Cardio-Facio-Cutaneous Syndrome

Cardio-facio-cutaneous syndrome (CFC) is an autosomal dominant RASopathy caused by pathogenic variants of genes that encode components of the mitogen-activated protein kinase (MAPK) pathway downstream of RAS. Heterozygous mutations in four genes have been associated with CFC syndrome: BRAF, MAP2K1, MAP2K2, and KRAS. The role of the gene YWHAZ is still under investigation. The RAS/MAPK pathway plays an essential role in the regulation of proliferation, growth, differentiation, cell cycle progression, and cell senescence, all of which are vital to normal human growth and development. The classical phenotypic features associated with CFC syndrome include characteristic facies, cardiac anomalies, ectodermal, gastrointestinal, ocular, musculoskeletal and lymphatic abnormalities, neurologic and behavior issues, including seizures and cognitive delay. Because the RAS/MAPK pathway has been studied intensively in the context of cancer, therapeutics exist that specifically target the pathway which may be of benefit in the treatment of CFC.