Costello syndrome

Costello syndrome (also known as faciocutaneoskeletal syndrome or FCS syndrome) is a rare multisystem genetic disorder caused by germline mutations in the HRAS gene. It belongs to a group of conditions known as RASopathies, which involve dysregulation of the Ras/MAPK signaling pathway. Costello syndrome affects multiple body systems including the cardiovascular, musculoskeletal, integumentary (skin), and neurological systems. Nearly all cases arise from de novo (new) mutations, meaning they are not inherited from an affected parent. Key clinical features include failure to thrive and severe feeding difficulties in infancy, short stature, distinctive coarse facial features (full lips, large mouth, prominent nasolabial folds), loose and redundant skin especially on the hands and feet, deep palmar and plantar creases, curly or sparse hair, intellectual disability (typically mild to moderate), and cardiac abnormalities such as hypertrophic cardiomyopathy and cardiac arrhythmias. Papillomata (benign wart-like growths) around the nose and mouth are a characteristic finding that often develop in childhood. Musculoskeletal features include joint hypermobility followed by progressive joint contractures, tight Achilles tendons, and ulnar deviation of the wrists. Individuals with Costello syndrome have an increased predisposition to certain tumors, including rhabdomyosarcoma, neuroblastoma, and transitional cell carcinoma of the bladder, necessitating regular tumor surveillance. There is no cure for Costello syndrome; management is supportive and multidisciplinary, involving cardiology monitoring, nutritional support (often requiring gastrostomy tube feeding in infancy), developmental therapies including speech, occupational, and physical therapy, orthopedic management, and regular screening for malignancies. Growth hormone therapy has been used in some cases but requires careful consideration given the tumor predisposition. Early intervention programs are important for optimizing developmental outcomes.

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

Common questions about Costello syndrome