Dermatological findings in 61 mutation-positive individuals with cardiofaciocutaneous syndrome. Br J Dermatol 2011 Mar;164(3):521-9
Date
11/11/2010Pubmed ID
21062266Pubmed Central ID
PMC4063552DOI
10.1111/j.1365-2133.2010.10122.xScopus ID
2-s2.0-79952429680 (requires institutional sign-in at Scopus site) 78 CitationsAbstract
BACKGROUND: The RASopathies are a class of human genetic syndromes that are caused by germline mutations in genes which encode components of the Ras/mitogen-activated protein kinase (MAPK) pathway. Cardiofaciocutaneous (CFC) syndrome is characterized by distinctive craniofacial features, congenital heart defects, and abnormalities of the skin and hair.
OBJECTIVES: Systematically to characterize the spectrum of dermatological findings in mutation-positive individuals with CFC syndrome.
METHODS: Dermatological surveys were designed by the authors and distributed to the study participants through CFC International or directly by the authors (K.A.R. and D.H.S.) between July 2006 and August 2009. A second follow-up survey was collected between December 2007 and August 2009. When available, digital images and medical records of the participants were obtained. Study participants included individuals with CFC syndrome who have a mutation in BRAF, MAP2K1, MAP2K2 or KRAS.
RESULTS: Individuals with CFC syndrome have a variety of dermatological manifestations caused by dysregulation of the MAPK pathway in development. Numerous acquired melanocytic naevi were one of the most striking features: more than 50 naevi were reported by 23% (14/61) of participants and of those, more than 100 naevi were reported by 36% (5/14). Keratosis pilaris was reported in 80% (49/61) of cases. Ulerythema ophryogenes was common, occurring in 90% (55/61). Infantile haemangiomas occurred at a greater frequency, 26% (16/61), as compared with the general population.
CONCLUSIONS: CFC syndrome has a complex dermatological phenotype with many cutaneous features, some of which allow it to be differentiated from the other Ras/MAPK pathway syndromes. Multiple café-au-lait macules and papillomas were not identified in this CFC cohort, helping to distinguish CFC from other RASopathies such as neurofibromatosis type 1 and Costello syndrome.
Author List
Siegel DH, McKenzie J, Frieden IJ, Rauen KAMESH terms used to index this publication - Major topics in bold
Abnormalities, MultipleAdolescent
Adult
Child
Child, Preschool
Ectodermal Dysplasia
Facies
Failure to Thrive
Female
Germ-Line Mutation
Hair Diseases
Heart Defects, Congenital
Humans
Infant
MAP Kinase Kinase 1
MAP Kinase Kinase 2
Male
Proto-Oncogene Proteins
Proto-Oncogene Proteins B-raf
Proto-Oncogene Proteins p21(ras)
Skin Abnormalities
Young Adult
ras Proteins