Cardiomyopathies in Noonan syndrome and the other RASopathies. Issue 1 (July 2015)

• Record Type: Journal Article
• Authors: Gelb, Bruce D.; Roberts, Amy E.; Tartaglia, Marco
• Is Part Of: Progress in pediatric cardiology. Volume 39:Issue 1(2015)
• Page Start: 13
• Page End: 19
• Publication Date: 2015-07
• Subjects: RAS/MAP kinase signal transduction -- Hypertrophic cardiomyopathy -- RASopathies -- Dilated cardiomyopathy; Pediatric cardiology -- Periodicals; Cardiovascular Diseases -- Periodicals; Infant; Child; Cardiologie pédiatrique -- Périodiques; 618.9212005
• DOI: 10.1016/j.ppedcard.2015.01.002
• Languages: English
• ISSNs: 1058-9813

Abstract

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.