J Genet Med.  2019 Jun;16(1):1-9. 10.5734/JGM.2019.16.1.1.

Noonan syndrome and RASopathies: Clinical features, diagnosis and management

Affiliations
  • 1Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea. hwyoo@amc.seoul.kr
  • 2Genome Research Center for Birth Defects and Genetic Disorders, Medical Genetics Center, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.

Abstract

Noonan syndrome (NS) and NS-related disorders (cardio-facio-cutaneous syndrome, Costello syndrome, NS with multiple lentigines, or LEOPARD [lentigines, ECG conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormal genitalia, retardation of growth and sensory neural deafness] syndrome) are collectively named as RASopathies. Clinical presentations are similar, featured with typical facial features, short stature, intellectual disability, ectodermal abnormalities, congenital heart diseases, chest & skeletal deformity and delayed puberty. During past decades, molecular etiologies of RASopathies have been growingly discovered. The functional perturbations of the RAS-mitogen-activated protein kinase pathway are resulted from the mutation of more than 20 genes (PTPN11, SOS1, RAF1, SHOC2, BRAF, KRAS, NRAS, HRAS, MEK1, MEK2, CBL, SOS2, RIT, RRAS, RASA2, SPRY1, LZTR1, MAP3K8, MYST4, A2ML1, RRAS2). The PTPN11 (40–50%), SOS1 (10–20%), RAF1 (3–17%), and RIT1 (5–9%) mutations are common in NS patients. In this review, the constellation of overlapping clinical features of RASopathies will be described based on genotype as well as their differential diagnostic points and management.

Keyword

Noonan syndrome; Noonan syndrome related disorders; Genes
Full Text Links
  • JGM
Share
  • Twitter
  • Facebook
Copyright © 2020 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr