The cardiofaciocutaneous syndrome.
The cardiofaciocutaneous (CFC) syndrome is a condition of sporadic occurrence, with patients showing multiple congenital anomalies and mental retardation. It is characterised by failure to thrive, relative macrocephaly, a distinctive face with prominent forehead, bitemporal constriction, absence of eyebrows, hypertelorism, downward-slanting palpebral fissures often with epicanthic folds, depressed nasal root and a bulbous tip of the nose. The cutaneous involvement consists of dry, hyperkeratotic, scaly skin, sparse and curly hair, and cavernous haemangiomata. Most patients have a congenital heart defect, most commonly pulmonic stenosis and hypertrophic cardiomyopathy. The developmental delay usually is moderate to severe. The syndrome is caused by gain-of-function mutations in four different genes BRAF, KRAS, mitogen-activated protein/extracellular signal-regulated kinase MEK1 and MEK2, all belonging to the same RAS-extracellular signal-regulated kinase (ERK) pathway that regulates cell differentiation, proliferation and apoptosis. The CFC syndrome is a member of a family of syndromes that includes the Noonan and Costello syndromes, presenting with phenotypic similarities. Noonan syndrome is caused by mutations in the protein tyrosine phosphatase SHP-2 gene (PTPN11), with a few people having a mutation in KRAS. Costello syndrome is caused by mutations in HRAS. The protein products of these genes also belong to the RAS-ERK pathway. Thus, the clinical overlap of these three conditions, which often poses a problem of differential diagnosis, is explained by their pathogenetic relatedness.
Roberts
A
A
Harvard Medical School, Partners Healthcare System, Center for Genetics and Genomics, Boston, Massachusetts, USA.
Allanson
J
J
Jadico
S K
SK
Kavamura
M I
MI
Noonan
J
J
Opitz
J M
JM
Young
T
T
Neri
G
G
D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D003937:Diagnosis, Differential; D004065:Digestive System Abnormalities / Q000175:diagnosis; D005124:Eye Abnormalities / Q000175:diagnosis; D019066:Facies; D005260:Female; D005796:Genes; D006330:Heart Defects, Congenital / Q000175:diagnosis*; D006402:Hematologic Diseases / Q000175:diagnosis; D006801:Humans; D008297:Male; D009154:Mutation; D009421:Nervous System Malformations / Q000175:diagnosis; D009634:Noonan Syndrome / Q000175:diagnosis / Q000235:genetics; D012868:Skin Abnormalities / Q000175:diagnosis* / Q000473:pathology; D013577:Syndrome