Cardiomyopathies in Noonan syndrome and the other RASopathies
Bruce D Gelb, Amy E Roberts, Marco Tartaglia, Bruce D Gelb, Amy E Roberts, Marco Tartaglia
Abstract
Noonan syndrome and related disorders (Noonan syndrome with multiple lentigines, Costello syndrome, cardiofaciocutaneous syndrome, Noonan syndrome with loose anagen hair, and other related traits) are autosomal dominant traits. Mutations causing these disorders alter proteins relevant for signaling through RAS. Thus, these traits are now collectively called the RASopathies. While the RASopathies have pleiomorphic features, this review will focus on the hypertrophic cardiomyopathy observed in varying percentages of all of these traits. In addition, inherited abnormalities in one pathway gene, RAF1, cause pediatric-onset dilated cardiomyopathy. The pathogeneses for the RASopathy-associated cardiomyopathies are being elucidated, principally using animal models, leading to genotype-specific insights into how signal transduction is perturbed. Based on those findings, small molecule therapies seem possible for RASopathy-associated cardiomyopathies.
Conflict of interest statement
Conflicts of Interest:
The authors (B.D.G. and M.T.) declare the following conflicts of interest: they receive royalty payments for genetic testing for Noonan syndrome from Correlegan, LabCorp, GeneDx, Prevention Genetics, Baylor College of Medicine, and Harvard/Partners; B.D.G. received a sponsored-research award from Shire.
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Source: PubMed