Molecular causes of the cardio-facio-cutaneous syndrome

W. E. Tidyman, Katherine A Rauen

Research output: Chapter in Book/Report/Conference proceedingChapter

9 Scopus citations


Cardio-facio-cutaneous (CFC) syndrome is a rare multiple congenital anomaly disorder in which individuals have characteristic dysmorphic craniofacial features, cardiac defects, ectodermal anomalies, developmental delay and hypotonia. CFC is caused by alteration of activity through the mitogen-activated protein kinase (MAPK) pathway due to heterozygous de novo mutations in protein kinases B-Raf, MEK1 or MEK2. Mutations in K-Ras, a small GTPase, have also been implicated as causing CFC syndrome and Noonan syndrome, however its role has yet to be well defined. In those individuals who are found to have a mutation, the majority occur in BRAF, whereas, mutations in MEK1 or MEK2 comprise about 27%. Functional studies of these novel CFC mutant proteins demonstrate that B-Raf may be activated or kinase impaired, whereas all the MEK mutant proteins studied to date demonstrate increased activity. Since CFC syndrome may have a progressive, evolving phenotype, the possible use of systemic therapies to reduce MAPK activity may be of great benefit to this population of patients and certainly warrants investigation. However, animal studies on the effects of MAPK inhibitors will be essential because of the critical role this pathway plays during development.

Original languageEnglish (US)
Title of host publicationNoonan Syndrome and Related Disorders - A Matter of Deregulated Ras Signaling
Number of pages10
StatePublished - 2009

Publication series

NameMonographs in Human Genetics
ISSN (Print)00770876
ISSN (Electronic)16623835

ASJC Scopus subject areas

  • Genetics(clinical)


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