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Review
. 2013 Jan 26;381(9863):333-42.
doi: 10.1016/S0140-6736(12)61023-X. Epub 2013 Jan 10.

Noonan syndrome

Amy E Roberts  1 , Judith E Allanson, Marco Tartaglia, Bruce D Gelb
Affiliations
Review

Noonan syndrome

Amy E Roberts et al. Lancet. .

Abstract

Noonan syndrome is a genetic multisystem disorder characterised by distinctive facial features, developmental delay, learning difficulties, short stature, congenital heart disease, renal anomalies, lymphatic malformations, and bleeding difficulties. Mutations that cause Noonan syndrome alter genes encoding proteins with roles in the RAS-MAPK pathway, leading to pathway dysregulation. Management guidelines have been developed. Several clinically relevant genotype-phenotype correlations aid risk assessment and patient management. Increased understanding of the pathophysiology of the disease could help development of pharmacogenetic treatments.

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Conflict of interest statement

Conflicts of interest

BDG and MT have received royalties for genetic testing for Noonan syndrome from the following: GeneDx, Prevention Genetics, Correlagen, Harvard/Partners, and Baylor College of Medicine. AER and JEA declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1. The RAS–MAPK signaling pathway
Growth signals are relayed from activated growth factor receptors to the nucleus. Mutations in PTPN11, KRAS, SOS, NRAS, and RAF1 are associated with Noonan syndrome and mutations in SHOC2 and CBL are associated with a Noonan syndrome-like phenotype.
Figure 2
Figure 2. Five generations of a family with Noonan syndrome caused by an SOS1 mutation
Distinguishing facial features become milder with age.
See this image and copyright information in PMC

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