RASopathy-associated Cardiomyopathy

RASopathies are a family of developmental disorders that share germline mutations in the components of the RAS-MAPK pathway leading to dysregulated signalling. A high prevalence of hypertrophic cardiomyopathy (HCM) in these patients suggested genetic involvement. Whether RASopathies are an aetiology of HCM or a comorbidity with ominous prognostic implications remained a debatable issue for sometimes in the past. However, recent evidence demonstrates RASopathies can result in a specific form of cardiomyopathy (CM), particularly in the paediatric population. Although this type of CM shares many pathologic cardiac manifestations with HCM, it is a more severe form with significantly higher mortality rates. Same to other genetic diseases, RASopathies have a very low prevalence, and hence, neglected in pathophysiological research. Consequently, pathogenic mechanisms of RASopathy-associated CM remains unclear and lacks aetiological treatment. Clinical overlap between RASopathy phenotypes, extensive cardiac variability within each phenotype and within families, and between unrelated individuals with the sane genetic mutation has complicated diagnosis and treatment. Thus, the understanding of RASopathy-associated CM and accurate diagnosis is essential to guide the choice of the most appropriate treatment. This paper reviews published evidence on RASopathy-associated CM with a focus on its phenotypic expression, pathogenesis, clinical evaluation and management.