{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:54:58Z","timestamp":1790913298196,"version":"4.1.0"},"reference-count":66,"publisher":"BMJ","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2006,11]]},"abstract":"<jats:p>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 <jats:italic>BRAF<\/jats:italic>, <jats:italic>KRAS<\/jats:italic>, mitogen-activated protein\/extracellular signal-regulated kinase <jats:italic>MEK<\/jats:italic>\n                  <jats:italic>1<\/jats:italic> and <jats:italic>MEK2<\/jats:italic>, all belonging to the same RAS\u2013extracellular 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 (<jats:italic>PTPN11<\/jats:italic>), with a few people having a mutation in <jats:italic>KRAS<\/jats:italic>. Costello syndrome is caused by mutations in <jats:italic>HRAS<\/jats:italic>. The protein products of these genes also belong to the RAS\u2013ERK pathway. Thus, the clinical overlap of these three conditions, which often poses a problem of differential diagnosis, is explained by their pathogenetic relatedness.<\/jats:p>","DOI":"10.1136\/jmg.2006.042796","type":"journal-article","created":{"date-parts":[[2006,7,6]],"date-time":"2006-07-06T20:34:20Z","timestamp":1152218060000},"page":"833-842","source":"Crossref","is-referenced-by-count":203,"title":["The cardiofaciocutaneous syndrome"],"prefix":"10.1136","volume":"43","author":[{"given":"A","family":"Roberts","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Allanson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S K","family":"Jadico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M 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