Coffin-Siris syndrome

Coffin-Siris syndrome (CSS), also known as fifth digit syndrome, is a rare congenital disorder characterized by intellectual disability, coarse facial features, and hypoplasia or absence of the nail and/or distal phalanx of the fifth fingers and toes. The syndrome affects multiple body systems including the nervous system, skeletal system, and craniofacial structures. CSS is caused by mutations in genes encoding subunits of the BAF (BRG1/BRM-associated factor) chromatin remodeling complex, including ARID1B (the most commonly mutated gene, accounting for approximately 50-75% of cases), SMARCB1, SMARCA4, SMARCE1, ARID1A, ARID2, SOX11, DPF2, and SMARCC2. Key clinical features include growth deficiency (often prenatal onset), feeding difficulties in infancy, microcephaly, sparse scalp hair, thick eyebrows, long eyelashes, a wide mouth with thick lips, a flat nasal bridge, and the characteristic nail and digital hypoplasia. Intellectual disability ranges from mild to severe, and speech delay is common. Additional features may include hearing loss, cardiac defects, renal anomalies, and brain abnormalities such as corpus callosum hypoplasia or Dandy-Walker malformation. Hypotonia is frequently present in infancy and may contribute to feeding and motor difficulties. There is no cure for Coffin-Siris syndrome, and management is supportive and multidisciplinary. Treatment focuses on early intervention programs including speech therapy, occupational therapy, and physical therapy to optimize developmental outcomes. Regular monitoring for associated complications such as cardiac, renal, and hearing abnormalities is recommended. Feeding support may be necessary in infancy. Genetic counseling is important for affected families, as most cases arise from de novo mutations, though familial cases have been reported.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Coffin-Siris syndrome