Standridge SM, Lieberman DN, et al. Electroencephalographic Correlates of Clinical Severity in the Natural history study of RTT and Related Disorders. Ann Neurol. 2024;96(1):175\u0026ndash;86.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSaby JN, Peters SU, Benke TA, Standridge SM, Swanson LC, Lieberman DN, et al. Comparison of evoked potentials across four related developmental encephalopathies. J Neurodev Disord. 2023;15(1):10.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSaby JN, Benke TA, Peters SU, Standridge SM, Matsuzaki J, Cutri-French C, et al. Multisite Study of Evoked Potentials in Rett Syndrome. Ann Neurol. 2021;89(4):790\u0026ndash;802.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNeul JL, Skinner SA, Annese F, Lane J, Heydemann P, Jones M, et al. Metabolic Signatures Differentiate Rett Syndrome From Unaffected Siblings. Front Integr Neurosci. 2020;14:7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMotil KJ, Barrish JO, Lane J, Geerts SP, Annese F, McNair L, et al. Vitamin d deficiency is prevalent in girls and women with rett syndrome. J Pediatr Gastroenterol Nutr. 2011;53(5):569\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRaspa M, Gwaltney A, Bann C, von Hehn J, Benke TA, Marsh ED, et al. Psychometric Assessment of the Rett Syndrome Caregiver Assessment of Symptom Severity (RCASS). J Autism Dev Disord. 2025;55(3):997\u0026ndash;1009.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNeul JL, Benke TA, Marsh ED, Suter B, Silveira L, Fu C, et al. Top caregiver concerns in Rett syndrome and related disorders: data from the US natural history study. J Neurodev Disord. 2023;15(1):33.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRaspa M, Bann CM, Gwaltney A, Benke TA, Fu C, Glaze DG, et al. A Psychometric Evaluation of the Motor-Behavioral Assessment Scale for Use as an Outcome Measure in Rett Syndrome Clinical Trials. Am J Intellect Dev Disabil. 2020;125(6):493\u0026ndash;509.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLane JB, Salter AR, Jones NE, Cutter G, Horrigan J, Skinner SA, et al. Assessment of Caregiver Inventory for Rett Syndrome. J Autism Dev Disord. 2017;47(4):1102\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKillian JT Jr., Lane JB, Lee HS, Pelham JH, Skinner SA, Kaufmann WE, et al. Caretaker Quality of Life in Rett Syndrome: Disorder Features and Psychological Predictors. Pediatr Neurol. 2016;58:67\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNeul JL, Glaze DG, Percy AK, Feyma T, Beisang A, Dinh T, et al. Improving Treatment Trial Outcomes for Rett Syndrome: The Development of Rett-specific Anchors for the Clinical Global Impression Scale. J Child Neurol. 2015;30(13):1743\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLane JB, Lee HS, Smith LW, Cheng P, Percy AK, Glaze DG, et al. Clinical severity and quality of life in children and adolescents with Rett syndrome. Neurology. 2011;77(20):1812\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNeul JL, Percy AK, Benke TA, Berry-Kravis EM, Glaze DG, Marsh ED, et al. Trofinetide for the treatment of Rett syndrome: a randomized phase 3 study. Nat Med. 2023;29(6):1468\u0026ndash;75.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNeul JL, Fang P, Barrish J, Lane J, Caeg EB, Smith EO, et al. Specific mutations in methyl-CpG-binding protein 2 confer different severity in Rett syndrome. Neurology. 2008;70(16):1313\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCuddapah VA, Pillai RB, Shekar KV, Lane JB, Motil KJ, Skinner SA, et al. Methyl-CpG-binding protein 2 (MECP2) mutation type is associated with disease severity in Rett syndrome. J Med Genet. 2014;51(3):152\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZubler JM, Wiggins LD, Macias MM, Whitaker TM, Shaw JS, Squires JK et al. Evidence-Informed Milestones for Developmental Surveillance Tools. Pediatrics. 2022;149(3).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePercy AK, Neul JL, Ananth A, Benke TA, Marsh ED. Symptom Onset in Classic Rett Syndrome: Analysis of Initial Clinical Severity Scale Entries. Ann Child Neurol Soc; 2025.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTarquinio DC, Hou W, Neul JL, Lane JB, Barnes KV, O'Leary HM, et al. Age of diagnosis in Rett syndrome: patterns of recognition among diagnosticians and risk factors for late diagnosis. Pediatr Neurol. 2015;52(6):585\u0026ndash;91. e2.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRomano A, Rodocanachi Roidi ML, Savini MN, Vigano I, Dziubak M, Pietrogrande L et al. Effects of a Supervised-As-Needed Home Exercise Program on Scoliosis and Motor Function in Rett Syndrome: A Multiple-Baseline Study. J Clin Med. 2025;14(6).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCapri T, Dovigo L, Semino M, Lotan M, Mohammadhasani N, Zamarra G, et al. Use of a low-tech tool in the improvement of social interaction of patients with Rett Syndrome: an observational study. Front Public Health. 2024;12:1353099.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKapel A, Kovacic T, Kos N, Velnar T. Impact of a 12-month multifaceted neurological physiotherapy intervention on gross motor function in women with Rett syndrome. J Integr Neurosci. 2022;21(2):59.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRomano A, Ippolito E, Favetta M, Lotan M, Moran DS. Individualized Remotely Supervised Motor Activity Programs Promote Rehabilitation Goal Achievement, Motor Functioning, and Physical Activity of People with Rett Syndrome-A Single-Cohort Study. Int J Environ Res Public Health. 2022;20(1).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCass H, Reilly S, Owen L, Wisbeach A, Weekes L, Slonims V, et al. Findings from a multidisciplinary clinical case series of females with Rett syndrome. Dev Med Child Neurol. 2003;45(5):325\u0026ndash;37.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLarsson G, Lindstrom B, Engerstrom IW. Rett syndrome from a family perspective: The Swedish Rett Center survey. Brain Dev. 2005;27(Suppl 1):S14\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFehr S, Bebbington A, Nassar N, Downs J, Ronen GM. Trends in the diagnosis of Rett syndrome in Australia. Pediatr Res. 2011;70(3):313\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRett A. On a remarkable syndrome of cerebral atrophy associated with hyperammonaemia in childhood. Wien Med Wochenschr. 2016;166(11\u0026ndash;12):322\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHagberg B, Goutieres F, Hanefeld F, Rett A, Wilson J. Rett syndrome: criteria for inclusion and exclusion. Brain Dev. 1985;7(3):372\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBisgaard AM, Schonewolf-Greulich B, Ravn K, Ronde G. Is it possible to diagnose Rett syndrome before classical symptoms become obvious? Review of 24 Danish cases born between 2003 and 2012. Eur J Paediatr Neurol. 2015;19(6):679\u0026ndash;87.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEinspieler C, Kerr AM, Prechtl HF. Abnormal general movements in girls with Rett disorder: the first four months of life. Brain Dev. 2005;27(Suppl 1):S8\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEinspieler C, Sigafoos J, Bolte S, Bratl-Pokorny KD, Landa R, Marschik PB. Highlighting the first 5 months of life: General movements in infants later diagnosed with autism spectrum disorder or Rett Syndrome. Res Autism Spectr Disord. 2014;8(3):286\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEinspieler C, Freilinger M, Marschik PB. Behavioural biomarkers of typical Rett syndrome: moving towards early identification. Wien Med Wochenschr. 2016;166(11\u0026ndash;12):333\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSuter B, Treadwell-Deering D, Zoghbi HY, Glaze DG, Neul JL. Brief Report: MECP2 Mutations in People Without Rett Syndrome. J Autism Dev Disord. 2013.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFoley KR, Downs J, Bebbington A, Jacoby P, Girdler S, Kaufmann WE, et al. Change in gross motor abilities of girls and women with rett syndrome over a 3- to 4-year period. J Child Neurol. 2011;26(10):1237\u0026ndash;45.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBisgaard AM, Wong K, Hojfeldt AK, Larsen JL, Schonewolf-Greulich B, Ronde G, et al. Decline in gross motor skills in adult Rett syndrome; results from a Danish longitudinal study. Am J Med Genet A. 2021;185(12):3683\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHagberg B. Clinical manifestations and stages of Rett syndrome. Ment Retard Dev Disabil Res Rev. 2002;8(2):61\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePercy AK, Neul JL, Benke TA, Marsh ED, Glaze DG. A review of the Rett Syndrome Behaviour Questionnaire and its utilization in the assessment of symptoms associated with Rett syndrome. Front Pediatr. 2023;11:1229553.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDowns J, Wong K, Leonard H. Associations between genotype, phenotype and behaviours measured by the Rett syndrome behaviour questionnaire in Rett syndrome. J Neurodev Disord. 2024;16(1):59.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKaufmann WE, Oberman LM, Downs J, Leonard H, Barnes KV. Rett Syndrome Behaviour Questionnaire: Variability of Scores and Related Factors. J Child Adolesc Psychopharmacol. 2025;35(7):388\u0026ndash;98.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAdministration FaD. Patient-Focused Drug Development: Incorporating Clinical Outcome Assessments Into Endpoints for Regulatory Decision-Making, draft guidance. In: Services UDoHaH, editor. 2023.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eConnor-Ahmad S, Tjeertes J, Chladek M, Newton L, Symonds T, Clinch S, et al. Developing Angelman syndrome-specific clinician-reported and caregiver-reported measures to support holistic, patient-centered drug development. Orphanet J Rare Dis. 2023;18(1):156.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGizzo L, Bliss G, Palaty C, Kolevzon A. Caregiver perspectives on patient-focused drug development for Phelan-McDermid syndrome. Orphanet J Rare Dis. 2024;19(1):134.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDowns J, Ludwig NN, Wojnaroski M, Keeley J, Schust Myers L, Chapman CAT, et al. What does better look like in individuals with severe neurodevelopmental impairments? A qualitative descriptive study on SCN2A-related developmental and epileptic encephalopathy. Qual Life Res. 2024;33(2):519\u0026ndash;28.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHecker J, Conecker G, Chapman C, Hommer R, Ludwig NN, Sevinc G, et al. Patient-advocate-led global coalition adapting fit-for-purpose outcomes measures to assure meaningful inclusion of DEEs in clinical trials. Ther Adv Rare Dis. 2024;18:26330040241249762.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDowns J, Haywood S, Ludwig NN, Wojnaroski M, Hommer R, Muzyczka K et al. Caregiver-reported meaningful change in functional domains for individuals with developmental and epileptic encephalopathy: A convergent mixed-methods design. Dev Med Child Neurol. 2025.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKeeley J, Skoda Z, Utley K, Marsh ED, Conecker GA, Hecker J et al. Parent/caregiver perspectives of meaningful improvement in functional domains for people with CDKL5 deficiency disorder: a mixed-methods study. Qual Life Res. 2025.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePokorny FB, Schmitt M, Egger M, Bartl-Pokorny KD, Zhang D, Schuller BW, et al. Automatic vocalisation-based detection of fragile X syndrome and Rett syndrome. Sci Rep. 2022;12(1):13345.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMarschik PB, Lemcke S, Einspieler C, Zhang D, Bolte S, Townend GS, et al. Early development in Rett syndrome - the benefits and difficulties of a birth cohort approach. Dev Neurorehabil. 2018;21(1):68\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-neurodevelopmental-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jndd","sideBox":"Learn more about [Journal of Neurodevelopmental Disorders](http://jneurodevdisorders.biomedcentral.com/)","snPcode":"11689","submissionUrl":"https://submission.nature.com/new-submission/11689/3","title":"Journal of Neurodevelopmental Disorders","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Rett syndrome, Developmental milestones, Gain/Loss/Regain, Natural History Study, Clinical trial endpoint","lastPublishedDoi":"10.21203/rs.3.rs-8245192/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8245192/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eTo characterize frequency, timing, and trajectory of gain, loss, and regain of developmental skills in Classic Rett syndrome (RTT).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThe frequency and timing of gain, loss, and regain of 51 developmental skills from 1228 females with Classic RTT and a pathogenic loss-of-function variant in \u003cem\u003eMECP2\u003c/em\u003e was assessed during in-person visits from participants enrolled in the US Natural History Study. The percentage of participants experiencing gain, loss, or regain events, mean and median age of event and time to event with confidence intervals, and the cumulative incidence curves were calculated and compared to normative data using SPSS v29.0.2.0. One-year incidence of either gain or regain of each skill from 0\u0026ndash;20 years old and one-year incidence of either gain or regain of any of 51 developmental skills was calculated.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eThe acquisition of skills was greatest for lower-level skills and conversely lowest for more advanced skills. Acquisition of skills peaked at 6 years. Skill loss occurred mainly within 2 years of acquisition. Loss of fine motor, communication, and social adaptive skills changed little after age 6 years. The regain of lost skills involved less than 30% of fine motor, communication, and social adaptation. Regain of skills generally ceased by age 6 years.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eThese results provide critical endpoints essential for conducting clinical trials in RTT. The lack of acquisition of skills beyond age 6 years and absence of loss or regain of previously lost skills, aside from gross motor features, beyond 6 years suggest that functional gains in these realms would represent important indicators of efficacy.\u003c/p\u003e","manuscriptTitle":"Trajectory of skill acquisition, loss, and regain in females with classic Rett syndrome","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-15 01:08:01","doi":"10.21203/rs.3.rs-8245192/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-02-05T14:47:09+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-05T13:27:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"73750288041431954057318433527803990713","date":"2026-01-20T09:26:18+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-16T12:59:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"93754200409225188839681467180710575831","date":"2026-01-12T05:10:46+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-12-09T15:09:33+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-12-03T12:28:29+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-03T12:28:19+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Neurodevelopmental Disorders","date":"2025-12-01T02:00:39+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-neurodevelopmental-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jndd","sideBox":"Learn more about [Journal of Neurodevelopmental Disorders](http://jneurodevdisorders.biomedcentral.com/)","snPcode":"11689","submissionUrl":"https://submission.nature.com/new-submission/11689/3","title":"Journal of Neurodevelopmental Disorders","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f9606081-66ac-422b-a1d3-b55767bd818e","owner":[],"postedDate":"December 15th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-03-16T16:08:01+00:00","versionOfRecord":{"articleIdentity":"rs-8245192","link":"https://doi.org/10.1186/s11689-026-09680-6","journal":{"identity":"journal-of-neurodevelopmental-disorders","isVorOnly":false,"title":"Journal of Neurodevelopmental Disorders"},"publishedOn":"2026-03-12 15:59:51","publishedOnDateReadable":"March 12th, 2026"},"versionCreatedAt":"2025-12-15 01:08:01","video":"","vorDoi":"10.1186/s11689-026-09680-6","vorDoiUrl":"https://doi.org/10.1186/s11689-026-09680-6","workflowStages":[]},"version":"v1","identity":"rs-8245192","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8245192","identity":"rs-8245192","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}