Cardiofaciocutaneous syndrome

Cardiofaciocutaneous (CFC) syndrome is a rare genetic disorder belonging to the RASopathy family of conditions, which are caused by dysregulation of the RAS-MAPK signaling pathway. CFC syndrome is characterized by a distinctive combination of cardiac abnormalities, characteristic facial features, ectodermal (skin, hair, and nail) anomalies, and developmental delays. The condition is caused by mutations in genes involved in the RAS-MAPK pathway, most commonly BRAF (approximately 75% of cases), but also MAP2K1 (MEK1), MAP2K2 (MEK2), and KRAS. Cardiac defects are present in the majority of individuals and commonly include pulmonary valve stenosis, hypertrophic cardiomyopathy, atrial septal defects, and other structural heart abnormalities. Characteristic facial features include a high forehead, bitemporal narrowing, down-slanting palpebral fissures, a short nose with a depressed nasal bridge, and low-set posteriorly rotated ears. Ectodermal findings are a hallmark of the syndrome and include sparse, curly, or absent hair; dry, hyperkeratotic skin; keratosis pilaris; and dystrophic or absent nails. Affected individuals typically have moderate to severe intellectual disability, feeding difficulties in infancy, failure to thrive, short stature, and hypotonia. There is currently no cure for CFC syndrome, and management is supportive and multidisciplinary. Treatment focuses on addressing specific symptoms, including cardiac surveillance and intervention when needed, nutritional support (sometimes requiring gastrostomy tube feeding), physical and occupational therapy, speech therapy, and management of seizures, which occur in approximately 50% of affected individuals. Dermatologic care for skin manifestations and regular developmental assessments are also important components of care. Research into targeted therapies, including MEK inhibitors, is ongoing but remains largely investigational for this condition.

Common questions about Cardiofaciocutaneous syndrome