Figure 1

Schematic representation of RAS pathway and its correlation with RASopathies, A growth factor activates its RTK causing phosphorylation of tyrosines, which are bound by adapter proteins, SHC/GRB2 and GAB. These interact with the activators of RAS, SOS1 and SHP2, and induce the dissociation of GDP and binding of GTP. RAS-GTP activates a cascade of downstream kinases: the MAPK pathway. On the other hand, the inhibition of RAS signaling is mediated by GAPs: RASA1 and neurofibromin 1. The RASopathies are developmental pathologies due to mutations on genes encoding proteins of the RAS pathway. HCM is uncommon in NS and CFC patients. However, nearly all NS patients with mutated RAF1 develop HCM. PTPN11 (encoding SHP2) loss-of-function mutations were observed in the majority of LS patients who developed HCM. Mutations in RAF1 have also been identified in a small percentage of LS with HCM. CS patients harboring HRAS mutations consistently show cardiac hypertrophy. Light gray shading indicates the mutation-specific syndromes accompanied by HCM; dark gray shading indicates those syndromes in which cardiac hypertrophy is less common.