Cardiofaciocutaneous syndrome (CFC) is a rare genetic disorder classified under the multiple congenital anomalies/mental retardation (MCA/MR) syndromes. The major characteristic of the disease is the distinctive facial appearance, which includes relative macrocephaly, short neck, high and prominent forehead, bitemporal constriction, short nose with depressed nasal bridge, prominent posteriorly angulated pinna, palpebral fissures, ocular hypertelorism, ptosis, and estropia. The patients have unusually sparse, brittle, and curly scalp hair, sparse or absent eyelashes and eyebrows, and display a range of skin abnormalities, ranging from dermatitis and follicular keratosis to hyperpigmentation and generalized ichthyosis. Congenital heart defects, especially valvar pulmonary stenosis and atrial septal defects are common. Affected individuals may show delayed growth, psychomotor retardation, and/or mental retardation.
Mutations in any of the three genes - Mitogen-Activated Protein Kinase Kinase 1 (MAP2K1), Mitogen-Activated Protein Kinase Kinase 2 (MAP2K2), and V-Raf Murine Sarcoma Viral Oncogene Homolog B1 (BRAF) have been shown to cause CFC syndrome. The protein products of these genes are components of the Mitogen Activated Protein Kinase (MAPK) pathway, which is one of the most important molecular mechanisms involved in growth and differentiation.
