RASopathy studies (metabolic, cardiovascular, neurological) focusing on personalised, innovative approach toward those rare diseases.

Cardiofaciocutaneous syndrome (CFC) is a rare developmental disorder within the group of RASopathies—conditions caused by germline mutations that dysregulate the Ras/MAPK signaling cascade, a pathway central to cell growth, differentiation, and survival. CFC is associated with pathogenic variants in the BRAF, KRAS, MAP2K1, and MAP2K2 genes.

Clinically, CFC is characterized by distinctive craniofacial features and ectodermal anomalies, including abnormal hair texture, facial dysmorphism, growth retardation, and feeding difficulties. In addition, congenital heart defects, developmental delay, and hypotonia are common, with the severity and frequency of manifestations varying across genetic subtypes.

The growing potential for pathway-targeted therapies, including the increasing reported use of MEK inhibitors for severe cardiac and lymphatic manifestations of RASopathies, underscores the importance of accurate diagnosis and of clearly defining natural history and clinically meaningful treatment endpoints. Further refinement of genotype–phenotype correlations and expansion of the phenotypic spectrum—particularly the systematic delineation of neurological manifestations using clinical and radiographic approaches—are expected to be major areas of progress in the coming years.

Driven by active patient involvement, data registries and biobanks are being established. The MEK2 Research Foundation is securing additional resources to facilitate further investigations using patient-derived cellular models and animal models, enabling translational research aimed at therapy development.