Document Detail

Noonan syndrome, the Ras-MAPK signalling pathway and short stature.
MedLine Citation:
PMID:  19407499     Owner:  NLM     Status:  MEDLINE    
Short stature, with a mean final height almost two standard deviations below the normal mean, is a major feature of Noonan syndrome. The biological basis of the growth failure is not yet clear. The recent detection of mutations in the protein tyrosine phosphatase, non-receptor type 11 gene (PTPN11) in half of all individuals with Noonan syndrome has opened up a new perspective from the endocrine point of view, since the tyrosine phosphatase SHP2 encoded by PTPN11 is implicated in the downregulation of growth hormone (GH) receptor signalling. Current data show decreased insulin-like growth factor (IGF)-I and IGF-binding protein 3 (IGFBP-3) levels in those children with Noonan syndrome who carry PTPN11 mutations. GH responsiveness seems to be reduced in the presence of PTPN11 mutations, but, so far, data are too scarce to draw any final conclusions. Children with Noonan or Noonan-related syndromes carrying mutations in components of the Ras-mitogen-activated protein kinase (MAPK) signalling pathway downstream from SHP2 also have short stature, though less frequently in the case of SOS1 mutations. Therefore, apart from the disturbance of GH signalling, there must be other relevant mechanisms that influence longitudinal growth in Noonan syndrome. In a small subgroup of patients with Noonan syndrome and Noonan-related syndromes, tumour risk is increased. This susceptibility is relevant when GH therapy is considered. Progress in the understanding of cell regulation by Ras-MAPK signalling and its interconnection with other pathways will hopefully provide evidence on which therapy might be helpful and which might be nocuous in the care of children with Noonan syndrome.
Gerhard Binder
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Publication Detail:
Type:  Journal Article; Review     Date:  2009-04-29
Journal Detail:
Title:  Hormone research     Volume:  71 Suppl 2     ISSN:  1423-0046     ISO Abbreviation:  Horm. Res.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-05-01     Completed Date:  2009-07-23     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0366126     Medline TA:  Horm Res     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  64-70     Citation Subset:  IM    
Copyright Information:
Copyright 2009 S. Karger AG, Basel.
Paediatric Endocrinology, University Children's Hospital, Tubingen, Germany.
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MeSH Terms
Carrier Proteins / genetics,  metabolism*
Down-Regulation / genetics
MAP Kinase Signaling System*
Mitogen-Activated Protein Kinase Kinases / genetics,  metabolism*
Neoplasms / enzymology,  genetics,  therapy
Noonan Syndrome / enzymology*,  genetics,  therapy
Oncogene Protein p21(ras) / genetics,  metabolism*
Protein Tyrosine Phosphatase, Non-Receptor Type 11 / genetics,  metabolism
Risk Factors
Reg. No./Substance:
0/Carrier Proteins; 0/somatotropin-binding protein; EC Protein Kinase Kinases; EC protein, human; EC Tyrosine Phosphatase, Non-Receptor Type 11; EC Protein p21(ras)

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