RASopathies is the term for a clinically and genetically heterogeneous group of disorders that are caused by germline mutations in genes that encode protein components of the Ras/mitogen-activated-protein kinase (MAPK) pathway. The Ras/MAPK pathway plays an essential role in processes crucial for normal development: regulation of the cell cycle, differentiation, growth and apoptosis. Therefore, dysregulation of this pathway has a profound impact on development.
Several organ systems, including the cardiovascular system, are affected. The syndromes overlap significantly in their signs and symptoms, which may complicate establishing a clear diagnosis and targeted diagnostic procedures. Moreover, several of these disorders may be caused by pathogenic changes in various genes of the Ras/MAPK pathway, most of which are activating changes which increase signal transduction within this pathway.
Rauen 2013, Annu Rev Genomics Hum Genet. 14:355-369