Life-cycle management of fetal short femur length caused by achondroplasia: A case report

Life-cycle management of fetal short femur length caused by achondroplasia: A case report | 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 Life-cycle management of fetal short femur length caused by achondroplasia: A case report Qing Zhou, huaxiang Zhong, Qingsong Wu, Xu Luo, xueqin Lu, Wenjie Cong This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5868024/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Achondroplasia (ACH) is the most common non-lethal skeletal dysplasia and can lead to short femur length (FL), which is uncommon in the pediatric setting. This case report describes a case of fetal short FL caused by ACH, which was detected by routine ultrasonography during the 26th week of gestation in a 24-year-old woman. Based on the theory of the Bowen family system, the study followed the fetus and her family for 2.5 years, observed and analyzed the growth and development of the fetus, and provided psychological support to the family. In cases like this, life-cycle management is crucial and beneficial to ensure the healthy development and growth of the fetus with short femur length in the long term. achondroplasia life-cycle management short femur length short limbs Figures Figure 1 Figure 2 Introduction Femur length (FL) is an important index for evaluating fetal intrauterine growth and development and screening skeletal system malformation 1 . A short FL, defined as fetal FL below the 5th percentile or − 2 standard deviations (SD) for gestational age by ultrasound, marks aneuploidy or skeletal dysplasia 2 . Other concurrent abnormalities, such as macrocephaly, forehead protrusion, midface dysplasia, flat nose bridge, "three-pronged hand," and excessive amniotic fluid, can also assist the diagnosis. It can be caused by physiological factors, such as heredity, normal small for gestational age infant (nSGA), and pathological factors, such as abnormal skeletal development system, fetal chromosome abnormality, and fetal growth restriction (FGR) 1 . Achondroplasia (ACH) is the most common non-lethal skeletal dysplasia in fetuses, with an incidence rate of 1.3 ~ 6.0 per 100,000 populations 3 , 4 . It mainly affects the growth of long bones in fetal limbs after 25 weeks of gestation 5 . ACH is primarily caused by fibroblast growth factor receptor 3 (FGFR3) gene mutation located on chromosome 4p16. 3 6,7 . Most patients present with C.1138G > A mutation, while a few show nucleotide C.1 138G > C mutation, leading to the encoded amino acid at position380 changing from glycine (Gly) to arginine (Arg) 6 , 7 . Therefore, the gold standard for ACH diagnosis is a mutation at 1138 nucleotides of the FGFR3 gene. In this study, a fetus with short FL caused by ACH was detected by routine ultrasonography during the 26th week of gestation in a 24-year-old woman who decided to continue the pregnancy and keep the baby. The fetus and her family were followed up for 2.5 years. A family-centered evaluation and follow-up schedule was established to analyze all B-ultrasound results, postnatal genetic test results, and early childhood growth and development. Our study would provide a reference and suggestions for family-oriented life-cycle management of fetal short FL caused by ACH. Case report A pregnant woman with the last menstruation on January 16, 2020, and an expected date of delivery on October 22, 2020, was detected with fetal short FL in the early pregnancy B-ultrasound on March 5, 2020. After being told the prognosis, the pregnant woman and her family decided to deliver the baby. The fetus and her family were followed up from 26 gestational weeks to May 2023. All clinical information of the pregnant women during the whole gestational period was collected, including blood tests, Down's screening, non-invasive DNA, N-TB super loading, etc. The baby's clinical information at birth was also collected, including Apgar score, height, weight, body surface deformity, head size and shape, mouth cleft lip and palate, neck symmetry, range of motion, and thorax shape. The ACH-specific growth parameter registry (height, body mass, head circumference) at birth and weeks 1, 2, 4, and 6 was used for longitudinal monitoring 8 , 9 . The baby was later followed up once a month from Month 2 to Month 12, then every two months till age 2.5 years, and every three months thereafter. The following measurement indexes of ultrasound screening were recorded: Ratio of FL to HC (FL/HC), ratio of FL to AC (FL/AC), Z-value of FL (ZFL), Z-value of HC (ZHC), Z-value of AC (ZAC), the subtraction between the ∆ZH-F = ZHC-ZFL, as ZAC and the difference between the ZFL and delta useful - F [useful + A - F = 2 e = (ZHC - ZFL) + (ZAC - ZFL) = ZHC + ZAC − 2 ZFL]. Z-value = (measured value - standard value for the gestational age)/ standard deviation (SD). The standard values and SDs for the gestational age were based on Leung et al.'s fetal biometric standards of the Chinese population 10 . FL/HC and FL/AC are indicators for fetal growth and development and can be used to predict adverse pregnancy outcomes. The normal values of FL/HC and FL/AC in fetuses from 22 to 34 weeks of gestation are 0.193–0.207 and 0.199–0.205, respectively 11 . FL/AC < 0.160 is helpful in predicting fatal fetal bone dysplasia 9 . ZFL, ZHC, and ZAC represent the SD multiples of the difference between the fetal FL, HC, and AC values and the corresponding gestational week standard values. ZFL 2.00 indicates a large head. ∆ZH-F indicates the SD multiple of femur development relative to head development. ∆ZH + A-2F indicates the SD multiple of femur development relative to head and abdominal development lag, with a higher value indicating a higher risk of genetic abnormalities in the fetus 12 . Sanger sequencing detected mutant genes in the sampled peripheral blood of the fetus (female) and its parents 7 months after birth (Table 1 ). The sequencing data were analyzed by MutiationsSurveyor software developed by SoftGenetics Company. Children's physical growth measurement tools, methods, and precautions were based on the recommendations proposed by the Group of Child Health Care, Society of Pediatrics, Chinese Medical Association 13 , 14 . Table 2. Prenatal fetal ultrasound and index analysis results GW BPD（mm） HC（mm） AC (mm) FL （mm） Z BPD Z HC Z AC Z FL FL/HC FL/AC ∆Z H-F ∆Z H+A+2F 12 22 54 66 8 -12.20 -7.66 -5.55 -11.94 0.15 0.12 4.28 10.67 17 34 132 109 20 -20.40 -3.63 -7.13 -28.36 0.15 0.18 24.73 45.96 24 54 202 175 34 -21.44 -20.23 -12.28 -46.68 0.17 0.19 26.45 60.86 26 61 230 205 38 -18.71 -9.92 -10.30 -50.47 0.16 0.17 40.55 80.73 28 70 254 228 39.8 -7.58 -4.32 -0.51 -62.74 0.16 0.17 58.42 120.64 30 78 277 250 43 -0.93 2.12 0.96 -65.41 0.16 0.17 67.53 133.91 32 85 305 270 46 9.99 15.61 6.05 -79.19 0.15 0.17 94.80 180.04 33 90 316 278 46 14.98 18.56 0.15 -81.96 0.15 0.17 100.52 182.62 36 93 334 326 49 14.24 15.05 21.37 -84.08 0.15 0.15 99.13 204.58 37 97 336 334 50 20.15 28.79 21.47 -85.02 0.15 0.15 113.81 220.30 39 100 347 356 50 22.30 7.82 26.69 -92.36 0.14 0.14 100.18 219.22 Table 3. Basic physical development of the baby from birth to 24 months Interval weight(g) weight Median Length ( cm ) length Median head circumference ( cm ) head circumference Median At birth 3540 - 46 - 35.2 1wks 3652 879 47 8.5 35.62 4.4 2wks 3790 48.5 36.3 3wks 4136 49.3 36.45 4wks 4480 50.2 36.9 1-2mo 4762 744 51.5 37.9 2-3 mo 5248 718 53.8 3.5 38.47 1.55 3-4 mo 6102 585 54.4 2.8 39.2 1.15 4-5 mo 6630 489 55.6 2.25 39.8 1 5-6 mo 7038 401 57 1.85 40.73 0.95 6-7 mo 7438 344 58 1.5 41.3 0.7 7-8 mo 7750 311 58.7 1.4 41.98 0.6 8-9 mo 8010 273 59.5 1.35 42.65 0.5 9- 10 mo 8238 245 60 1.3 43.1 0.4 10- 11 mo 8520 233 61.5 1.25 43.58 0.35 11- 12 mo 8652 232 63.5 1.2 44.26 0.35 12-14mo 9089 437 64.8 2.3 44.67 0.25 14-16mo 9430 401 65.2 2.1 45.2 0.25 16-18mo 9801 401 65.8 2 46.3 0.17 18-20mo 10109 393 66.1 1.9 47.1 0.17 20-22mo 10528 382 66.6 1.8 48.8 0.1 22-24mo 10987 376 67 1.7 49 0.1 At 26 weeks of prenatal ultrasound screening, the pregnant woman was informed that the fetus had short limbs. The femur length was 50.47 SD lower than the normal value, the biparietal diameter was 18.71 SD lower than the normal value, FL/HC was 0.16, lower than the normal value (0.193–0.207), and FL/AC was 0.17. All B-ultrasound results during pregnancy were collected. Specific data are shown in Table 2 & Fig. 1 . Sequencing analysis of disease-related genes identified highly suspicious variants associated with the disease phenotype. A heterozygous mutation in the FCFR3 gene was found. c.1138G > A (p.G380R), and there was no variation in this site in either parent of the baby. The specific variation is unknown in the heterozygous mutation of nucleotide 1138 from guanine G to adenine A (c.1138G > A), resulting in amino acid 380 from glycine to arginine (p.G380R). The results of the ACMG family gene analysis are shown in Fig. 2 . The medical team monitored the baby's general development, including the height, weight, and head circumference, from birth to 24 months of age, according to the 2009 WHO Child Growth Standards (2009 WHO). The results are shown in Table 3 . Discussion The diagnosis of short FL is mainly based on B-ultrasound, which is a routine prenatal examination for the initial diagnosis of fetal femur microsomia. However, B-ultrasound can only diagnose short FL after 26 weeks of gestation since the fetal skeletal system has not yet fully formed during early pregnancy. Before the molecular diagnosis of ACH became a routine clinical program, ultrasound still maintained the primary method for prenatal diagnosis of ACH 15 . In this study, the fetus had short FL at 12 weeks of gestation, which was about 11 SD lower than the normal standard. ZHC > 6 after 32 weeks, indicating a large head circumference. ∆ZH-F was 4.28-100.18 SD multiples, suggesting that femur development lagged severely behind head development. The values of ∆ZH + A-2F were in the range of 10.67-219.22 SD multiples, which also revealed that the femur development lagged severely behind the head and abdomen, suggesting a high risk of genetic abnormalities in the fetus. ACH is caused by mutations in FGFR3 (4p16.3), a gene encoded by fibroblast growth factor receptor-3 (FGFR3). 98% of ACH patients carry the FGFR3c.1138G > A mutation, and 1% carry the FGFR3 C.1138G > C mutation, both can cause glycine replacement to arginine (G380R) in the 380th transmembrane region of FGFR3 16 . The case in this study is consistent with those reported in the literature. Studies have shown that ACH is an autosomal dominant genetic disease with 100% penetrance, which can cause death in the early embryo or at birth or within 1 year after birth due to severe chondroid developmental disorder. This case was non-fatal ACH, and the child had grown to 30 months by June 2023. No case of a "three-pronged hand" was found, but the child had a short root form of limbs, which was consistent with the literature 17 . Most ACH mutations are heterozygous, and 80% of them are sporadic cases with normal parental phenotypes, which is also the case in this study. Both parents of the patient showed normal phenotypes, and there were no ACH cases in the three generations of the child's ancestors, suggesting a sporadic ACH. Most of the pathogenic genes of ACH come from the father and show a typical paternal age effect. The risk of ACH increases by 5.0 times when the paternal age is ≥ 40 years and by 10 times when the paternal age is over 50 years old 18 . In this case, the patient's father was exactly 40 years old when she was born, which may indicate the paternal age effect. The patient's mom did not have any disease or receive any drug treatment during the first three months of pregnancy. All prenatal blood tests at 6 weeks of pregnancy were normal except for a history of rubella virus infection, which presented no symptoms and required no further treatment. On May 7, 2020, the mom underwent Down's screening, non-invasive DNA, and N-TB ultrasounds, all indicated no abnormalities, further proving that ACH was caused by heterozygous mutations. The Apgar score of the patient at birth was 10, which basically ruled out fatal dwarfism and other skeletal problems. At birth, she was 46cm in height and 3540g in weight, with no deformity or abnormality. The patient's height was close to the percentile value P10 (51.6) in the first month after birth and was lower than the standard in the next 24 months. According to the recommendations of the Child Health Group of the Pediatrics Society of the Chinese Medical Association, the mean ± 2S or the 3–97 percentile (P) is considered the normal range. The 24-month head circumference was located between P90 and P97 (49.8), which means a significant larger size of the head, and the limbs were shorter than normal. In this period, the teamwork aimed at helping the family to accept the reality and embrace the baby as she is. According to the Bowen family system, a emotional fusion and differentiation underscores the significance of emotional supports in relationships. The body mass index for age (BMI/ age) at the 24th month was calculated to be 24.48, exceeding 3SD (20.4), and the family was reminded to strictly control the child's weight and reduce the intake of high-calorie food. In addition, a skull and thoracolumbar MR plan was developed to monitor the progressing of hydrocephalus and thoracolumbar compression in child. The study applied the theory of the Bowen family system, which viewed the family as an emotional unit and used system thinking to describe its complex interactions 8 , 19 , 20 No mental abnormalities were observed in the patient from birth to 2.5 years of age, which was consistent with the main symptoms of ACH described by Marie 21 . During this period, the patient's family has been looking for appropriate treatment plans. According to the family's willingness, Chinese medicine therapy would be considered for future treatment. In this regard, the life cycle management of family-oriented practice services will be continued in this study to serve the family. Declarations Ethics approval and consent to participate: The study was approved by the Ethics Committee of the First Affiliated Hospital of Wenzhou Medical University（KY2023-R187） Before initiating the study, the researchers engaged in communication with the participant's mother. Detailed information was provided, including its objectives, the methods that would be employed, and the potential risks and benefits involved. The researchers then obtained written consent from her mother, which served as a formal record of the participant's agreement to take part in the study. Consent for publication The consent for publication had been obtained from the mother. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing interests: The authors declare that they have no competing interests. Funding: Not applicable References D'Ambrosio, V. et al. Midtrimester isolated short femur and perinatal outcomes: A systematic review and meta-analysis. Acta Obstet Gynecol Scand 98 , 11-17 (2019). https://doi.org:10.1111/aogs.13470 Papageorghiou, A. T., Fratelli, N., Leslie, K., Bhide, A. & Thilaganathan, B. Outcome of fetuses with antenatally diagnosed short femur. Ultrasound Obstet Gynecol 31 , 507-511 (2008). https://doi.org:10.1002/uog.5265 Neumeyer, L., Merker, A. & Hagenäs, L. Clinical charts for surveillance of growth and body proportion development in achondroplasia and examples of their use. Am J Med Genet A 185 , 401-412 (2021). https://doi.org:10.1002/ajmg.a.61974 Chitty, L. S. et al. New aids for the non-invasive prenatal diagnosis of achondroplasia: dysmorphic features, charts of fetal size and molecular confirmation using cell-free fetal DNA in maternal plasma. Ultrasound Obstet Gynecol 37 , 283-289 (2011). https://doi.org:10.1002/uog.8893 Merker, A. et al. Development of body proportions in achondroplasia: Sitting height, leg length, arm span, and foot length. Am J Med Genet A 176 , 1819-1829 (2018). https://doi.org:10.1002/ajmg.a.40356 Stoll, C., Dott, B., Roth, M. P. & Alembik, Y. Birth prevalence rates of skeletal dysplasias. Clin Genet 35 , 88-92 (1989). https://doi.org:10.1111/j.1399-0004.1989.tb02912.x Tofts, L., Das, S., Collins, F. & Burton, K. L. O. Growth charts for Australian children with achondroplasia. Am J Med Genet A 173 , 2189-2200 (2017). https://doi.org:10.1002/ajmg.a.38312 Hoover-Fong, J., Scott, C. I. & Jones, M. C. Health Supervision for People With Achondroplasia. Pediatrics 145 (2020). https://doi.org:10.1542/peds.2020-1010 Rahemtullah, A., McGillivray, B. & Wilson, R. D. Suspected skeletal dysplasias: femur length to abdominal circumference ratio can be used in ultrasonographic prediction of fetal outcome. Am J Obstet Gynecol 177 , 864-869 (1997). https://doi.org:10.1016/s0002-9378(97)70284-9 Hadlock, F. P., Harrist, R. B., Shah, Y. & Park, S. K. The femur length/head circumference relation in obstetric sonography. J Ultrasound Med 3 , 439-442 (1984). https://doi.org:10.7863/jum.1984.3.10.439 Herrera, C. L., Hussamy, D. J., McIntire, D. D., Twickler, D. M. & Dashe, J. S. Femur length parameters in fetuses with Down syndrome†. J Matern Fetal Neonatal Med 33 , 2516-2521 (2020). https://doi.org:10.1080/14767058.2018.1554047 Crane, H. M. et al. The Reliability of Ultrasound Markers in Identifying Fetuses With a Life-Limiting Skeletal Dysplasia. Prenat Diagn 44 , 1318-1326 (2024). https://doi.org:10.1002/pd.6638 [Expert consensus on clinical practice of assessment and management of childhood physical development]. Zhonghua Er Ke Za Zhi 59 , 169-174 (2021). https://doi.org:10.3760/cma.j.cn112140-20210116-00050 YH., Z. Analysis of causes and nursing intervention measures of accidental tube withdrawal in patients with external thoracic surgery. Chinese Remedies & Clinics 21 , 1041-1043 (2021). https://doi.org:DOI:10.11655/zgywylc2021.06.068 Fredwall, S. et al. Optimising care and follow-up of adults with achondroplasia. Orphanet J Rare Dis 17 , 318 (2022). https://doi.org:10.1186/s13023-022-02479-3 Bellus, G. A. et al. Achondroplasia is defined by recurrent G380R mutations of FGFR3. Am J Hum Genet 56 , 368-373 (1995). Leiva-Gea, A. et al. Achondroplasia: Update on diagnosis, follow-up and treatment. An Pediatr (Engl Ed) 97 , 423.e421-423.e411 (2022). https://doi.org:10.1016/j.anpede.2022.10.004 Savarirayan, R. et al. International Consensus Statement on the diagnosis, multidisciplinary management and lifelong care of individuals with achondroplasia. Nat Rev Endocrinol 18 , 173-189 (2022). https://doi.org:10.1038/s41574-021-00595-x Barreda-Bonis, A. C. et al. Expert consensus for the management of patients with achondroplasia in treatment with vosoritide. An Pediatr (Engl Ed) 101 , 401-410 (2024). https://doi.org:10.1016/j.anpede.2024.09.012 Hoover-Fong, J., McGready, J., Schulze, K., Alade, A. Y. & Scott, C. I. A height-for-age growth reference for children with achondroplasia: Expanded applications and comparison with original reference data. Am J Med Genet A 173 , 1226-1230 (2017). https://doi.org:10.1002/ajmg.a.38150 Baujat, G., Legeai-Mallet, L., Finidori, G., Cormier-Daire, V. & Le Merrer, M. Achondroplasia. Best Pract Res Clin Rheumatol 22 , 3-18 (2008). https://doi.org:10.1016/j.berh.2007.12.008 Table 1 Table 1 is available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table1.TestiteminformationoftheSangergenessequencing.doc Cite Share Download PDF Status: Posted Version 1 posted 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. 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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-5868024","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":415815007,"identity":"f306df25-7e50-480d-8bf9-27e2f23a5205","order_by":0,"name":"Qing Zhou","email":"","orcid":"","institution":"First Affiliated Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Qing","middleName":"","lastName":"Zhou","suffix":""},{"id":415815008,"identity":"39cb1da5-f8b9-4f81-afad-534113448434","order_by":1,"name":"huaxiang Zhong","email":"","orcid":"","institution":"First Affiliated Hospital of Wenzhou 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2","display":"","copyAsset":false,"role":"figure","size":359393,"visible":true,"origin":"","legend":"\u003cp\u003eThe Results of ACMG family gene analysis\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-5868024/v1/109181ef8d3b39322f5c093f.png"},{"id":91776397,"identity":"f2a9792b-8c35-4b8d-8f0d-0558655067f0","added_by":"auto","created_at":"2025-09-20 19:46:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1230035,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5868024/v1/c11bad30-59ae-4ff7-b1e5-51f26229001d.pdf"},{"id":76582796,"identity":"12bf1969-ff09-4641-b40f-bdcaa182d4b1","added_by":"auto","created_at":"2025-02-18 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A short FL, defined as fetal FL below the 5th percentile or \u0026minus;\u0026thinsp;2 standard deviations (SD) for gestational age by ultrasound, marks aneuploidy or skeletal dysplasia\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Other concurrent abnormalities, such as macrocephaly, forehead protrusion, midface dysplasia, flat nose bridge, \"three-pronged hand,\" and excessive amniotic fluid, can also assist the diagnosis. It can be caused by physiological factors, such as heredity, normal small for gestational age infant (nSGA), and pathological factors, such as abnormal skeletal development system, fetal chromosome abnormality, and fetal growth restriction (FGR)\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAchondroplasia (ACH) is the most common non-lethal skeletal dysplasia in fetuses, with an incidence rate of 1.3\u0026thinsp;~\u0026thinsp;6.0 per 100,000 populations\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. It mainly affects the growth of long bones in fetal limbs after 25 weeks of gestation\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. ACH is primarily caused by fibroblast growth factor receptor 3 (FGFR3) gene mutation located on chromosome 4p16. 3\u003csup\u003e6,7\u003c/sup\u003e. Most patients present with C.1138G\u0026thinsp;\u0026gt;\u0026thinsp;A mutation, while a few show nucleotide C.1 138G\u0026thinsp;\u0026gt;\u0026thinsp;C mutation, leading to the encoded amino acid at position380 changing from glycine (Gly) to arginine (Arg)\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Therefore, the gold standard for ACH diagnosis is a mutation at 1138 nucleotides of the FGFR3 gene.\u003c/p\u003e \u003cp\u003eIn this study, a fetus with short FL caused by ACH was detected by routine ultrasonography during the 26th week of gestation in a 24-year-old woman who decided to continue the pregnancy and keep the baby. The fetus and her family were followed up for 2.5 years. A family-centered evaluation and follow-up schedule was established to analyze all B-ultrasound results, postnatal genetic test results, and early childhood growth and development. Our study would provide a reference and suggestions for family-oriented life-cycle management of fetal short FL caused by ACH.\u003c/p\u003e"},{"header":"Case report","content":"\u003cp\u003eA pregnant woman with the last menstruation on January 16, 2020, and an expected date of delivery on October 22, 2020, was detected with fetal short FL in the early pregnancy B-ultrasound on March 5, 2020. After being told the prognosis, the pregnant woman and her family decided to deliver the baby. The fetus and her family were followed up from 26 gestational weeks to May 2023.\u003c/p\u003e\n\u003cp\u003eAll clinical information of the pregnant women during the whole gestational period was collected, including blood tests, Down\u0026apos;s screening, non-invasive DNA, N-TB super loading, etc. The baby\u0026apos;s clinical information at birth was also collected, including Apgar score, height, weight, body surface deformity, head size and shape, mouth cleft lip and palate, neck symmetry, range of motion, and thorax shape. The ACH-specific growth parameter registry (height, body mass, head circumference) at birth and weeks 1, 2, 4, and 6 was used for longitudinal monitoring\u003csup\u003e\u003cspan\u003e8\u003c/span\u003e,\u003cspan\u003e9\u003c/span\u003e\u003c/sup\u003e. The baby was later followed up once a month from Month 2 to Month 12, then every two months till age 2.5 years, and every three months thereafter.\u003c/p\u003e\n\u003cp\u003eThe following measurement indexes of ultrasound screening were recorded: Ratio of FL to HC (FL/HC), ratio of FL to AC (FL/AC), Z-value of FL (ZFL), Z-value of HC (ZHC), Z-value of AC (ZAC), the subtraction between the ∆ZH-F\u0026thinsp;=\u0026thinsp;ZHC-ZFL, as ZAC and the difference between the ZFL and delta useful - F [useful\u0026thinsp;+\u0026thinsp;A - F\u0026thinsp;=\u0026thinsp;2 e = (ZHC - ZFL) + (ZAC - ZFL)\u0026thinsp;=\u0026thinsp;ZHC\u0026thinsp;+\u0026thinsp;ZAC \u0026minus;\u0026thinsp;2 ZFL]. Z-value = (measured value - standard value for the gestational age)/ standard deviation (SD). The standard values and SDs for the gestational age were based on Leung et al.\u0026apos;s fetal biometric standards of the Chinese population\u003csup\u003e\u003cspan\u003e10\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eFL/HC and FL/AC are indicators for fetal growth and development and can be used to predict adverse pregnancy outcomes. The normal values of FL/HC and FL/AC in fetuses from 22 to 34 weeks of gestation are 0.193\u0026ndash;0.207 and 0.199\u0026ndash;0.205, respectively\u003csup\u003e\u003cspan\u003e11\u003c/span\u003e\u003c/sup\u003e. FL/AC\u0026thinsp;\u0026lt;\u0026thinsp;0.160 is helpful in predicting fatal fetal bone dysplasia\u003csup\u003e\u003cspan\u003e9\u003c/span\u003e\u003c/sup\u003e. ZFL, ZHC, and ZAC represent the SD multiples of the difference between the fetal FL, HC, and AC values and the corresponding gestational week standard values. ZFL\u0026lt;-2.00 indicates a short femur, and ZHC\u0026thinsp;\u0026gt;\u0026thinsp;2.00 indicates a large head. ∆ZH-F indicates the SD multiple of femur development relative to head development. ∆ZH\u0026thinsp;+\u0026thinsp;A-2F indicates the SD multiple of femur development relative to head and abdominal development lag, with a higher value indicating a higher risk of genetic abnormalities in the fetus\u003csup\u003e\u003cspan\u003e12\u003c/span\u003e\u003c/sup\u003e .\u003c/p\u003e\n\u003cp\u003eSanger sequencing detected mutant genes in the sampled peripheral blood of the fetus (female) and its parents 7 months after birth (Table \u003cspan\u003e1\u003c/span\u003e). The sequencing data were analyzed by MutiationsSurveyor software developed by SoftGenetics Company. Children\u0026apos;s physical growth measurement tools, methods, and precautions were based on the recommendations proposed by the Group of Child Health Care, Society of Pediatrics, Chinese Medical Association\u003csup\u003e\u003cspan\u003e13\u003c/span\u003e,\u003cspan\u003e14\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eTable 2. Prenatal fetal ultrasound and index analysis results \u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"615\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eGW\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eBPD（mm）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eHC（mm）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eAC\u003c/p\u003e\n \u003cp\u003e(mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eFL\u003c/p\u003e\n \u003cp\u003e（mm）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eZ\u003csub\u003eBPD\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eZ\u003csub\u003eHC\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eZ\u003csub\u003eAC\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eZ\u003csub\u003eFL\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eFL/HC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eFL/AC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e∆Z\u003csub\u003eH-F\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e∆Z\u003csub\u003eH+A+2F\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e-12.20\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e-7.66\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e-5.55\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e-11.94\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0.15\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0.12\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e4.28\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e10.67\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e132\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e109\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e-20.40\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e-3.63\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e-7.13\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e-28.36\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0.15\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0.18\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e24.73\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e45.96\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e202\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e175\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e-21.44\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e-20.23\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e-12.28\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e-46.68\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0.17\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0.19\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e26.45\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e60.86\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e230\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e205\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e-18.71\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e-9.92\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e-10.30\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e-50.47\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0.16\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e40.55\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e80.73\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e254\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e228\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e39.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e-7.58\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e-4.32\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e-0.51\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e-62.74\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0.16\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0.17\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e58.42\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e120.64\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e277\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e-0.93\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e2.12\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0.96\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e-65.41\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0.16\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0.17\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e67.53\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e133.91\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e305\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e270\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e9.99\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e15.61\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e6.05\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e-79.19\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0.15\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0.17\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e94.80\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e180.04\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e316\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e278\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e14.98\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e18.56\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0.15\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e-81.96\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0.15\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0.17\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e100.52\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e182.62\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e334\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e326\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e14.24\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e15.05\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e21.37\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e-84.08\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0.15\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0.15\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e99.13\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e204.58\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e336\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e334\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e20.15\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e28.79\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e21.47\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e-85.02\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0.15\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0.15\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e113.81\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e220.30\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e347\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e356\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e22.30\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e7.82\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e26.69\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e-92.36\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0.14\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0.14\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e100.18\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e219.22\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 3. Basic physical development of the baby from birth to 24 months\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"559\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eInterval\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eweight(g)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eweight Median\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eLength\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(\u003cstrong\u003ecm\u003c/strong\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003elength Median\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003ehead circumference\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(\u003cstrong\u003ecm\u003c/strong\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003ehead circumference Median\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAt birth\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3540\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e35.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e1wks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3652\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\"\u003e\n \u003cp\u003e879\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"5\"\u003e\n \u003cp\u003e8.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e35.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"5\"\u003e\n \u003cp\u003e4.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e2wks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3790\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e48.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e36.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e3wks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4136\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e49.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e36.45\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e4wks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4480\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e50.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e36.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e1-2mo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4762\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e744\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e51.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e37.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e2-3 mo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5248\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e718\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e53.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e38.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.55\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e3-4 mo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e6102\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e585\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e54.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e39.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e4-5 mo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e6630\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e489\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e55.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e39.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e5-6 mo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7038\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e401\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e40.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.95\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e6-7 mo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7438\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e344\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e58\u003c/p\u003e\n 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\u003cp\u003e59.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e42.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e9- 10 mo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e8238\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e245\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e43.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e10- 11 mo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e8520\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n 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\u003cp\u003e9089\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e437\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e64.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e44.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e14-16mo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e9430\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e401\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e65.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e45.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e16-18mo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e9801\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e401\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e65.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e46.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e18-20mo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e10109\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e393\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e66.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e47.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e20-22mo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e10528\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e382\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e66.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e48.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e22-24mo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e10987\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e376\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e67 \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cdiv\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eAt 26 weeks of prenatal ultrasound screening, the pregnant woman was informed that the fetus had short limbs. The femur length was 50.47 SD lower than the normal value, the biparietal diameter was 18.71 SD lower than the normal value, FL/HC was 0.16, lower than the normal value (0.193\u0026ndash;0.207), and FL/AC was 0.17. All B-ultrasound results during pregnancy were collected. Specific data are shown in Table \u003cspan\u003e2\u003c/span\u003e \u0026amp; Fig. \u003cspan\u003e1\u003c/span\u003e.\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eSequencing analysis of disease-related genes identified highly suspicious variants associated with the disease phenotype. A heterozygous mutation in the FCFR3 gene was found. c.1138G\u0026thinsp;\u0026gt;\u0026thinsp;A (p.G380R), and there was no variation in this site in either parent of the baby. The specific variation is unknown in the heterozygous mutation of nucleotide 1138 from guanine G to adenine A (c.1138G\u0026thinsp;\u0026gt;\u0026thinsp;A), resulting in amino acid 380 from glycine to arginine (p.G380R). The results of the ACMG family gene analysis are shown in Fig. \u003cspan\u003e2\u003c/span\u003e.\u003c/p\u003e\n\u003cp\u003eThe medical team monitored the baby\u0026apos;s general development, including the height, weight, and head circumference, from birth to 24 months of age, according to the 2009 WHO Child Growth Standards (2009 WHO). The results are shown in Table \u003cspan\u003e3\u003c/span\u003e.\u003c/p\u003e\n\u003cdiv\u003e\n\u003c/div\u003e\n\u003cdiv\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe diagnosis of short FL is mainly based on B-ultrasound, which is a routine prenatal examination for the initial diagnosis of fetal femur microsomia. However, B-ultrasound can only diagnose short FL after 26 weeks of gestation since the fetal skeletal system has not yet fully formed during early pregnancy. Before the molecular diagnosis of ACH became a routine clinical program, ultrasound still maintained the primary method for prenatal diagnosis of ACH\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. In this study, the fetus had short FL at 12 weeks of gestation, which was about 11 SD lower than the normal standard. ZHC\u0026thinsp;\u0026gt;\u0026thinsp;6 after 32 weeks, indicating a large head circumference. ∆ZH-F was 4.28-100.18 SD multiples, suggesting that femur development lagged severely behind head development. The values of ∆ZH\u0026thinsp;+\u0026thinsp;A-2F were in the range of 10.67-219.22 SD multiples, which also revealed that the femur development lagged severely behind the head and abdomen, suggesting a high risk of genetic abnormalities in the fetus.\u003c/p\u003e \u003cp\u003eACH is caused by mutations in FGFR3 (4p16.3), a gene encoded by fibroblast growth factor receptor-3 (FGFR3). 98% of ACH patients carry the FGFR3c.1138G\u0026thinsp;\u0026gt;\u0026thinsp;A mutation, and 1% carry the FGFR3 C.1138G\u0026thinsp;\u0026gt;\u0026thinsp;C mutation, both can cause glycine replacement to arginine (G380R) in the 380th transmembrane region of FGFR3\u003csup\u003e16\u003c/sup\u003e. The case in this study is consistent with those reported in the literature. Studies have shown that ACH is an autosomal dominant genetic disease with 100% penetrance, which can cause death in the early embryo or at birth or within 1 year after birth due to severe chondroid developmental disorder. This case was non-fatal ACH, and the child had grown to 30 months by June 2023. No case of a \"three-pronged hand\" was found, but the child had a short root form of limbs, which was consistent with the literature\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eMost ACH mutations are heterozygous, and 80% of them are sporadic cases with normal parental phenotypes, which is also the case in this study. Both parents of the patient showed normal phenotypes, and there were no ACH cases in the three generations of the child's ancestors, suggesting a sporadic ACH. Most of the pathogenic genes of ACH come from the father and show a typical paternal age effect. The risk of ACH increases by 5.0 times when the paternal age is \u0026ge;\u0026thinsp;40 years and by 10 times when the paternal age is over 50 years old\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. In this case, the patient's father was exactly 40 years old when she was born, which may indicate the paternal age effect. The patient's mom did not have any disease or receive any drug treatment during the first three months of pregnancy. All prenatal blood tests at 6 weeks of pregnancy were normal except for a history of rubella virus infection, which presented no symptoms and required no further treatment. On May 7, 2020, the mom underwent Down's screening, non-invasive DNA, and N-TB ultrasounds, all indicated no abnormalities, further proving that ACH was caused by heterozygous mutations.\u003c/p\u003e \u003cp\u003eThe Apgar score of the patient at birth was 10, which basically ruled out fatal dwarfism and other skeletal problems. At birth, she was 46cm in height and 3540g in weight, with no deformity or abnormality. The patient's height was close to the percentile value P10 (51.6) in the first month after birth and was lower than the standard in the next 24 months. According to the recommendations of the Child Health Group of the Pediatrics Society of the Chinese Medical Association, the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;2S or the 3\u0026ndash;97 percentile (P) is considered the normal range. The 24-month head circumference was located between P90 and P97 (49.8), which means a significant larger size of the head, and the limbs were shorter than normal. In this period, the teamwork aimed at helping the family to accept the reality and embrace the baby as she is. According to the Bowen family system, a emotional fusion and differentiation\u003c/p\u003e \u003cp\u003eunderscores the significance of emotional supports in relationships.\u003c/p\u003e \u003cp\u003eThe body mass index for age (BMI/ age) at the 24th month was calculated to be 24.48, exceeding 3SD (20.4), and the family was reminded to strictly control the child's weight and reduce the intake of high-calorie food. In addition, a skull and thoracolumbar MR plan was developed to monitor the progressing of hydrocephalus and thoracolumbar compression in child.\u003c/p\u003e \u003cp\u003eThe study applied the theory of the Bowen family system, which viewed the family as an emotional unit and used system thinking to describe its complex interactions\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e No mental abnormalities were observed in the patient from birth to 2.5 years of age, which was consistent with the main symptoms of ACH described by Marie\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. During this period, the patient's family has been looking for appropriate treatment plans. According to the family's willingness, Chinese medicine therapy would be considered for future treatment. In this regard, the life cycle management of family-oriented practice services will be continued in this study to serve the family.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Ethics Committee of the First Affiliated Hospital of Wenzhou Medical University（KY2023-R187）\u003c/p\u003e\n\u003cp\u003eBefore initiating the study, the researchers engaged in communication with the participant\u0026apos;s mother. Detailed information was provided, \u0026nbsp;including its objectives, the methods that would be employed, and the potential risks and benefits involved. The researchers then obtained written consent from her mother, which served as a formal record of the participant\u0026apos;s agreement to take part in the study. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe consent for publication had been obtained from the mother.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Availability of data and materials\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003eCompeting interests:\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Funding: Not applicable\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eD\u0026apos;Ambrosio, V.\u003cem\u003e et al.\u003c/em\u003e Midtrimester isolated short femur and perinatal outcomes: A systematic review and meta-analysis. \u003cem\u003eActa Obstet Gynecol Scand\u003c/em\u003e \u003cstrong\u003e98\u003c/strong\u003e, 11-17 (2019). https://doi.org:10.1111/aogs.13470\u003c/li\u003e\n\u003cli\u003ePapageorghiou, A. T., Fratelli, N., Leslie, K., Bhide, A. \u0026amp; Thilaganathan, B. Outcome of fetuses with antenatally diagnosed short femur. \u003cem\u003eUltrasound Obstet Gynecol\u003c/em\u003e \u003cstrong\u003e31\u003c/strong\u003e, 507-511 (2008). https://doi.org:10.1002/uog.5265\u003c/li\u003e\n\u003cli\u003eNeumeyer, L., Merker, A. \u0026amp; Hagen\u0026auml;s, L. Clinical charts for surveillance of growth and body proportion development in achondroplasia and examples of their use. \u003cem\u003eAm J Med Genet A\u003c/em\u003e \u003cstrong\u003e185\u003c/strong\u003e, 401-412 (2021). https://doi.org:10.1002/ajmg.a.61974\u003c/li\u003e\n\u003cli\u003eChitty, L. S.\u003cem\u003e et al.\u003c/em\u003e New aids for the non-invasive prenatal diagnosis of achondroplasia: dysmorphic features, charts of fetal size and molecular confirmation using cell-free fetal DNA in maternal plasma. \u003cem\u003eUltrasound Obstet Gynecol\u003c/em\u003e \u003cstrong\u003e37\u003c/strong\u003e, 283-289 (2011). https://doi.org:10.1002/uog.8893\u003c/li\u003e\n\u003cli\u003eMerker, A.\u003cem\u003e et al.\u003c/em\u003e Development of body proportions in achondroplasia: Sitting height, leg length, arm span, and foot length. \u003cem\u003eAm J Med Genet A\u003c/em\u003e \u003cstrong\u003e176\u003c/strong\u003e, 1819-1829 (2018). https://doi.org:10.1002/ajmg.a.40356\u003c/li\u003e\n\u003cli\u003eStoll, C., Dott, B., Roth, M. P. \u0026amp; Alembik, Y. Birth prevalence rates of skeletal dysplasias. \u003cem\u003eClin Genet\u003c/em\u003e \u003cstrong\u003e35\u003c/strong\u003e, 88-92 (1989). https://doi.org:10.1111/j.1399-0004.1989.tb02912.x\u003c/li\u003e\n\u003cli\u003eTofts, L., Das, S., Collins, F. \u0026amp; Burton, K. L. O. Growth charts for Australian children with achondroplasia. \u003cem\u003eAm J Med Genet A\u003c/em\u003e \u003cstrong\u003e173\u003c/strong\u003e, 2189-2200 (2017). https://doi.org:10.1002/ajmg.a.38312\u003c/li\u003e\n\u003cli\u003eHoover-Fong, J., Scott, C. I. \u0026amp; Jones, M. C. Health Supervision for People With Achondroplasia. \u003cem\u003ePediatrics\u003c/em\u003e \u003cstrong\u003e145\u003c/strong\u003e (2020). https://doi.org:10.1542/peds.2020-1010\u003c/li\u003e\n\u003cli\u003eRahemtullah, A., McGillivray, B. \u0026amp; Wilson, R. D. Suspected skeletal dysplasias: femur length to abdominal circumference ratio can be used in ultrasonographic prediction of fetal outcome. \u003cem\u003eAm J Obstet Gynecol\u003c/em\u003e \u003cstrong\u003e177\u003c/strong\u003e, 864-869 (1997). https://doi.org:10.1016/s0002-9378(97)70284-9\u003c/li\u003e\n\u003cli\u003eHadlock, F. P., Harrist, R. B., Shah, Y. \u0026amp; Park, S. K. The femur length/head circumference relation in obstetric sonography. \u003cem\u003eJ Ultrasound Med\u003c/em\u003e \u003cstrong\u003e3\u003c/strong\u003e, 439-442 (1984). https://doi.org:10.7863/jum.1984.3.10.439\u003c/li\u003e\n\u003cli\u003eHerrera, C. L., Hussamy, D. J., McIntire, D. D., Twickler, D. M. \u0026amp; Dashe, J. S. Femur length parameters in fetuses with Down syndrome\u0026dagger;. \u003cem\u003eJ Matern Fetal Neonatal Med\u003c/em\u003e \u003cstrong\u003e33\u003c/strong\u003e, 2516-2521 (2020). https://doi.org:10.1080/14767058.2018.1554047\u003c/li\u003e\n\u003cli\u003eCrane, H. M.\u003cem\u003e et al.\u003c/em\u003e The Reliability of Ultrasound Markers in Identifying Fetuses With a Life-Limiting Skeletal Dysplasia. \u003cem\u003ePrenat Diagn\u003c/em\u003e \u003cstrong\u003e44\u003c/strong\u003e, 1318-1326 (2024). https://doi.org:10.1002/pd.6638\u003c/li\u003e\n\u003cli\u003e[Expert consensus on clinical practice of assessment and management of childhood physical development]. \u003cem\u003eZhonghua Er Ke Za Zhi\u003c/em\u003e \u003cstrong\u003e59\u003c/strong\u003e, 169-174 (2021). https://doi.org:10.3760/cma.j.cn112140-20210116-00050\u003c/li\u003e\n\u003cli\u003eYH., Z. Analysis of causes and nursing intervention measures of accidental tube withdrawal in patients with external thoracic surgery. \u003cem\u003eChinese Remedies \u0026amp; Clinics\u003c/em\u003e \u003cstrong\u003e21\u003c/strong\u003e, 1041-1043 (2021). https://doi.org:DOI:10.11655/zgywylc2021.06.068\u003c/li\u003e\n\u003cli\u003eFredwall, S.\u003cem\u003e et al.\u003c/em\u003e Optimising care and follow-up of adults with achondroplasia. \u003cem\u003eOrphanet J Rare Dis\u003c/em\u003e \u003cstrong\u003e17\u003c/strong\u003e, 318 (2022). https://doi.org:10.1186/s13023-022-02479-3\u003c/li\u003e\n\u003cli\u003eBellus, G. A.\u003cem\u003e et al.\u003c/em\u003e Achondroplasia is defined by recurrent G380R mutations of FGFR3. \u003cem\u003eAm J Hum Genet\u003c/em\u003e \u003cstrong\u003e56\u003c/strong\u003e, 368-373 (1995).\u003c/li\u003e\n\u003cli\u003eLeiva-Gea, A.\u003cem\u003e et al.\u003c/em\u003e Achondroplasia: Update on diagnosis, follow-up and treatment. \u003cem\u003eAn Pediatr (Engl Ed)\u003c/em\u003e \u003cstrong\u003e97\u003c/strong\u003e, 423.e421-423.e411 (2022). https://doi.org:10.1016/j.anpede.2022.10.004\u003c/li\u003e\n\u003cli\u003eSavarirayan, R.\u003cem\u003e et al.\u003c/em\u003e International Consensus Statement on the diagnosis, multidisciplinary management and lifelong care of individuals with achondroplasia. \u003cem\u003eNat Rev Endocrinol\u003c/em\u003e \u003cstrong\u003e18\u003c/strong\u003e, 173-189 (2022). https://doi.org:10.1038/s41574-021-00595-x\u003c/li\u003e\n\u003cli\u003eBarreda-Bonis, A. C.\u003cem\u003e et al.\u003c/em\u003e Expert consensus for the management of patients with achondroplasia in treatment with vosoritide. \u003cem\u003eAn Pediatr (Engl Ed)\u003c/em\u003e \u003cstrong\u003e101\u003c/strong\u003e, 401-410 (2024). https://doi.org:10.1016/j.anpede.2024.09.012\u003c/li\u003e\n\u003cli\u003eHoover-Fong, J., McGready, J., Schulze, K., Alade, A. Y. \u0026amp; Scott, C. I. A height-for-age growth reference for children with achondroplasia: Expanded applications and comparison with original reference data. \u003cem\u003eAm J Med Genet A\u003c/em\u003e \u003cstrong\u003e173\u003c/strong\u003e, 1226-1230 (2017). https://doi.org:10.1002/ajmg.a.38150\u003c/li\u003e\n\u003cli\u003eBaujat, G., Legeai-Mallet, L., Finidori, G., Cormier-Daire, V. \u0026amp; Le Merrer, M. Achondroplasia. \u003cem\u003eBest Pract Res Clin Rheumatol\u003c/em\u003e \u003cstrong\u003e22\u003c/strong\u003e, 3-18 (2008). https://doi.org:10.1016/j.berh.2007.12.008\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table 1","content":"\u003cp\u003eTable 1 is available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"achondroplasia, life-cycle management, short femur length, short limbs","lastPublishedDoi":"10.21203/rs.3.rs-5868024/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5868024/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAchondroplasia (ACH) is the most common non-lethal skeletal dysplasia and can lead to short femur length (FL), which is uncommon in the pediatric setting. This case report describes a case of fetal short FL caused by ACH, which was detected by routine ultrasonography during the 26th week of gestation in a 24-year-old woman. Based on the theory of the Bowen family system, the study followed the fetus and her family for 2.5 years, observed and analyzed the growth and development of the fetus, and provided psychological support to the family. In cases like this, life-cycle management is crucial and beneficial to ensure the healthy development and growth of the fetus with short femur length in the long term.\u003c/p\u003e","manuscriptTitle":"Life-cycle management of fetal short femur length caused by achondroplasia: A case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-02-18 15:01:52","doi":"10.21203/rs.3.rs-5868024/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"851ebfee-74bc-419e-8c96-d3a1982e98b9","owner":[],"postedDate":"February 18th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-09-20T19:38:24+00:00","versionOfRecord":[],"versionCreatedAt":"2025-02-18 15:01:52","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5868024","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5868024","identity":"rs-5868024","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}