RASopathies and cardiac manifestations

As binary switches, RAS proteins switch to an ON/OFF state during signaling and are on a leash under normal conditions. However, in RAS-related diseases such as cancer RASopathies, mutations the genes that regulate or itself permanently activate protein. The structural basis of this is well understood; however, exact mechanisms by which regulated less clear. RAS/MAPK syndromes multisystem developmental disorders caused germline associated with RAS/mitogen-activated protein kinase pathway, impacting 1 1,000–2,500 children. These include variety Noonan syndrome (NS) NS-related (NSRD), cardio facio cutaneous (CFC) syndrome, Costello (CS), NS multiple lentigines (NSML, also known LEOPARD syndrome). A frequent manifestation cardiomyopathy (CM) hypertrophic RASopathies suggest could be potential causative factor for CM. current supporting evidence sporadic unclear. RASopathy-patients display broad spectrum congenital heart disease (CHD). More than 15 encode components pathway essential cell cycle play regulatory roles proliferation, differentiation, growth, metabolism. linked molecular genetic pathogenesis these syndromes. heterogeneity given one hand alleles other make classification difficult diagnosing RAS/MAPK-related diseases. Although there some homogeneity most several allelic This allelism points role critical nodes sheds light overlap between related Even though considerable progress has been made understanding pathophysiology RASopathy identification causal functional analysis their pathophysiological consequences, still unidentified many patients diagnosed RASopathies.