title: Cardiomyopathies in Noonan syndrome and the other RASopathies.
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.
authors.affiliation: Mindich Child Health and Development Institute, Departments of Pediatrics and Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Gelb
authors.affiliation: Department of Cardiology and Division of Genetics, Boston Children's Hospital, Boston, MA.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Roberts
authors.affiliation: Dipartimento di Ematologia, Oncologia e Medicina Molecolare, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Tartaglia