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PMID: 21396583 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Noonan syndrome and clinically related disorders.

Best practice & research. Clinical endocrinology & metabolism ·Vol. 25 ·No. 1 ·2011-02-00 ·Pages 161-79

Tartaglia M, Gelb BD, Zenker M

Abstract

Noonan syndrome is a relatively common, clinically variable developmental disorder. Cardinal features include postnatally reduced growth, distinctive facial dysmorphism, congenital heart defects and hypertrophic cardiomyopathy, variable cognitive deficit and skeletal, ectodermal and hematologic anomalies. Noonan syndrome is transmitted as an autosomal dominant trait, and is genetically heterogeneous. So far, heterozygous mutations in nine genes (PTPN11, SOS1, KRAS, NRAS, RAF1, BRAF, SHOC2, MEK1 and CBL) have been documented to underlie this disorder or clinically related phenotypes. Based on these recent discoveries, the diagnosis can now be confirmed molecularly in approximately 75% of affected individuals. Affected genes encode for proteins participating in the RAS-mitogen-activated protein kinases (MAPK) signal transduction pathway, which is implicated in several developmental processes controlling morphology determination, organogenesis, synaptic plasticity and growth. Here, we provide an overview of clinical aspects of this disorder and closely related conditions, the molecular mechanisms underlying pathogenesis, and major genotype-phenotype correlations.

MeSH Terms
Adolescent Child Costello Syndrome/diagnosis,genetics Ectodermal Dysplasia/diagnosis,genetics Facies Failure to Thrive/diagnosis,genetics Heart Defects, Congenital/diagnosis,genetics Humans Infant Intracellular Signaling Peptides and Proteins/genetics LEOPARD Syndrome/diagnosis,genetics Loose Anagen Hair Syndrome/diagnosis,genetics Mitogen-Activated Protein Kinases/genetics Neurofibromatosis 1/genetics Noonan Syndrome/diagnosis,genetics Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics Proto-Oncogene Proteins B-raf/genetics Proto-Oncogene Proteins c-cbl/genetics Proto-Oncogene Proteins c-raf/genetics SOS1 Protein/genetics
Chemicals
Intracellular Signaling Peptides and Proteins SHOC2 protein, human SOS1 Protein Proto-Oncogene Proteins c-cbl BRAF protein, human Proto-Oncogene Proteins B-raf Proto-Oncogene Proteins c-raf Mitogen-Activated Protein Kinases PTPN11 protein, human Protein Tyrosine Phosphatase, Non-Receptor Type 11 CBL protein, human
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Tartaglia Marco
Dipartimento di Ematologia, Oncologia e Medicina Molecolare, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome, Italy. [email protected]
Gelb Bruce D
Zenker Martin
Supplementary Concepts
Cardiofaciocutaneous syndrome (Disease)
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Article Info
Journal
Best practice & research. Clinical endocrinology & metabolism
Abbr.
Best Pract Res Clin Endocrinol Metab
ISSN
1878-1594
DOI
10.1016/j.beem.2010.09.002
Email
[email protected]
Published
2011-02-00
Pages
161-79
Language
English
Region
Netherlands
NLM ID
101120682
PMCID
PMC3058199
Subset
IM
Grants
Telethon · GGP10020 · Italy
NHLBI NIH HHS · R01 HL071207 · United States
NHLBI NIH HHS · R01 HL071207-09 · United States
NHLBI NIH HHS · HL71207 · United States
External Links
PubMed source DOI: 10.1016/j.beem.2010.09.002 PMC Full Text
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