Scientific Background
Approximately 100 patients with cardiofaciocutaneous syndrome (CFC) have been documented in literature so far. It is assumed that there are 200 to 300 affected patients worldwide, although the disease is underdiagnosed. In this disease, which belongs to the group of RASopathies, the diagnostic differentiation from other syndromes of the spectrum during infancy and toddlerhood is difficult due to the phenotypic similarity. The diagnosis is usually confirmed on a molecular genetic level.
Characteristics such as failure to thrive, developmental delay and growth retardation, facial dysmorphia (eyelids slope outward and downward, hypertelorism, high forehead), changes in pigmentation, anomalies of the gastrointestinal tract and central nervous system, heart defects, and thoracic deformities may be accompanied by ectodermal involvement in the form of thin hair and nail hypoplasia. In adulthood, dry, hyperkeratotic skin with additional palmoplantar hyperkeratosis becomes apparent. An increased predisposition for malignant diseases has not yet been reported.
Cardiofaciocutaneous syndrome is genetically heterogeneous. Pathogenic variants in the genes BRAF, KRAS, MAP2K1 and MAP2K2 can cause CFC.
References
Grant et al. 2018 Hum Mut doi: 10.1002/humu.23624 / Templin et al. 2016, Am J Med Genet A.; 170A:441 / Roberts et al. 2013, The Lancet 381:333 / Rodriguez-Viciana et al. 2006, Science 311:1287 / Niihori et al. 2006, Nat Genet 38:294 / Tartaglia et al. 2003, Clin Genet 63:423