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

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.