| Costello syndrome: a Ras/mitogen activated protein kinase pathway syndrome (rasopathy) resulting from HRAS germline mutations. | |
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MedLine Citation:
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PMID: 22261753 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Costello syndrome (OMIM# 218040) is a distinctive rare multisystem disorder comprising a characteristic coarse facial appearance, intellectual disabilities, and tumor predisposition. Although the diagnosis can be suspected clinically, confirmation requires identification of a heterozygous mutation in the proto-oncogene HRAS. In contrast to somatic oncogenic mutations in neoplasia, the Costello syndrome changes are typically introduced in the paternal germline. The predicted amino acid substitutions allow for constitutive or prolonged activation of the HRAS protein, resulting in dysregulation of the Ras/mitogen activated protein kinase pathway. Dysregulation of this signaling pathway is the disease mechanism shared among Costello syndrome and other rasopathies, including neurofibromatosis type 1, Noonan syndrome, cardio-facio-cutaneous syndrome, and Legius syndrome. The Ras/mitogen activated protein kinase pathway governs cell proliferation and differentiation, and its dysregulation affects cardiac and brain development, accounting for the significant overlap in physical and developmental differences and common medical problems among rasopathies. Unlike the genetically heterogeneous Noonan syndrome and cardio-facio-cutaneous syndrome, Costello syndrome is caused by HRAS mutations only. Patients, clinicians, and researchers may benefit from a multidisciplinary "rasopathy clinic," which serves patients with more common conditions such as Noonan syndrome and neurofibromatosis and those affected by rare conditions such as Costello syndrome. |
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Authors:
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Karen W Gripp; Angela E Lin |
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Publication Detail:
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Type: Case Reports; Journal Article; Review |
Journal Detail:
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Title: Genetics in medicine : official journal of the American College of Medical Genetics Volume: 14 ISSN: 1530-0366 ISO Abbreviation: Genet. Med. Publication Date: 2012 Mar |
Date Detail:
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Created Date: 2012-03-06 Completed Date: 2012-07-09 Revised Date: 2012-08-16 |
Medline Journal Info:
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Nlm Unique ID: 9815831 Medline TA: Genet Med Country: United States |
Other Details:
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Languages: eng Pagination: 285-92 Citation Subset: IM |
Affiliation:
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Division of Medical Genetics, Alfred I. duPont Hospital for Children, Wilmington, Delaware, USA. kgripp@nemours.org |
| Data Bank Information | |
Bank Name/Acc. No.:
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OMIM/218040 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Alleles Child Costello Syndrome / diagnosis, epidemiology, genetics*, therapy Facies Female Gene Frequency Genetic Association Studies Genetic Predisposition to Disease Germ-Line Mutation* Humans Male Phenotype Prevalence Protein-Serine-Threonine Kinases / genetics Proto-Oncogene Proteins p21(ras) / genetics*, metabolism |
| Chemical | |
Reg. No./Substance:
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EC 2.7.1.-/Mnk1 protein, rat; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 3.6.5.2/Proto-Oncogene Proteins p21(ras) |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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