The cardiofaciocutaneous syndrome.

Published

Journal Article (Review)

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.

Full Text

Duke Authors

Cited Authors

  • Roberts, A; Allanson, J; Jadico, SK; Kavamura, MI; Noonan, J; Opitz, JM; Young, T; Neri, G

Published Date

  • November 2006

Published In

Volume / Issue

  • 43 / 11

Start / End Page

  • 833 - 842

PubMed ID

  • 16825433

Pubmed Central ID

  • 16825433

Electronic International Standard Serial Number (EISSN)

  • 1468-6244

Digital Object Identifier (DOI)

  • 10.1136/jmg.2006.042796

Language

  • eng

Conference Location

  • England