Cardio-Facio-Cutaneous Syndrome: Phenotypic Variability and Differential Diagnosis in 3 Cases with de novo BRAF Mutations

Abstract

Cardio-facio-cutaneous (CFC) syndrome is a developmental disorder causing mental retardation and multiple congenital anomalies, including craniofacial, ectodermal, cardiac and musculoskeletal defects. Mutation of several genes in the RAS/MAPK (mitogen activated protein kinase) signaling pathway, most commonly BRAF, results in CFC syndrome. In this study, we report 3 new patients with CFC syndrome caused by mutation of BRAF. These patients differed in neurological impairment, craniofacial features and cardiac defects, while they shared relatively similar ectodermal and skeletal anomalies. They also displayed some overlapping features with Costello syndrome, another RAS/MAPK pathway disorder. Our findings highlight the clinical variability of CFC syndrome, with respect to severity and pattern of the affected organs, as well as the phenotypic overlap with the Costello syndrome.

Key words

cardio-facio-cutaneous syndrome - phenotypic variability - BRAF mutation - differential diagnosis

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