Coffin-Siris Syndrome Confirmed by an ARID1B Mutation: A Case Report

Abstract

Introduction: Coffin-Siris syndrome (CSS) is a rare disorder of the SWI/SNF-related intellectual disability group. It typically presents with global developmental delay, variable intellectual disability, facial dysmorphism, and hypoplasia or absence of the distal phalanges, especially of the fifth digit. Among the implicated genes, ARID1B is the most frequently mutated, explaining most confirmed cases. Case Presentation: We report a 14-year-old boy with developmental delay, moderate intellectual disability, characteristic dysmorphic features, bilateral hypoplasia of the fifth digits, dorsolumbar scoliosis, and a history of bilateral cryptorchidism. Additional findings included café-au-lait macules, which are rarely described in CSS. Complementary investigations were unremarkable, including a normal karyotype. Exome sequencing identified a novel heterozygous deletion in ARID1B (NM_001374828.1:c.2964del; NP_001361757.1:p.Ser989ValfsTer20), leading to a frameshift and predicted protein truncation. This variant was absent from population databases and previously unreported, and was classified as likely pathogenic, confirming CSS type 1 (OMIM:135900). Conclusion: This case highlights a typical ARID1B-related Coffin-Siris phenotype and contributes a novel variant to the molecular spectrum. It also emphasizes the role of next-generation sequencing in confirming rare syndromes, supporting multidisciplinary management and genetic counseling.