Document Detail


Costello syndrome and related disorders.
MedLine Citation:
PMID:  18025929     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Emilio Quezada; Karen W Gripp
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Current opinion in pediatrics     Volume:  19     ISSN:  1040-8703     ISO Abbreviation:  Curr. Opin. Pediatr.     Publication Date:  2007 Dec 
Date Detail:
Created Date:  2007-11-20     Completed Date:  2008-02-25     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9000850     Medline TA:  Curr Opin Pediatr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  636-44     Citation Subset:  IM    
Affiliation:
Division of Medical Genetics, A.I. duPont Hospital for Children, Wilmington, Delaware 19803, USA.
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MeSH Terms
Descriptor/Qualifier:
Abnormalities, Multiple / 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:
0/KRAS protein, human; 0/Proto-Oncogene Proteins; EC 3.6.5.2/ras Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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