Prenatal Sonographic Features and Genotype–Phenotype Correlations in Coffin–Siris Syndrome: A Systematic Case Analysis of 32 Fetuses

Prenatal Sonographic Features and Genotype–Phenotype Correlations in Coffin–Siris Syndrome: A Systematic Case Analysis of 32 Fetuses | 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 Prenatal Sonographic Features and Genotype–Phenotype Correlations in Coffin–Siris Syndrome: A Systematic Case Analysis of 32 Fetuses Qiao Zhou, Chunli Jing This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9085595/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Background Coffin–Siris syndrome (CSS) is a rare multisystem genetic disorder caused by pathogenic variants in genes encoding components of the BAF/SWI–SNF chromatin-remodeling complex. Prenatal recognition is difficult because the phenotypic spectrum is heterogeneous and many characteristic features emerge only after birth. We aimed to summarize the prenatal imaging spectrum of CSS and explore potential genotype–phenotype associations. Methods A systematic review of PubMed, Embase, and Scopus was performed to identify reported cases of prenatally diagnosed CSS with documented fetal imaging findings. Cases published between 2016 and 2025 with molecular confirmation and detailed prenatal ultrasound data were included. Clinical characteristics, genetic variants, prenatal imaging findings, and pregnancy outcomes were extracted and analyzed descriptively. Results Thirty-two fetuses with genetically confirmed CSS were included. Structural abnormalities were most frequently identified in the central nervous system (18/32, 56.3%), particularly ventriculomegaly, corpus callosum abnormalities, and posterior fossa malformations. Congenital heart defects were present in 8 cases (25.0%). Other recurrent findings included intrauterine growth restriction, abnormal amniotic fluid volume, diaphragmatic hernia, and limb anomalies. Multisystem involvement (≥ 2 organ systems) was observed in 24 fetuses (75.0%). Variants in ARID1A were associated with the highest frequency of prenatal central nervous system abnormalities (78.6%). Despite these structural findings, typical postnatal features of CSS, including craniofacial dysmorphism and fifth-digit or nail hypoplasia, were rarely detectable prenatally. Conclusions Coffin–Siris syndrome may present during fetal life with a pattern of multisystem structural anomalies, most commonly involving the central nervous and cardiovascular systems. However, hallmark craniofacial and distal limb features are often not apparent on prenatal imaging. Recognition of combined structural abnormalities should prompt consideration of CSS and may support early genomic testing and prenatal counseling. Coffin–Siris syndrome prenatal diagnosis ultrasound genotype-phenotype correlation pregnancy outcome Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Coffin–Siris syndrome (CSS) is a rare genetic disorder characterized primarily by neurodevelopmental delay, typically accompanied by hypoplasia or aplasia of the fifth fingernail or toenail, distinctive facial features, hypertrichosis, and variable congenital anomalies. The syndrome was first described in 1970 by Coffin and Siris in patients presenting with intellectual disability and absent or underdeveloped fifth distal phalanges and nails [ 1 ]. Beyond its characteristic limb and facial manifestations, CSS is frequently associated with multisystem involvement. Reported anomalies include congenital heart defects, diaphragmatic hernia, and other structural malformations [ 2 ], as well as visual and hearing impairments, epilepsy, and severe cognitive dysfunction [ 3 ]. Most affected individuals exhibit moderate to profound developmental delay and require long-term medical, rehabilitative, and social support, resulting in a substantial burden on families and healthcare systems [ 2 ]. Overall, the prognosis of CSS is considered unfavorable, particularly in cases with early-onset seizures or major structural anomalies. Despite its clinical significance, prenatal identification of CSS remains challenging. The phenotypic spectrum is highly heterogeneous, and many hallmark features evolve progressively during gestation or become apparent only after birth [ 4 ]. Existing literature has focused largely on postnatal clinical phenotypes and molecular findings, whereas systematic descriptions of prenatal ultrasound manifestations are scarce. Consequently, many cases are diagnosed only in the postnatal period, limiting opportunities for timely prenatal counseling and informed decision-making. In this context, a comprehensive characterization of prenatal ultrasound features associated with Coffin–Siris syndrome, particularly in relation to different genetic subtypes, is of considerable clinical importance. The present study aims to systematically review reported cases to delineate the prenatal sonographic spectrum of CSS and explore genotype–phenotype correlations, thereby providing imaging-based evidence to support improved prenatal recognition and counseling. Methods Study design This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. As the study was based exclusively on previously published data, ethical approval was not required. Search strategy A comprehensive literature search was performed in PubMed, Embase, and Scopus from database inception to September 1, 2025. The search strategy combined controlled vocabulary (MeSH and Emtree terms) and free-text keywords related to Coffin–Siris syndrome and prenatal imaging. The following terms were used in various combinations: Coffin–Siris syndrome,” “CSS,” “BAF complex,” “SWI/SNF,” “prenatal diagnosis,” “prenatal ultrasound,” “fetal imaging,” “fetal MRI,” “prenatal screening,” and “congenital anomalies. The search was restricted to studies published in English. Reference lists of included articles were manually screened to identify additional relevant reports. Eligibility criteria Studies were included if they met the following criteria: Reported fetuses with genetically confirmed Coffin–Siris syndrome; Provided documented prenatal imaging findings (ultrasound and/or fetal MRI); Presented sufficient clinical and genetic information for data extraction. Studies were excluded if: Prenatal imaging findings were not described; Genetic confirmation was unavailable; Data were incomplete or duplicated in other reports. Study selection After removal of duplicates, two reviewers independently screened titles and abstracts for eligibility. Full texts of potentially relevant articles were assessed independently. Disagreements were resolved through discussion and consensus. The selection process is illustrated in Fig. 1 . Publication bias was not formally assessed due to the nature of case reports/series, but the potential impact of selective reporting is addressed in the limitations. Data extraction Data were extracted independently by two investigators using a standardized data collection form. Extracted variables included: Maternal age, Gestational age at diagnosis, Fetal sex, Gene variant and inheritance pattern, Prenatal imaging findings by organ system, Pregnancy outcome, Postnatal clinical features. Quality assessment Given that most included studies were case reports or case series, methodological quality was assessed using an adapted version of the CARE (Case Report) checklist to evaluate completeness of reporting. Formal assessment of the certainty of evidence was not performed, as all included studies were case reports or small case series without comparators. However, the diagnostic certainty of CSS in this cohort is high, as all cases had molecular confirmation. Statistical analysis Descriptive statistical analysis was performed using SPSS version 26.0 (IBM Corp., Armonk, NY, USA). Continuous variables were expressed as ranges or medians when appropriate. Categorical variables were summarized as frequencies and percentages. Python (version 3.9; Python Software Foundation, Wilmington, DE, USA) was used for additional data organization and visualization. To explore potential sources of heterogeneity in prenatal phenotypes, we performed descriptive subgroup analyses based on the affected gene. Findings were compared across gene subgroups to identify patterns of organ system involvement, although no formal statistical testing was conducted due to small sample sizes in certain genotype groups. Results Study characteristics and genetic findings A total of 32 prenatally diagnosed cases were included, with the distribution of pathogenic variants, inheritance patterns, and pregnancy outcomes summarized in Table 1 , stratified by gene. These cases were drawn from publications between 2016 and 2025. Maternal age ranged from 19 to 38 years, and most pregnancies were sporadic, with de novo pathogenic variants identified in the majority of cases. Among the cases where fetal sex was reported, the male-to-female ratio was 1.07:1. Pathogenic or likely pathogenic variants were identified in genes encoding components of the BAF/SWI–SNF chromatin-remodeling complex or related regulatory genes, including ARID1A representing the largest subgroup (n = 14), followed by SMARCA4 (n = 4), SMARCB1 (n = 3), ARID1B (n = 3), SMARCC2 (n = 1), SMARCD1 (n = 1), ARID2 (n = 1), SMARCA2 (n = 1), SMARCE1 (n = 3), and SOX11(n = 1). Table 1 Study characteristics, variant types, inheritance patterns, and pregnancy outcomes stratified by gene (n = 32). Category Total n/N (%) ARID1A (n = 14) ARID1B (n = 3) ARID2 (n = 1) SMARCA2 (n = 1) SMARCA4 (n = 4) SMARCB1 (n = 3) SMARCC2 (n = 1) SMARCD1 (n = 1) SMARCE1 (n = 3) SOX11 (n = 1) Sex Female 14 (43.8) 6 (42.9) 2 (66.7) 0 (0%) 1 (100.0) 1 (25.0) 2 (66.7) 0 (0.0) 0 (0.0) 2 (66.7) 0 (0.0) Male 15 (46.9) 7 (50.0) 1 (33.3) 1 (100%) 0 (0.0) 2 (50.0) 1 (33.3) 0 (0.0) 1 (100.0) 1 (33.3) 1 (100.0) Not evaluated 3 (9.4) 1 (7.1) 0 (0.0) 0 (0.0) 0 (0.0) 1 (25.0) 0 (0.0) 1 (100.0) 0 (0.0) 0 (0.0) 0 (0.0) Variant type LOF 17 (53.1) 11 (78.6) 3 (100.0) 1 (100.0) 0 (0.0) 0 (0.0) 1 (33.3) 1 (100.0) 0 (0.0) 0 (0.0) 0 (0.0) Missense 14 (43.8) 3 (21.4) 0 (0.0) 0 (0.0) 0 (0.0) 4 (100.0) 2 (66.7) 0 (0.0) 1 (100.0) 3 (100.0) 1 (100.0) Other 1 (3.1) 0 (0.0) 0 (0.0) 0 (0.0) 1 (100.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Inheritance De novo 29 (90.6) 13 (92.9) 2 (66.7) 1 (100.0) 0 (0.0) 4 (100.0) 3 (100.0) 1 (100.0) 1 (100.0) 3 (100.0) 1 (100.0) Inherited 3 (9.4) 1 (7.1) 1 (33.3) 0 (0.0) 1 (100.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Pregnancy outcome Live birth 18 (56.3) 6 (42.9) 3 (100.0) 0 (0.0) 1 (100.0) 3 (75.0) 2 (66.7) 0 (0.0) 0 (0.0) 2 (66.7) 1 (100.0) TOP 12 (37.5) 7 (50.0) 0 (0.0) 1 (100.0) 0 (0.0) 1 (25.0) 1 (33.3) 1 (100.0) 0 (0.0) 1 (33.3) 0 (0.0) IUFD 2 (6.3) 1 (7.1) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (100.0) 0 (0.0) 0 (0.0) LOF, loss-of-function variants including nonsense, frameshift, and canonical splice-site variants; Other variant types include in-frame variants or complex rearrangements; TOP, termination of pregnancy; IUFD, intrauterine fetal death. Percentages are calculated within each gene column. Among these, ARID1A-related variants were the most frequently reported, accounting for nearly half of the cases, followed by SMARCA4 and SMARCB1. Most variants were loss-of-function mutations, including frameshift, nonsense, or splice-site variants, consistent with haploinsufficiency. Inheritance information was available for most cases, revealing that 90.6% of variants were de novo, with only a few inherited cases, often associated with milder prenatal phenotype. Prenatal ultrasonographic findings Prenatal structural abnormalities were observed across multiple organ systems (Table 2 ). Prenatal ultrasound abnormalities were detected as early as the first trimester, with gestational age at diagnosis ranging from 12 to 32 weeks. Central nervous system (CNS) abnormalities constituted the most frequent prenatal findings, observed in 18 of 32 cases (56.3%). The predominant CNS anomalies were ventriculomegaly or hydrocephalus, affecting 13 individuals (40.6%), and abnormalities of the corpus callosum, present in 7 cases (21.9%). Posterior fossa abnormalities (3 cases, 9.4%), cerebellar anomalies (4 cases, 12.5%), and encephalocele (1 case, 3.1%) were also observed. ARID1A demonstrated the highest frequency, with CNS involvement identified in 11 of 14 cases (78.6%) (Fig. 2 ). Despite the limited number of reported cases, the incidence among other phenotypic associations is below 35%. Table 2 Prenatal imaging findings stratified by organ system and gene (n = 32). Organ system Total n/N (%) ARID1A (n = 14) ARID1B (n = 3) ARID2 (n = 1) SMARCA2 (n = 1) SMARCA4 (n = 4) SMARCB1 (n = 3) SMARCC2 (n = 1) SMARCD1 (n = 1) SMARCE1 (n = 3) SOX11 (n = 1) CNS anomalies Ventriculomegaly 13 (40.6) 10 (71.4) 1 (33.3) 0 (0.0) 0 (0.0) 0 (0.0) 2 (66.7) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Corpus callosum anomaly 6 (18.8) 3 (21.4) 0 (0.0) 0 (0.0) 0 (0.0) 1 (25.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (33.3) 1 (100.0) Posterior fossa anomaly 3 (9.4) 2 (14.3) 1 (33.3) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Cerebellar anomaly 4 (12.5) 2 (14.3) 1 (33.3) 0 (0.0) 0 (0.0) 1 (25.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Encephalocele 1 (3.1) 1 (7.1) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Other CNS 2 (6.3) 1 (7.1) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (33.3) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) CVS anomalies Conotruncal defect 2 (6.3) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100.0) 0 (0.0) 0 (0.0) 0 (0.0) AVSD 3 (9.4) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (25.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (66.7) 0 (0.0) Septal defect 2 (6.3) 2 (14.3) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Other CVS 2 (6.3) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (25.0) 1 (33.3) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Other systems IUGR 6 (18.8) 0 (0.0) 1 (33.3) 0 (0.0) 1 (100.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (100.0) 2 (66.7) 1 (100.0) Polyhydramnios 5 (15.6) 3 (21.4) 0 (0.0) 0 (0.0) 0 (0.0) 1 (25.0) 1 (33.3) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Oligohydramnios 1 (3.1) 1 (7.1) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) CDH 4 (12.5) 2 (14.3) 0 (0.0) 1 (100.0) 0 (0.0) 1 (25.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Limb anomaly 4 (12.5) 2 (14.3) 1 (33.3) 0 (0.0) 0 (0.0) 0 (0.0) 1 (33.3) 0 (0.0) 0 (0.0) 0 (0.0) 1 (100.0) Increased NT 2 (6.3) 1 (7.1) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (33.3) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Renal anomaly 1 (3.1) 1 (7.1) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Single umbilical artery 3 (9.4) 2 (14.3) 0 (0.0) 0 (0.0) 0 (0.0) 1 (25.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Omphalocele 1 (3.1) 1 (7.1) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Lymphangioma 1 (3.1) 1 (7.1) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Categories are not mutually exclusive. n/N (%) indicates number of affected cases per total cases within each gene group. Categories are not mutually exclusive; some fetuses presented with multiple anomalies. CNS, central nervous system; CVS, cardiovascular system; AVSD, atrioventricular septal defect; CDH, congenital diaphragmatic hernia; IUGR, intrauterine growth restriction; NT, nuchal translucency. Cardiovascular system (CVS) abnormalities were identified prenatally in 8 of 32 cases (25.0%). The spectrum included conotruncal defects, such as tetralogy of Fallot and functional single ventricle (2 cases, 6.3%); atrioventricular septal defects (3 cases, 9.4%); and other septal defects (2 cases, 6.3%). One case had a right ventricular dimension at the upper limit of normal (1 cases, 3.1%). SMARCE1 showed the highest proportional involvement, with cardiac defects reported in 66.7% of cases. Cardiac involvement was less frequently reported in other genotypes. Beyond CNS and CVS anomalies, the most common were intrauterine growth restriction (IUGR, 6 cases, 18.9%) and abnormalities of amniotic fluid volume (5 cases, 15.6%), comprising both polyhydramnios (5 cases, 15.6%) and oligohydramnios (1 case, 3.1%). Structural anomalies included congenital diaphragmatic hernia (4 cases, 12.5%), limb abnormalities (4 cases, 12.5%), and increased nuchal translucency (≥ 3.0 mm, 2 cases, 6.3%). Placental or umbilical cord abnormalities were noted in 5 cases (15.6%) (Fig. 3 ). Most genotypes were associated with two or more abnormalities (24/32, 75%). Pregnancy outcomes and postnatal findings Adverse pregnancy outcomes were common. Termination of pregnancy (TOP) or stillbirth were performed in 14 of 32 cases (43.8%), most frequently prompted by severe central nervous system malformations, complex cardiovascu lar defects, or multisystem anomalies identified on prenatal imaging. Intrauterine fetal demise occurred in two cases (6.3%), while 18 pregnancies (56.3%) resulted in live birth (Table 3 , Fig. 4 ). Table 3 Postnatal phenotypic features in live-born cases stratified by gene (n = 18). Phenotype Total n/N (%) ARID1A (n = 6) ARID1B (n = 3) SMARCA2 (n = 1) SMARCA4 (n = 3) SMARCB1 (n = 2) SMARCE1 (n = 2) SOX11 (n = 1) Neurodevelopmental disorder 16 (88.9) 4 (66.7) 3 (100.0) 1 (100.0) 3 (100.0) 2 (100.0) 2 (100.0) 1(100.0) Hypotonia 6 (33.3) 2 (33.3) 2 (66.7) 0 (0.0) 1 (33.3) 1 (50.0) 0 (0.0) 0 (0.0) Seizure 2 (11.1) 1 (16.7) 0 (0.0) 0 (0.0) 1 (33.3) 0 (0.0) 0 (0.0) 0 (0.0) Nail anomaly 7 (38.9) 2 (33.3) 1 (33.3) 1 (100.0) 1 (33.3) 0 (0.0) 2 (100.0) 0 (0.0) Facial dysmorphism 17 (94.4) 6 (100.0) 3 (100.0) 1 (100.0) 3 (100.0) 1 (50.0) 2 (100.0) 1 (100.0) Ophthalmologic abnormalities 7 (38.9) 3 (50.0) 1 (33.3) 0 (0.0) 1 (33.3) 2 (100.0) 0 (0.0) 0 (0.0) Hearing loss 5 (27.8) 0 (0.0) 0 (0.0) 0 (0.0) 3 (100.0) 1 (50.0) 1 (50.0) 0 (0.0) Percentages are calculated within each gene column. Only live-born cases with available postnatal follow-up data were included. There were two cases without neurodevelopmental assessment. Neurodevelopmental disorder includes global developmental delay, intellectual disability, or autism spectrum disorder. Among the live-born infants, gestational age at delivery ranged from 30 to 40 weeks. A marked discrepancy between prenatal detection and postnatal diagnosis was observed (Table 4 ). While CNS structural anomalies were identified prenatally in 8 of 18 live-born cases (44.4%), postnatal evaluation revealed abnormalities in 11 cases (61.1%). Despite being rarely detectable prenatally, characteristic facial dysmorphism was identified in all live-born and stillborn cases, save for nine individuals lacking postnatal or post-mortem records. Table 4 Comparison of prenatal detection and postnatal manifestation of major phenotypic abnormalities (live-born cohort, n = 18). Abnormality Category Prenatal (All cases, n = 32) (n %) Prenatal (Live-born, n = 18) (n %) Postnatal (Live-born, n = 18) (n %) CNS structural anomalies 18 (56.3) 8 (44.4) 11 (61.1) CVS anomalies 8 (25.0) 4 (22.2) 9 (50.0) Limb/nail anomalies 4 (12.5) 2 (11.1) 13 (70.6) Facial dysmorphism 0 (0.0) 0 (0.0) 17 (94.4) CDH 4 (12.5) 3 (17.6) 5 (27.8) Some cases had multiple cardiac anomalies. Prenatal (All cases) refers to all 32 fetuses. Prenatal (Live-born) refers only to the 18 live-born cases. There was one case without reported facial findings. Postnatal data were available only for live-born cases. Categories are not mutually exclusive. CNS, central nervous system; CVS, cardiovascular system; CDH, congenital diaphragmatic hernia. Among the 18 live-born infants, one died on postnatal day 3 and one had not undergone evaluation at the time of reporting; of the remaining cases, 16 were found to have neurodevelopmental abnormalities, including global developmental delay, intellectual disability, hypotonia, and seizures. Limb and nail anomalies were frequently observed (17 cases, 94.4%), particularly involving the fifth digits. In addition, multisystem involvement was common, affecting the cardiovascular, gastrointestinal, genitourinary, and respiratory systems. Ophthalmological abnormalities were identified in 7 of the 18 evaluated cases (38.9%), were most commonly reported in ARID1A and SMARCB1. Of the 15 patients screened for hearing impairment, five (33.3%) were affected, peaking at 100% among those with SMARCA4 mutations. NDDs (88.9%, 16/18) were common, and highly consistent across patients harboring mutations in ARID1A, ARID1B, SMARCA4, and SMARCE1, with prevalence rates ranging from 50% to 100%. Feeding difficulties were another prominent feature, affecting 7 of the 15 cases (46.7%). Discussion In this systematic review of 32 fetuses with genetically confirmed Coffin–Siris syndrome (CSS), central nervous system and cardiovascular abnormalities emerged as the most consistent prenatal findings. Multisystem structural involvement was common, and three quarters of fetuses exhibited abnormalities affecting more than one organ system. These observations indicate that CSS frequently manifests during fetal life with detectable structural anomalies, rather than being recognized solely as a postnatal neurodevelopmental condition. Predominance of central nervous system abnormalities Central nervous system (CNS) anomalies were the most frequent prenatal manifestations, particularly ventriculomegaly, corpus callosum abnormalities, and posterior fossa malformations. Similar patterns have been described in prior reports, where agenesis or dysgenesis of the corpus callosum was repeatedly noted as a key prenatal feature [ 5 , 6 ]. Research has found that mutations affecting components of the SWI/SNF complex lead to Coffin-Siris syndrome [ 7 ]. The predominance of midline brain abnormalities is biologically coherent with the known function of the SWI/SNF (BAF) chromatin-remodeling complex, whose components regulate early neurodevelopment, including neural progenitor proliferation and cortical organization [ 8 , 9 ]. Disruption of this pathway may therefore contribute to commissural and ventricular abnormalities detectable in utero. Among genotypes, ARID1A variants were associated with the highest proportion of prenatal CNS involvement in this cohort. Although numbers remain limited, this observation suggests that certain molecular subtypes may predispose to more readily identifiable structural brain anomalies during gestation, which is consistent with previous reports [ 10 ]. Cardiovascular involvement and multisystem presentation Congenital heart defects were identified in one quarter of cases, including conotruncal anomalies and atrioventricular septal defects. Experimental studies have demonstrated that components of the SWI/SNF complex participate in cardiac morphogenesis and transcriptional regulation during heart development [ 11 ], providing a possible mechanistic framework for these observations. Beyond CNS and cardiac anomalies, growth restriction, abnormal amniotic fluid volume, diaphragmatic hernia, and limb abnormalities were recurrent findings [ 12 ]. The high frequency of combined abnormalities reinforces the concept that CSS is a multisystem developmental disorder already established during fetal life [ 2 ]. In clinical practice, isolated findings such as ventriculomegaly or growth restriction may appear nonspecific; however, the presence of concurrent anomalies across organ systems should prompt consideration of an underlying chromatinopathy. Prenatal–postnatal correlation Almost all individuals with CSS exhibited craniofacial abnormalities, with only one case lacking a reported facial phenotype. In addition, nail or fifth-digit abnormalities were observed in 38.9% of cases. Craniofacial anomalies in CSS are thought to arise from disrupted cranial neural crest development associated with ARID1A haploinsufficiency, which contributes to the characteristic facial phenotype [ 13 ]. Despite these characteristic manifestations, classic features such as craniofacial dysmorphism and hypoplasia of the fifth digit or nail were rarely recognized during prenatal assessment. This discrepancy is likely attributable to the limited sensitivity of routine fetal ultrasound for detecting subtle distal limb and facial anomalies rather than their true absence. In contrast, postnatal follow-up frequently revealed neurodevelopmental impairment, hypotonia, seizures, feeding difficulties, and sensory abnormalities—features that cannot be reliably predicted from prenatal imaging alone. These observations underscore an important limitation of structural fetal evaluation: although major malformations may be detectable during pregnancy, functional and neurodevelopmental outcomes remain difficult to anticipate. Prenatal counseling should therefore acknowledge both the structural findings and the uncertainty surrounding long-term developmental trajectories. Implications for genetic testing and counseling The predominance of de novo loss-of-function variants in this cohort is consistent with existing literature and supports the use of trio-based exome sequencing when CSS is suspected prenatally. Given the phenotypic variability and the presence of occasional inherited cases, parental testing remains essential for accurate recurrence risk assessment. The combined rate of stillbirth and pregnancy termination was 43.8%, likely reflects the severity of prenatal structural anomalies and uncertainty regarding prognosis. However, nearly half of affected pregnancies resulted in live birth, and clinical severity varied substantially. Although neurodevelopmental impairment is common, survival into childhood is typical, and some individuals may reach adulthood depending on associated anomalies [ 14 ]. These data underscore the importance of individualized counseling that addresses both the likelihood of neurodevelopmental impairment and the heterogeneity of clinical outcomes. Strengths and limitations This study provides a structured synthesis of reported prenatal imaging findings in genetically confirmed CSS, with systematic extraction of genotype and outcome data. Nevertheless, several limitations must be acknowledged. The analysis is based primarily on published case reports and small series, introducing potential publication bias toward more severe or atypical presentations. Sample sizes within individual genotypes remain small, limiting robust comparative inference. In addition, imaging protocols and follow-up assessments were heterogeneous across reports. Conclusion Coffin–Siris syndrome demonstrates a recurring prenatal pattern characterized predominantly by central nervous system abnormalities, congenital heart defects, and multisystem structural involvement. Although hallmark facial and distal limb features are seldom detectable in utero, recognition of combined structural anomalies should raise suspicion for CSS and prompt comprehensive genomic evaluation. Improved awareness of its prenatal spectrum may enhance diagnostic accuracy, counseling, and perinatal management. Abbreviations CSS: Coffin–Siris syndrome CNS: Central nervous system CVS: Cardiovascular system TOP: Termination of pregnancy NDDs: Neurodevelopmental disorders Declarations Ethics approval and consent to participate Ethical approval was not required for this study, as it was based exclusively on previously published data. Consent for publication Not applicable. Availability of data and materials All data generated or analyzed during this study are included in this published article and its supplementary information files. Competing interests The authors declare that they have no competing interests. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Authors’ contributions Conceptualization: Chunli Jing Data curation: Qiao Zhou Formal analysis: Qiao Zhou Methodology: Qiao Zhou Writing – original draft: Qiao Zhou Writing – review & editing: Chunli Jing Supervision: Chunli Jing All authors read and approved the final manuscript. References Coffin GS, Siris E. Mental retardation with absent fifth fingernail and terminal phalanx. Am J Dis Child. 1970;119(5):433–39. van der Sluijs PJ, Joosten M, Alby C, et al. Discovering a new part of the phenotypic spectrum of Coffin-Siris syndrome in a fetal cohort. Genet Med. 2022;24(8):1753–60. Machol K, Rousseau J, Ehresmann S, et al. Expanding the Spectrum of BAF-Related Disorders: De Novo Variants in SMARCC2 Cause a Syndrome with Intellectual Disability and Developmental Delay. Am J Hum Genet. 2019;104(1):164–78. Schrier SA, Bodurtha JN, Burton B, et al. The Coffin-Siris syndrome: a proposed diagnostic approach and assessment of 15 overlapping cases. Am J Med Genet A. 2012;158A(8):1865–76. Keskinen S, Paakkola T, Mattila M, et al. Prenatal Coffin-Siris Syndrome: Expanding the Phenotypic and Genotypic Spectrum of the Disease. Pediatr Dev Pathol. 2024;27(2):181–6. Tsurusaki Y, Okamoto N, Ohashi H, et al. Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome. Nat Genet. 2012;44(4):376–8. Yu QX, Jing XY, Lin XM, Zhen L, Li DZ. Prenatal diagnosis of Coffin-Siris syndrome: What are the fetal features? Prenat Diagn. 2022;42(12):1488–92. Tuoc TC, Narayanan R, Stoykova A. BAF chromatin remodeling complex: cortical size regulation and beyond. Cell Cycle. 2013;12(18):2953–9. Lessard J, Wu JI, Ranish JA, et al. An essential switch in subunit composition of a chromatin remodeling complex during neural development. Neuron. 2007;55(2):201–5. Slavotinek A, Lefebvre M, Brehin AC, et al. Prenatal presentation of multiple anomalies associated with haploinsufficiency for ARID1A. Eur J Med Genet. 2022;65(2):104407. Castillo-Robles J, Ramírez L, Spaink HP, Lomelí H. smarce1 mutants have a defective endocardium and an increased expression of cardiac transcription factors in zebrafish. Sci Rep. 2018;8(1):15369. Rimoldi M, Rinaldi B, Villa R, et al. Congenital diaphragmatic hernia in Coffin Siris syndrome: Further evidence from two cases. Am J Med Genet A. 2023;191(2):605–11. Barnada SM, Giner de Gracia A, Morenilla-Palao C, et al. ARID1A-BAF coordinates ZIC2 genomic occupancy for epithelial-to-mesenchymal transition in cranial neural crest specification. Am J Hum Genet. 2024;111(10):2232–52. Vasko A, Drivas TG, Schrier Vergano SA. Genotype-Phenotype Correlations in 208 Individuals with Coffin-Siris Syndrome. Genes (Basel). 2021;12(6):937. Additional Declarations No competing interests reported. Supplementary Files PrenatalFindingsinCoffinSirisSyndromebyGeneandOrganSystem.xlsx Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 26 Apr, 2026 Reviewers agreed at journal 20 Apr, 2026 Reviews received at journal 09 Apr, 2026 Reviewers agreed at journal 09 Apr, 2026 Reviewers agreed at journal 07 Apr, 2026 Reviewers invited by journal 07 Apr, 2026 Editor invited by journal 18 Mar, 2026 Editor assigned by journal 18 Mar, 2026 Submission checks completed at journal 18 Mar, 2026 First submitted to journal 10 Mar, 2026 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-9085595","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":621616060,"identity":"64beac3b-2228-4df3-9f21-202742b88b60","order_by":0,"name":"Qiao Zhou","email":"","orcid":"","institution":"Second Affiliated Hospital of Dalian Medical University","correspondingAuthor":false,"prefix":"","firstName":"Qiao","middleName":"","lastName":"Zhou","suffix":""},{"id":621616061,"identity":"fcf6c7c5-9ecb-4af9-96f7-b43b62f2c539","order_by":1,"name":"Chunli Jing","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAsklEQVRIiWNgGAWjYBACxgbm9g8JBhJybOztB4jVwtjG8KHCxpiP50wC0fa0Mc44k5Y4T8LBgDgNzO0H2x7zth1Ob5NgSGD4UbGNCDt6EtuNgVpy26QbDzD2nLlNhJYZjA3SYC0yBxKYGdtI0JLOJpFgQLSWNkmg9xNI0NKT2GwADGTDNmAgHyTKL4bthw8+AEalvHx7+8EHPyqI0dKAxDlAWD0QyBOlahSMglEwCkY2AAA39T54Ht5DCAAAAABJRU5ErkJggg==","orcid":"","institution":"Second Affiliated Hospital of Dalian Medical University","correspondingAuthor":true,"prefix":"","firstName":"Chunli","middleName":"","lastName":"Jing","suffix":""}],"badges":[],"createdAt":"2026-03-10 15:08:42","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9085595/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9085595/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106871187,"identity":"fe7a03a5-5e0d-473c-a002-1c42a5c6f188","added_by":"auto","created_at":"2026-04-14 09:44:46","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":42934,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePRISMA flow diagram of the study selection process.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe flowchart summarizes the systematic literature search and study selection process, from initial database identification to the final inclusion of 32 studies meeting all eligibility criteria.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-9085595/v1/e5e530f10083a6e4aec1ec90.png"},{"id":106871185,"identity":"cf880e4e-64d9-40a1-8fba-aed969854e7a","added_by":"auto","created_at":"2026-04-14 09:44:45","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1391061,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDistribution of prenatal anomalies by organ system.\u003c/strong\u003e Stacked bars show the percentage of CNS, CVS, and IUGR anomalies across five prenatal findings. Values indicate proportions within each finding.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-9085595/v1/4b6ebf316be5e2fd3536eadc.png"},{"id":106871186,"identity":"53bd5e15-7c44-4a64-8e76-2eb20a47a741","added_by":"auto","created_at":"2026-04-14 09:44:45","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":882567,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eGenotype-organ system association heatmap.\u003c/strong\u003e The heatmap displays the distribution of gene variants across organ systems (CNS, CVS, IUGR, CDH, Limb, Other). Color intensity reflects variant frequency, with numerical values indicating enrichment levels.\u003c/p\u003e","description":"","filename":"Figure3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-9085595/v1/9b4ce445f721da37df8deaac.jpeg"},{"id":106871193,"identity":"754ec995-e49f-41ba-a013-e32c21e19ad3","added_by":"auto","created_at":"2026-04-14 09:44:50","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":153932,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePrenatal vs. postnatal detection rates in live-born infants.\u003c/strong\u003e Bar chart comparing the incidence of anomalies across five categories between prenatally and postnatally diagnosed cases. Percentages highlight differences in detection rates.\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-9085595/v1/29217a4e0c0c654b8f46d3c8.png"},{"id":106961936,"identity":"e9e7611d-02ca-42f4-be5a-5243d1949da7","added_by":"auto","created_at":"2026-04-15 09:27:53","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3453024,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9085595/v1/cae01740-c4db-49b5-bc47-30959815c063.pdf"},{"id":106871192,"identity":"38da500a-f000-4597-b29e-76a24b003ad1","added_by":"auto","created_at":"2026-04-14 09:44:50","extension":"xlsx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":27185,"visible":true,"origin":"","legend":"","description":"","filename":"PrenatalFindingsinCoffinSirisSyndromebyGeneandOrganSystem.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-9085595/v1/759a579b96fff9225e549cd4.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Prenatal Sonographic Features and Genotype–Phenotype Correlations in Coffin–Siris Syndrome: A Systematic Case Analysis of 32 Fetuses","fulltext":[{"header":"Background","content":"\u003cp\u003eCoffin\u0026ndash;Siris syndrome (CSS) is a rare genetic disorder characterized primarily by neurodevelopmental delay, typically accompanied by hypoplasia or aplasia of the fifth fingernail or toenail, distinctive facial features, hypertrichosis, and variable congenital anomalies. The syndrome was first described in 1970 by Coffin and Siris in patients presenting with intellectual disability and absent or underdeveloped fifth distal phalanges and nails [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Beyond its characteristic limb and facial manifestations, CSS is frequently associated with multisystem involvement. Reported anomalies include congenital heart defects, diaphragmatic hernia, and other structural malformations [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], as well as visual and hearing impairments, epilepsy, and severe cognitive dysfunction [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Most affected individuals exhibit moderate to profound developmental delay and require long-term medical, rehabilitative, and social support, resulting in a substantial burden on families and healthcare systems [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Overall, the prognosis of CSS is considered unfavorable, particularly in cases with early-onset seizures or major structural anomalies.\u003c/p\u003e \u003cp\u003eDespite its clinical significance, prenatal identification of CSS remains challenging. The phenotypic spectrum is highly heterogeneous, and many hallmark features evolve progressively during gestation or become apparent only after birth [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Existing literature has focused largely on postnatal clinical phenotypes and molecular findings, whereas systematic descriptions of prenatal ultrasound manifestations are scarce. Consequently, many cases are diagnosed only in the postnatal period, limiting opportunities for timely prenatal counseling and informed decision-making.\u003c/p\u003e \u003cp\u003eIn this context, a comprehensive characterization of prenatal ultrasound features associated with Coffin\u0026ndash;Siris syndrome, particularly in relation to different genetic subtypes, is of considerable clinical importance. The present study aims to systematically review reported cases to delineate the prenatal sonographic spectrum of CSS and explore genotype\u0026ndash;phenotype correlations, thereby providing imaging-based evidence to support improved prenatal recognition and counseling.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eStudy design\u003c/p\u003e \u003cp\u003eThis systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. As the study was based exclusively on previously published data, ethical approval was not required.\u003c/p\u003e \u003cp\u003eSearch strategy\u003c/p\u003e \u003cp\u003eA comprehensive literature search was performed in PubMed, Embase, and Scopus from database inception to September 1, 2025. The search strategy combined controlled vocabulary (MeSH and Emtree terms) and free-text keywords related to Coffin\u0026ndash;Siris syndrome and prenatal imaging.\u003c/p\u003e \u003cp\u003eThe following terms were used in various combinations:\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eCoffin\u0026ndash;Siris syndrome,\u0026rdquo; \u0026ldquo;CSS,\u0026rdquo; \u0026ldquo;BAF complex,\u0026rdquo; \u0026ldquo;SWI/SNF,\u0026rdquo; \u0026ldquo;prenatal diagnosis,\u0026rdquo; \u0026ldquo;prenatal ultrasound,\u0026rdquo; \u0026ldquo;fetal imaging,\u0026rdquo; \u0026ldquo;fetal MRI,\u0026rdquo; \u0026ldquo;prenatal screening,\u0026rdquo; and \u0026ldquo;congenital anomalies.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eThe search was restricted to studies published in English. Reference lists of included articles were manually screened to identify additional relevant reports.\u003c/p\u003e \u003cp\u003eEligibility criteria\u003c/p\u003e \u003cp\u003eStudies were included if they met the following criteria:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eReported fetuses with genetically confirmed Coffin\u0026ndash;Siris syndrome;\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eProvided documented prenatal imaging findings (ultrasound and/or fetal MRI);\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003ePresented sufficient clinical and genetic information for data extraction.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cp\u003eStudies were excluded if:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003ePrenatal imaging findings were not described;\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eGenetic confirmation was unavailable;\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eData were incomplete or duplicated in other reports.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cp\u003eStudy selection\u003c/p\u003e \u003cp\u003eAfter removal of duplicates, two reviewers independently screened titles and abstracts for eligibility. Full texts of potentially relevant articles were assessed independently. Disagreements were resolved through discussion and consensus. The selection process is illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Publication bias was not formally assessed due to the nature of case reports/series, but the potential impact of selective reporting is addressed in the limitations.\u003c/p\u003e \u003cp\u003eData extraction\u003c/p\u003e \u003cp\u003eData were extracted independently by two investigators using a standardized data collection form. Extracted variables included: Maternal age, Gestational age at diagnosis, Fetal sex, Gene variant and inheritance pattern, Prenatal imaging findings by organ system, Pregnancy outcome, Postnatal clinical features.\u003c/p\u003e \u003cp\u003eQuality assessment\u003c/p\u003e \u003cp\u003eGiven that most included studies were case reports or case series, methodological quality was assessed using an adapted version of the CARE (Case Report) checklist to evaluate completeness of reporting. Formal assessment of the certainty of evidence was not performed, as all included studies were case reports or small case series without comparators. However, the diagnostic certainty of CSS in this cohort is high, as all cases had molecular confirmation.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eDescriptive statistical analysis was performed using SPSS version 26.0 (IBM Corp., Armonk, NY, USA). Continuous variables were expressed as ranges or medians when appropriate. Categorical variables were summarized as frequencies and percentages. Python (version 3.9; Python Software Foundation, Wilmington, DE, USA) was used for additional data organization and visualization. To explore potential sources of heterogeneity in prenatal phenotypes, we performed descriptive subgroup analyses based on the affected gene. Findings were compared across gene subgroups to identify patterns of organ system involvement, although no formal statistical testing was conducted due to small sample sizes in certain genotype groups.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eStudy characteristics and genetic findings\u003c/p\u003e \u003cp\u003eA total of 32 prenatally diagnosed cases were included, with the distribution of pathogenic variants, inheritance patterns, and pregnancy outcomes summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, stratified by gene. These cases were drawn from publications between 2016 and 2025. Maternal age ranged from 19 to 38 years, and most pregnancies were sporadic, with de novo pathogenic variants identified in the majority of cases. Among the cases where fetal sex was reported, the male-to-female ratio was 1.07:1. Pathogenic or likely pathogenic variants were identified in genes encoding components of the BAF/SWI\u0026ndash;SNF chromatin-remodeling complex or related regulatory genes, including ARID1A representing the largest subgroup (n\u0026thinsp;=\u0026thinsp;14), followed by SMARCA4 (n\u0026thinsp;=\u0026thinsp;4), SMARCB1 (n\u0026thinsp;=\u0026thinsp;3), ARID1B (n\u0026thinsp;=\u0026thinsp;3), SMARCC2 (n\u0026thinsp;=\u0026thinsp;1), SMARCD1 (n\u0026thinsp;=\u0026thinsp;1), ARID2 (n\u0026thinsp;=\u0026thinsp;1), SMARCA2 (n\u0026thinsp;=\u0026thinsp;1), SMARCE1 (n\u0026thinsp;=\u0026thinsp;3), and SOX11(n\u0026thinsp;=\u0026thinsp;1).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eStudy characteristics, variant types, inheritance patterns, and pregnancy outcomes stratified by gene (n\u0026thinsp;=\u0026thinsp;32).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"12\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCategory\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003cp\u003en/N (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eARID1A (n\u0026thinsp;=\u0026thinsp;14)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eARID1B (n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eARID2 (n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSMARCA2 (n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eSMARCA4 (n\u0026thinsp;=\u0026thinsp;4)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eSMARCB1 (n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eSMARCC2 (n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eSMARCD1 (n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eSMARCE1 (n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003eSOX11\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14 (43.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6 (42.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1 (25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e2 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e2 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15 (46.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e1 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e1 (100.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNot evaluated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (9.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1 (25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVariant type\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLOF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17 (53.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11 (78.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMissense\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14 (43.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (21.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e2 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e3 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e1 (100.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eInheritance\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDe novo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e29 (90.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e13 (92.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e3 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e3 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e1 (100.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInherited\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (9.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePregnancy outcome\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLive birth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e18 (56.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6 (42.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e3 (75.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e2 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e2 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e1 (100.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTOP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12 (37.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1 (25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e1 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIUFD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"12\"\u003eLOF, loss-of-function variants including nonsense, frameshift, and canonical splice-site variants; Other variant types include in-frame variants or complex rearrangements; TOP, termination of pregnancy; IUFD, intrauterine fetal death. Percentages are calculated within each gene column.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAmong these, ARID1A-related variants were the most frequently reported, accounting for nearly half of the cases, followed by SMARCA4 and SMARCB1. Most variants were loss-of-function mutations, including frameshift, nonsense, or splice-site variants, consistent with haploinsufficiency.\u003c/p\u003e \u003cp\u003eInheritance information was available for most cases, revealing that 90.6% of variants were de novo, with only a few inherited cases, often associated with milder prenatal phenotype.\u003c/p\u003e \u003cp\u003ePrenatal ultrasonographic findings\u003c/p\u003e \u003cp\u003ePrenatal structural abnormalities were observed across multiple organ systems (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Prenatal ultrasound abnormalities were detected as early as the first trimester, with gestational age at diagnosis ranging from 12 to 32 weeks. Central nervous system (CNS) abnormalities constituted the most frequent prenatal findings, observed in 18 of 32 cases (56.3%). The predominant CNS anomalies were ventriculomegaly or hydrocephalus, affecting 13 individuals (40.6%), and abnormalities of the corpus callosum, present in 7 cases (21.9%). Posterior fossa abnormalities (3 cases, 9.4%), cerebellar anomalies (4 cases, 12.5%), and encephalocele (1 case, 3.1%) were also observed. ARID1A demonstrated the highest frequency, with CNS involvement identified in 11 of 14 cases (78.6%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Despite the limited number of reported cases, the incidence among other phenotypic associations is below 35%.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePrenatal imaging findings stratified by organ system and gene (n\u0026thinsp;=\u0026thinsp;32).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"12\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOrgan system\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal n/N (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eARID1A (n\u0026thinsp;=\u0026thinsp;14)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eARID1B (n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eARID2 (n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSMARCA2 (n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eSMARCA4 (n\u0026thinsp;=\u0026thinsp;4)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eSMARCB1 (n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eSMARCC2 (n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eSMARCD1 (n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eSMARCE1 (n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003eSOX11\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCNS anomalies\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVentriculomegaly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13 (40.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10 (71.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e2 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCorpus callosum anomaly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6 (18.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (21.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1 (25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e1 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e1 (100.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePosterior fossa anomaly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (9.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebellar anomaly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1 (25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEncephalocele\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther CNS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCVS anomalies\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConotruncal defect\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e2 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAVSD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (9.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1 (25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e2 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSeptal defect\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther CVS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1 (25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOther systems\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIUGR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6 (18.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e2 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e1 (100.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePolyhydramnios\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5 (15.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (21.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1 (25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOligohydramnios\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCDH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1 (25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLimb anomaly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e1 (100.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIncreased NT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRenal anomaly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSingle umbilical artery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (9.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1 (25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOmphalocele\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphangioma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"12\"\u003eCategories are not mutually exclusive. n/N (%) indicates number of affected cases per total cases within each gene group. Categories are not mutually exclusive; some fetuses presented with multiple anomalies. CNS, central nervous system; CVS, cardiovascular system; AVSD, atrioventricular septal defect; CDH, congenital diaphragmatic hernia; IUGR, intrauterine growth restriction; NT, nuchal translucency.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eCardiovascular system (CVS) abnormalities were identified prenatally in 8 of 32 cases (25.0%). The spectrum included conotruncal defects, such as tetralogy of Fallot and functional single ventricle (2 cases, 6.3%); atrioventricular septal defects (3 cases, 9.4%); and other septal defects (2 cases, 6.3%). One case had a right ventricular dimension at the upper limit of normal (1 cases, 3.1%). SMARCE1 showed the highest proportional involvement, with cardiac defects reported in 66.7% of cases. Cardiac involvement was less frequently reported in other genotypes.\u003c/p\u003e \u003cp\u003eBeyond CNS and CVS anomalies, the most common were intrauterine growth restriction (IUGR, 6 cases, 18.9%) and abnormalities of amniotic fluid volume (5 cases, 15.6%), comprising both polyhydramnios (5 cases, 15.6%) and oligohydramnios (1 case, 3.1%). Structural anomalies included congenital diaphragmatic hernia (4 cases, 12.5%), limb abnormalities (4 cases, 12.5%), and increased nuchal translucency (\u0026ge;\u0026thinsp;3.0 mm, 2 cases, 6.3%). Placental or umbilical cord abnormalities were noted in 5 cases (15.6%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Most genotypes were associated with two or more abnormalities (24/32, 75%).\u003c/p\u003e \u003cp\u003ePregnancy outcomes and postnatal findings\u003c/p\u003e \u003cp\u003eAdverse pregnancy outcomes were common. Termination of pregnancy (TOP) or stillbirth were performed in 14 of 32 cases (43.8%), most frequently prompted by severe central nervous system malformations, complex cardiovascu lar defects, or multisystem anomalies identified on prenatal imaging. Intrauterine fetal demise occurred in two cases (6.3%), while 18 pregnancies (56.3%) resulted in live birth (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePostnatal phenotypic features in live-born cases stratified by gene (n\u0026thinsp;=\u0026thinsp;18).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhenotype\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal n/N (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eARID1A (n\u0026thinsp;=\u0026thinsp;6)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eARID1B (n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSMARCA2 (n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSMARCA4 (n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eSMARCB1 (n\u0026thinsp;=\u0026thinsp;2)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eSMARCE1 (n\u0026thinsp;=\u0026thinsp;2)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eSOX11\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeurodevelopmental disorder\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16 (88.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e2 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1(100.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypotonia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSeizure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (11.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (16.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNail anomaly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7 (38.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e2 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFacial dysmorphism\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17 (94.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e2 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e1 (100.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOphthalmologic abnormalities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7 (38.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHearing loss\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5 (27.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003ePercentages are calculated within each gene column. Only live-born cases with available postnatal follow-up data were included. There were two cases without neurodevelopmental assessment. Neurodevelopmental disorder includes global developmental delay, intellectual disability, or autism spectrum disorder.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAmong the live-born infants, gestational age at delivery ranged from 30 to 40 weeks. A marked discrepancy between prenatal detection and postnatal diagnosis was observed (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). While CNS structural anomalies were identified prenatally in 8 of 18 live-born cases (44.4%), postnatal evaluation revealed abnormalities in 11 cases (61.1%). Despite being rarely detectable prenatally, characteristic facial dysmorphism was identified in all live-born and stillborn cases, save for nine individuals lacking postnatal or post-mortem records.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of prenatal detection and postnatal manifestation of major phenotypic abnormalities (live-born cohort, n\u0026thinsp;=\u0026thinsp;18).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbnormality Category\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePrenatal (All cases, n\u0026thinsp;=\u0026thinsp;32)\u003c/p\u003e \u003cp\u003e(n %)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePrenatal (Live-born, n\u0026thinsp;=\u0026thinsp;18)\u003c/p\u003e \u003cp\u003e(n %)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePostnatal (Live-born, n\u0026thinsp;=\u0026thinsp;18)\u003c/p\u003e \u003cp\u003e(n %)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCNS structural anomalies\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e18 (56.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8 (44.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e11 (61.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCVS anomalies\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8 (25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4 (22.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e9 (50.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLimb/nail anomalies\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (11.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e13 (70.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFacial dysmorphism\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e17 (94.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCDH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (17.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5 (27.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eSome cases had multiple cardiac anomalies. Prenatal (All cases) refers to all 32 fetuses. Prenatal (Live-born) refers only to the 18 live-born cases. There was one case without reported facial findings. Postnatal data were available only for live-born cases. Categories are not mutually exclusive. CNS, central nervous system; CVS, cardiovascular system; CDH, congenital diaphragmatic hernia.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAmong the 18 live-born infants, one died on postnatal day 3 and one had not undergone evaluation at the time of reporting; of the remaining cases, 16 were found to have neurodevelopmental abnormalities, including global developmental delay, intellectual disability, hypotonia, and seizures. Limb and nail anomalies were frequently observed (17 cases, 94.4%), particularly involving the fifth digits. In addition, multisystem involvement was common, affecting the cardiovascular, gastrointestinal, genitourinary, and respiratory systems.\u003c/p\u003e \u003cp\u003eOphthalmological abnormalities were identified in 7 of the 18 evaluated cases (38.9%), were most commonly reported in ARID1A and SMARCB1. Of the 15 patients screened for hearing impairment, five (33.3%) were affected, peaking at 100% among those with SMARCA4 mutations. NDDs (88.9%, 16/18) were common, and highly consistent across patients harboring mutations in ARID1A, ARID1B, SMARCA4, and SMARCE1, with prevalence rates ranging from 50% to 100%. Feeding difficulties were another prominent feature, affecting 7 of the 15 cases (46.7%).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this systematic review of 32 fetuses with genetically confirmed Coffin\u0026ndash;Siris syndrome (CSS), central nervous system and cardiovascular abnormalities emerged as the most consistent prenatal findings. Multisystem structural involvement was common, and three quarters of fetuses exhibited abnormalities affecting more than one organ system. These observations indicate that CSS frequently manifests during fetal life with detectable structural anomalies, rather than being recognized solely as a postnatal neurodevelopmental condition.\u003c/p\u003e\n\u003ch3\u003ePredominance of central nervous system abnormalities\u003c/h3\u003e\n\u003cp\u003eCentral nervous system (CNS) anomalies were the most frequent prenatal manifestations, particularly ventriculomegaly, corpus callosum abnormalities, and posterior fossa malformations. Similar patterns have been described in prior reports, where agenesis or dysgenesis of the corpus callosum was repeatedly noted as a key prenatal feature [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Research has found that mutations affecting components of the SWI/SNF complex lead to Coffin-Siris syndrome [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The predominance of midline brain abnormalities is biologically coherent with the known function of the SWI/SNF (BAF) chromatin-remodeling complex, whose components regulate early neurodevelopment, including neural progenitor proliferation and cortical organization [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Disruption of this pathway may therefore contribute to commissural and ventricular abnormalities detectable in utero.\u003c/p\u003e \u003cp\u003eAmong genotypes, ARID1A variants were associated with the highest proportion of prenatal CNS involvement in this cohort. Although numbers remain limited, this observation suggests that certain molecular subtypes may predispose to more readily identifiable structural brain anomalies during gestation, which is consistent with previous reports [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eCardiovascular involvement and multisystem presentation\u003c/h3\u003e\n\u003cp\u003eCongenital heart defects were identified in one quarter of cases, including conotruncal anomalies and atrioventricular septal defects. Experimental studies have demonstrated that components of the SWI/SNF complex participate in cardiac morphogenesis and transcriptional regulation during heart development [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], providing a possible mechanistic framework for these observations.\u003c/p\u003e \u003cp\u003eBeyond CNS and cardiac anomalies, growth restriction, abnormal amniotic fluid volume, diaphragmatic hernia, and limb abnormalities were recurrent findings [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The high frequency of combined abnormalities reinforces the concept that CSS is a multisystem developmental disorder already established during fetal life [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. In clinical practice, isolated findings such as ventriculomegaly or growth restriction may appear nonspecific; however, the presence of concurrent anomalies across organ systems should prompt consideration of an underlying chromatinopathy.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003ePrenatal\u0026ndash;postnatal correlation\u003c/h2\u003e \u003cp\u003eAlmost all individuals with CSS exhibited craniofacial abnormalities, with only one case lacking a reported facial phenotype. In addition, nail or fifth-digit abnormalities were observed in 38.9% of cases. Craniofacial anomalies in CSS are thought to arise from disrupted cranial neural crest development associated with ARID1A haploinsufficiency, which contributes to the characteristic facial phenotype [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite these characteristic manifestations, classic features such as craniofacial dysmorphism and hypoplasia of the fifth digit or nail were rarely recognized during prenatal assessment. This discrepancy is likely attributable to the limited sensitivity of routine fetal ultrasound for detecting subtle distal limb and facial anomalies rather than their true absence.\u003c/p\u003e \u003cp\u003eIn contrast, postnatal follow-up frequently revealed neurodevelopmental impairment, hypotonia, seizures, feeding difficulties, and sensory abnormalities\u0026mdash;features that cannot be reliably predicted from prenatal imaging alone.\u003c/p\u003e \u003cp\u003eThese observations underscore an important limitation of structural fetal evaluation: although major malformations may be detectable during pregnancy, functional and neurodevelopmental outcomes remain difficult to anticipate. Prenatal counseling should therefore acknowledge both the structural findings and the uncertainty surrounding long-term developmental trajectories.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eImplications for genetic testing and counseling\u003c/h3\u003e\n\u003cp\u003eThe predominance of de novo loss-of-function variants in this cohort is consistent with existing literature and supports the use of trio-based exome sequencing when CSS is suspected prenatally. Given the phenotypic variability and the presence of occasional inherited cases, parental testing remains essential for accurate recurrence risk assessment.\u003c/p\u003e \u003cp\u003eThe combined rate of stillbirth and pregnancy termination was 43.8%, likely reflects the severity of prenatal structural anomalies and uncertainty regarding prognosis. However, nearly half of affected pregnancies resulted in live birth, and clinical severity varied substantially. Although neurodevelopmental impairment is common, survival into childhood is typical, and some individuals may reach adulthood depending on associated anomalies [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. These data underscore the importance of individualized counseling that addresses both the likelihood of neurodevelopmental impairment and the heterogeneity of clinical outcomes.\u003c/p\u003e\n\u003ch3\u003eStrengths and limitations\u003c/h3\u003e\n\u003cp\u003eThis study provides a structured synthesis of reported prenatal imaging findings in genetically confirmed CSS, with systematic extraction of genotype and outcome data. Nevertheless, several limitations must be acknowledged. The analysis is based primarily on published case reports and small series, introducing potential publication bias toward more severe or atypical presentations. Sample sizes within individual genotypes remain small, limiting robust comparative inference. In addition, imaging protocols and follow-up assessments were heterogeneous across reports.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eCoffin\u0026ndash;Siris syndrome demonstrates a recurring prenatal pattern characterized predominantly by central nervous system abnormalities, congenital heart defects, and multisystem structural involvement. Although hallmark facial and distal limb features are seldom detectable in utero, recognition of combined structural anomalies should raise suspicion for CSS and prompt comprehensive genomic evaluation. Improved awareness of its prenatal spectrum may enhance diagnostic accuracy, counseling, and perinatal management.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCSS: Coffin\u0026ndash;Siris syndrome\u003c/p\u003e\n\u003cp\u003eCNS: Central nervous system\u003c/p\u003e\n\u003cp\u003eCVS: Cardiovascular system\u003c/p\u003e\n\u003cp\u003eTOP: Termination of pregnancy\u003c/p\u003e\n\u003cp\u003eNDDs: Neurodevelopmental disorders\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval was not required for this study, as it was based exclusively on previously published data.\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\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analyzed during this study are included in this published article and its supplementary information files.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization: Chunli Jing\u003c/p\u003e\n\u003cp\u003eData curation: Qiao Zhou\u003c/p\u003e\n\u003cp\u003eFormal analysis: Qiao Zhou\u003c/p\u003e\n\u003cp\u003eMethodology: Qiao Zhou\u003c/p\u003e\n\u003cp\u003eWriting \u0026ndash; original draft: Qiao Zhou\u003c/p\u003e\n\u003cp\u003eWriting \u0026ndash; review \u0026amp; editing: Chunli Jing\u003c/p\u003e\n\u003cp\u003eSupervision: Chunli Jing\u003c/p\u003e\n\u003cp\u003eAll authors read and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCoffin GS, Siris E. Mental retardation with absent fifth fingernail and terminal phalanx. Am J Dis Child. 1970;119(5):433\u0026ndash;39.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan der Sluijs PJ, Joosten M, Alby C, et al. Discovering a new part of the phenotypic spectrum of Coffin-Siris syndrome in a fetal cohort. Genet Med. 2022;24(8):1753\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMachol K, Rousseau J, Ehresmann S, et al. Expanding the Spectrum of BAF-Related Disorders: De Novo Variants in SMARCC2 Cause a Syndrome with Intellectual Disability and Developmental Delay. Am J Hum Genet. 2019;104(1):164\u0026ndash;78.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchrier SA, Bodurtha JN, Burton B, et al. The Coffin-Siris syndrome: a proposed diagnostic approach and assessment of 15 overlapping cases. Am J Med Genet A. 2012;158A(8):1865\u0026ndash;76.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKeskinen S, Paakkola T, Mattila M, et al. Prenatal Coffin-Siris Syndrome: Expanding the Phenotypic and Genotypic Spectrum of the Disease. Pediatr Dev Pathol. 2024;27(2):181\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTsurusaki Y, Okamoto N, Ohashi H, et al. Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome. Nat Genet. 2012;44(4):376\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYu QX, Jing XY, Lin XM, Zhen L, Li DZ. Prenatal diagnosis of Coffin-Siris syndrome: What are the fetal features? Prenat Diagn. 2022;42(12):1488\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTuoc TC, Narayanan R, Stoykova A. BAF chromatin remodeling complex: cortical size regulation and beyond. Cell Cycle. 2013;12(18):2953\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLessard J, Wu JI, Ranish JA, et al. An essential switch in subunit composition of a chromatin remodeling complex during neural development. Neuron. 2007;55(2):201\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSlavotinek A, Lefebvre M, Brehin AC, et al. Prenatal presentation of multiple anomalies associated with haploinsufficiency for ARID1A. Eur J Med Genet. 2022;65(2):104407.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCastillo-Robles J, Ram\u0026iacute;rez L, Spaink HP, Lomel\u0026iacute; H. smarce1 mutants have a defective endocardium and an increased expression of cardiac transcription factors in zebrafish. Sci Rep. 2018;8(1):15369.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRimoldi M, Rinaldi B, Villa R, et al. Congenital diaphragmatic hernia in Coffin Siris syndrome: Further evidence from two cases. Am J Med Genet A. 2023;191(2):605\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBarnada SM, Giner de Gracia A, Morenilla-Palao C, et al. ARID1A-BAF coordinates ZIC2 genomic occupancy for epithelial-to-mesenchymal transition in cranial neural crest specification. Am J Hum Genet. 2024;111(10):2232\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVasko A, Drivas TG, Schrier Vergano SA. Genotype-Phenotype Correlations in 208 Individuals with Coffin-Siris Syndrome. Genes (Basel). 2021;12(6):937.\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":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Coffin–Siris syndrome, prenatal diagnosis, ultrasound, genotype-phenotype correlation, pregnancy outcome","lastPublishedDoi":"10.21203/rs.3.rs-9085595/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9085595/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eCoffin\u0026ndash;Siris syndrome (CSS) is a rare multisystem genetic disorder caused by pathogenic variants in genes encoding components of the BAF/SWI\u0026ndash;SNF chromatin-remodeling complex. Prenatal recognition is difficult because the phenotypic spectrum is heterogeneous and many characteristic features emerge only after birth. We aimed to summarize the prenatal imaging spectrum of CSS and explore potential genotype\u0026ndash;phenotype associations.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA systematic review of PubMed, Embase, and Scopus was performed to identify reported cases of prenatally diagnosed CSS with documented fetal imaging findings. Cases published between 2016 and 2025 with molecular confirmation and detailed prenatal ultrasound data were included. Clinical characteristics, genetic variants, prenatal imaging findings, and pregnancy outcomes were extracted and analyzed descriptively.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThirty-two fetuses with genetically confirmed CSS were included. Structural abnormalities were most frequently identified in the central nervous system (18/32, 56.3%), particularly ventriculomegaly, corpus callosum abnormalities, and posterior fossa malformations. Congenital heart defects were present in 8 cases (25.0%). Other recurrent findings included intrauterine growth restriction, abnormal amniotic fluid volume, diaphragmatic hernia, and limb anomalies. Multisystem involvement (\u0026ge;\u0026thinsp;2 organ systems) was observed in 24 fetuses (75.0%). Variants in ARID1A were associated with the highest frequency of prenatal central nervous system abnormalities (78.6%). Despite these structural findings, typical postnatal features of CSS, including craniofacial dysmorphism and fifth-digit or nail hypoplasia, were rarely detectable prenatally.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eCoffin\u0026ndash;Siris syndrome may present during fetal life with a pattern of multisystem structural anomalies, most commonly involving the central nervous and cardiovascular systems. However, hallmark craniofacial and distal limb features are often not apparent on prenatal imaging. Recognition of combined structural abnormalities should prompt consideration of CSS and may support early genomic testing and prenatal counseling.\u003c/p\u003e","manuscriptTitle":"Prenatal Sonographic Features and Genotype–Phenotype Correlations in Coffin–Siris Syndrome: A Systematic Case Analysis of 32 Fetuses","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-14 09:44:12","doi":"10.21203/rs.3.rs-9085595/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-04-26T19:51:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"216951976814674688445577374939283767240","date":"2026-04-20T06:03:38+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-09T11:41:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"58023747570088252963213908028414136979","date":"2026-04-09T07:41:26+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"211988127024241288667874647564225791849","date":"2026-04-07T07:20:54+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-07T07:11:35+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-03-18T10:58:47+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-18T10:49:46+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-18T10:49:38+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pregnancy and Childbirth","date":"2026-03-10T15:04:21+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9bcbd51c-d29d-421f-888c-603b674910f2","owner":[],"postedDate":"April 14th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-14T09:44:12+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-14 09:44:12","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9085595","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9085595","identity":"rs-9085595","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}