Costello syndrome and related disorders
Emilio Quezada1, Karen W Gripp
1Division of Medical Genetics, A.I. duPont Hospital for Children, Wilmington, Delaware 19803, USA.
Current Opinion in Pediatrics
|November 21, 2007
Summary
Costello syndrome, a rare genetic disorder, is caused by HRAS gene mutations leading to overactive Ras-MAPK signaling. Molecular testing confirms diagnosis and distinguishes it from similar conditions like cardio-facio-cutaneous syndrome.
Area of Science:
- Genetics
- Molecular Biology
- Pediatric Medicine
Background:
- Costello syndrome is a rare congenital disorder with multi-systemic effects, including failure to thrive, cardiac issues, and cognitive impairment.
- It shares clinical features with cardio-facio-cutaneous syndrome, making diagnosis challenging.
- Genetic discoveries are crucial for molecularly confirming diagnoses of these related disorders.
Purpose of the Study:
- To review the genetic basis of Costello syndrome and related disorders.
- To explain the molecular mechanisms underlying shared phenotypic findings.
- To highlight the role of molecular testing in diagnosis.
Main Methods:
- Review of scientific literature on Costello syndrome and related RASopathies.
- Analysis of genetic mutations identified in affected individuals.
- Correlation of genotype with clinical phenotype.
Main Results:
- Germline HRAS mutations are identified in Costello syndrome.
- Mutations in BRAF, MEK1, and MEK2 are linked to cardio-facio-cutaneous syndrome.
- These mutations affect the Ras-mitogen-activated protein kinase (MAPK) pathway, explaining shared features.
Conclusions:
- Costello syndrome results from HRAS mutations causing increased MAPK pathway activation.
- Despite overlapping symptoms, Costello syndrome and related disorders are distinct, with phenotypes diverging with age.
- Molecular testing is essential for accurate diagnosis and should guide clinical assessment.
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