The cardiofaciocutaneous syndrome

Abstract

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-offunction 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.Univ Sacred Heart, Inst Med Genet, Fac Med, I-00168 Rome, ItalyDuke Univ, Med Ctr, Dept Ophthalmol, Durham, NC 27705 USADuke Univ, Med Ctr, Dept Pediat, Durham, NC 27705 USAUniv Utah, Sch Med, Dept Pediat, Salt Lake City, UT USAUniv Kentucky, Dept Pediat, Lexington, KY USAUniversidade Federal de São Paulo, São Paulo, BrazilUniv Penn, Sch Med, Philadelphia, PA 19104 USAUniv Ottawa, Ottawa, ON, CanadaChildrens Hosp Eastern Ontario, Ottawa, ON K1H 8L1, CanadaHarvard Univ, Sch Med, Partners Healthcare Syst, Ctr Genet & Genom, Boston, MA 02115 USAUniversidade Federal de São Paulo, EPM, São Paulo, BrazilWeb of Scienc