Cardiofaciocutaneous syndrome (CFCS) is a rare developmental disorder that is phenotypically similar to Noonan syndrome and is associated with mutations in BRAF, MEK1, MEK2, and KRAS.
Approximately 25% of individuals with CFC have mutations in either MEK1 or MEK2 that lead to increased MEK kinase activity as judged by increased phosphorylation of its downstream effector ERK.
Approximately 25% of individuals with CFC have mutations in either MEK1 or MEK2 that lead to increased MEK kinase activity as judged by increased phosphorylation of its downstream effector ERK.
Approximately 25% of individuals with CFC have mutations in either MEK1 or MEK2 that lead to increased MEK kinase activity as judged by increased phosphorylation of its downstream effector ERK.
Cardio-facio-cutaneous and Noonan syndromes due to mutations in the RAS/MAPK signalling pathway: genotype-phenotype relationships and overlap with Costello syndrome.
Children born with germ-line mutations in BRAF, MEK1 or MEK2 develop cardio-facio-cutaneous (CFC) syndrome, an autosomal dominant syndrome characterized by a distinctive facial appearance, heart defects, skin and hair abnormalities and mental retardation.
Clinical review of known individuals with MEK1/MEK2 mutations suggests that these patients show dysmorphic features, ectodermal abnormalities and cognitive deficit similar to what was observed in BRAF-mutated patients and in the general CFCS population.
In recent years, vertical transmission of CFC has been seen in mutations involving the MEK2 and KRAS genes, but has not previously been reported with BRAF mutations.
Moreover, mutations in several genes associated with the Ras-mitogen-activated protein kinase (MAPK) pathway, including HRAS, BRAF, MEK1, and MEK2 were identified in patients with Costello syndrome and CFC syndrome.