Cardiofaciocutaneous (CFC) Syndrome

Ellen Denayer, Department of Human Genetics, Catholic University of Leuven, Leuven, Belgium
Eric Legius, Department of Human Genetics, Catholic University of Leuven, Leuven, Belgium

Published online: September 2011

DOI: 10.1002/9780470015902.a0021470

Cardiofaciocutaneous (CFC) syndrome is a rare genetic disorder that is characterised by facial dysmorphism, cardiac defects, mental retardation, typical ectodermal abnormalities and short stature. It is caused by germline mutations in BRAF, MEK1, MEK2 or KRAS and shows phenotypical overlap with other conditions caused by mutations in the RAS-MAPK pathway such as neurofibromatosis type 1, Noonan, LEOPARD, Costello and Legius syndromes. The identification of the underlying genetic defect opens new windows for therapeutic strategies in these RASopathies including CFC syndrome.

Key Concepts:

  • Mutations in genes coding for key components of the RAS-MAPK pathway are responsible for a group of inherited disorders (RASopathies).
  • The RASopathies are clinically and molecularly related disorders characterised by variable cognitive deficits, growth retardation, facial dysmorphy, and congenital cardiopathies.
  • CFC syndrome is characterised by the most severe intellectual disabilities seen in the RASopathies.
  • Correcting cerebral RAS-MAPK signalling is a potential targeted treatment for learning disabilities in patients with a RASopathy.

Keywords: CFC syndrome; RASopathies; BRAF; MEK; KRAS

Figure 1. The RASopathies. The RAS-MAPK pathway. Proteins associated with RASopathies are shaded in grey, proteins associated with CFC syndrome are shaded in black. The different Rasopathies are shown: Noonan syndrome, LEOPARD syndrome, CFC syndrome, Costello syndrome, Loh syndrome, Legius syndrome, CM-AVM syndrome (capillairy malformation – arteriovenous malformation). For each inherited disorder the associated proteins are indicated. Neurofibromin, P120GAP and SPRED1 are negative regulators of the pathway, whereas the other proteins activate signal transduction through the pathway. The RAS protein is activated by exchanging GDP for GTP. The RAF, MEK and ERK proteins are kinases that are activated by phosphorylation.
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Related Sub-Topics:

Developmental Disorders | Specific Genetic Disorders | Mutational Mechanisms of Genetic Disease
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Article Title: Cardiofaciocutaneous (CFC) Syndrome
 
How to Cite close
Denayer, Ellen, and Legius, Eric(Sep 2011) Cardiofaciocutaneous (CFC) Syndrome. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0021470]