RASopathies (Noonan, LEOPARD, Costello) [27 genes]

RASopathies are a group of developmental disorders with clinical overlap caused by variants affecting components or modulators of the mitogenic activation protein kinase (MAPK)-dependent signaling pathway.

The best-known syndrome in the spectrum of RASopathies is Noonan syndrome, characterized by the presence of some of the following features: short stature, dysmorphic facial features, cardiac involvement (congenital heart disease and hypertrophic cardiomyopathy), lymphatic disease, learning difficulties / intellectual disability, hemorrhagic diathesis, skeletal malformations and/or predisposition to develop cancer.

Other related syndromes are included in this spectrum, such as cardiofaciocutaneous syndrome, Costello syndrome, Legius syndrome, and Noonan syndrome with multiple lentigines. The genetic characterization of these diseases allows us to confirm the diagnosis, guide treatment (specific in some cases) and follow-up.

The best-known pathology of this group is Noonan syndrome, with an estimated prevalence between 1/1,000 and 1/2,500 newborns.

The genetic study in RASopathies enables differential and etiological diagnosis since there is frequently a clinical overlap between the different conditions of this group of diseases and the study of family members, so that carriers have access to an early / preclinical diagnosis and non-carriers can be safely discharged from cardiology consultations.

Genetic study is indicated in individuals with clinical suspicion of RASopathies (Noonan, LEOPARD, Costello, Legius or cardiofaciocutaneous syndrome).