| Costello syndrome and related disorders. | |
MedLine Citation:
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PMID: 18025929 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE OF REVIEW: Costello syndrome is a rare congenital disorder affecting multiple organ systems, encompassing severe failure to thrive, cardiac anomalies including hypertrophic cardiomyopathy and atrial tachycardia, tumor predisposition, and cognitive impairment. Costello syndrome shares findings with cardio-facio-cutaneous syndrome and the diagnosis can be challenging. The discovery of gene mutations underlying these and other closely related disorders allows for molecular confirmation of a clinical diagnosis. RECENT FINDINGS: The identification of germline HRAS mutations in Costello syndrome, and mutations in BRAF, MEK1 and MEK2 in cardio-facio-cutaneous syndrome, uncovered the biologic mechanism for the shared phenotypic findings based on the close interaction of the gene products within the Ras-mitogen-activated protein kinase pathway. Changes in other genes encoding mitogen-activated protein kinase pathway proteins are responsible for Noonan syndrome and the KRAS mutation phenotype. SUMMARY: Costello syndrome is caused by heterozygous de-novo point mutations in HRAS, resulting in increased activation of the mitogen-activated protein kinase pathway. Despite their overlapping presentation, Costello syndrome and its related disorders are distinct, and the phenotypes become more distinctive with age. Molecular testing is available and a clinical diagnosis should be reconsidered if it is inconsistent with the molecular result. |
Authors:
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Emilio Quezada; Karen W Gripp |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Current opinion in pediatrics Volume: 19 ISSN: 1040-8703 ISO Abbreviation: Curr. Opin. Pediatr. Publication Date: 2007 Dec |
Date Detail:
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Created Date: 2007-11-20 Completed Date: 2008-02-25 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9000850 Medline TA: Curr Opin Pediatr Country: United States |
Other Details:
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Languages: eng Pagination: 636-44 Citation Subset: IM |
Affiliation:
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Division of Medical Genetics, A.I. duPont Hospital for Children, Wilmington, Delaware 19803, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Abnormalities, Multiple
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genetics* Child Developmental Disabilities / genetics Diagnosis, Differential Face / abnormalities* Facies Genes, ras / genetics Genetic Predisposition to Disease Genotype Germ-Line Mutation Heart Diseases / genetics* Humans LEOPARD Syndrome / genetics MAP Kinase Signaling System / genetics Mental Retardation / genetics Neoplasms / genetics Neurofibromatosis 1 / genetics Noonan Syndrome / genetics Phenotype Proto-Oncogene Proteins / genetics Rhabdomyosarcoma / genetics Skin Abnormalities / diagnosis, genetics Syndrome ras Proteins / genetics |
| Chemical | |
Reg. No./Substance:
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0/KRAS protein, human; 0/Proto-Oncogene Proteins; EC 3.6.5.2/ras Proteins |
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