Cardio-facio-cutaneous syndrome: clinical features, diagnosis, and management guidelines

Abstract

Cardio-facio-cutaneous syndrome (CFC) is one of the RASopathies that bears many clinical features in common with the other syndromes in this group, most notably Noonan syndrome and Costello syndrome. CFC is genetically heterogeneous and caused by gene mutations in the Ras/mitogen-activated protein kinase pathway. The major features of CFC include characteristic craniofacial dysmorphology, congenital heart disease, dermatologic abnormalities, growth retardation, and intellectual disability. It is essential that this condition be differentiated from other RASopathies, as a correct diagnosis is important for appropriate medical management and determining recurrence risk. Children and adults with CFC require multidisciplinary care from specialists, and the need for comprehensive management has been apparent to families and health care professionals caring for affected individuals. To address this need, CFC International, a nonprofit family support organization that provides a forum for information, support, and facilitation of research in basic medical and social issues affecting individuals with CFC, organized a consensus conference. Experts in multiple medical specialties provided clinical management guidelines for pediatricians and other care providers. These guidelines will assist in an accurate diagnosis of individuals with CFC, provide best practice recommendations, and facilitate long-term medical care.

Keywords: BRAF mutation; MEK1 mutation; MEK2 mutation; RASopathy; cardio-facio-cutaneous syndrome; management guidelines.

FIGURE 1

A, Patient with CFC (BRAF p.Q257R missense mutation) at (from left to right) 4 days, 3 months, 3 years, 5 years, 7 years, 12 years, 14 years, and 16 years. B, Patient with CFC (MEK2 p.F57C missense mutation) at (from left to right) 1 day, 3 years, 7 years, 9 years, 13 years, 14 years, 16 years, and 20 years.