title: Genetic and pathogenetic aspects of Noonan syndrome and related disorders.
abstract: Noonan syndrome (NS) and the clinically overlapping disorders cardio-facio-cutaneous syndrome, LEOPARD syndrome, Costello syndrome and Neurofibromatosis-Noonan syndrome share the clinical features of short stature, the same spectrum of congenital heart defects, and a similar pattern of craniofacial anomalies. It is now known that all these disorders are caused by mutations in components of the RAS-MAPK signaling pathway. This pathway was previously known for its involvement in tumorigenesis. This article reviews the current knowledge on underlying genetic alterations and possible pathogenetic mechanisms responsible for NS and related disorders. It discusses the relationship between a group of developmental disorders and oncogenes. Potential future treatment prospects are based on the possibility of inhibiting RAS-MAPK signaling by pharmaceuticals.
authors.affiliation: Institute of Human Genetics, University Hospital Erlangen, University of Erlangen-Nuremberg, Germany. martin.zenker@med.ovgu.de
authors.forename: Martin
authors.initials: M
authors.lastname: Zenker
mesh_terms: D001827:Body Height; D056685:Costello Syndrome / Q000235:genetics / Q000503:physiopathology; D005260:Female; D006130:Growth Disorders / Q000235:genetics; D006330:Heart Defects, Congenital / Q000235:genetics; D006801:Humans; D044542:LEOPARD Syndrome / Q000235:genetics / Q000503:physiopathology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics; D009154:Mutation; D017253:Neurofibromatoses / Q000235:genetics / Q000503:physiopathology; D009634:Noonan Syndrome / Q000235:genetics* / Q000503:physiopathology*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D020837:SOS1 Protein / Q000235:genetics; D015398:Signal Transduction
chemical_list: D020837:SOS1 Protein; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020928:Mitogen-Activated Protein Kinases; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D016283:Proto-Oncogene Proteins p21(ras)