日本小児循環器学会雑誌 Pediatric Cardiology and Cardiac Surgery

RAS/mitogen activated protein kinase (MAPK) pathway dysregulation, triggered by germline mutations in the involved genes, leads to a congenital syndrome termed “RASopathy.” Each form of RASopathy expresses a unique clinical phenotype; however, they share a series of functional and morphological organ abnormalities, including cardiac malformations, specific facial features, skeletal abnormalities, and intellectual disabilities. Secondary hypertrophic cardiomyopathy is the characteristic cardiac phenotype of RASopathy; its presence is strongly associated with heart failure-related mortality and sudden death. Therefore, RASopathy-associated hypertrophic cardiomyopathy (RAS-CMP) is a disease of priority in pediatric cardiology. However, the complete picture of its pathogenesis remains to be elucidated. Along with the development of novel molecular therapeutics, improving the quality of RASopathy care through collaborations between basic research and clinical practice is significantly needed. This review aimed to introduce the current evidence surrounding RAS-CMP and outline the knowledge gaps that should be addressed. Moreover, from the viewpoint of biological analogies between RAS/MAPK-related cancers and RASopathies, we deepen our discussion of recently emerging clues for exploring novel therapeutic approaches to RASopathy care.