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PMID: 18382419 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Mechanisms of disease: molecular genetics of arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Nature clinical practice. Cardiovascular medicine ·Vol. 5 ·No. 5 ·2008-05-00 ·Pages 258-67

Awad MM, Calkins H, Judge DP

Abstract

Arrhythmogenic right ventricular dysplasia/cardiomyopathy is an inherited cardiomyopathy estimated to affect approximately 1 in 5,000 individuals. Cardinal manifestations include right ventricular enlargement and dysfunction, fibrofatty replacement of myocytes in the right ventricle, characteristic electrocardiographic abnormalities, and ventricular arrhythmia most commonly arising from the right ventricle. The disease is frequently familial and typically involves autosomal dominant transmission with low penetrance and variable expressivity. Approximately 50% of symptomatic individuals harbor a mutation in one of the five major components of the cardiac desmosome. Nevertheless, other genetic modifiers and environmental factors complicate the clinical management of mutation carriers as well as counseling of their relatives. This Review summarizes the known genetic mutations associated with arrhythmogenic right ventricular dysplasia/cardiomyopathy, describes possible origins of recurrent mutations, presents theories on the pathogenesis of disease following a mutation, and discusses the current issues surrounding clinical use of genetic analysis in the assessment of individuals with this condition.

MeSH Terms
Arrhythmogenic Right Ventricular Dysplasia/diagnosis,genetics,pathology,physiopathology Desmocollins/genetics Desmoglein 2/genetics Desmoplakins/genetics Genetic Predisposition to Disease Genetic Testing Humans Mutation Myocardium/pathology Plakophilins/genetics Risk Factors Ventricular Function, Right gamma Catenin
Chemicals
DSC2 protein, human DSG2 protein, human DSP protein, human Desmocollins Desmoglein 2 Desmoplakins JUP protein, human PKP2 protein, human Plakophilins gamma Catenin
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Awad Mark M
Johns Hopkins University School of Medicine and Johns Hopkins University Cellular and Molecular Medicine Program, Baltimore, MD, USA.
Calkins Hugh
Judge Daniel P
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Article Info
Journal
Nature clinical practice. Cardiovascular medicine
Abbr.
Nat Clin Pract Cardiovasc Med
ISSN
1743-4300
DOI
10.1038/ncpcardio1182
Published
2008-05-00
Epub
2008-00-01
Pages
258-67
Language
English
Region
England
NLM ID
101226507
PMCID
PMC2822988
Subset
IM
Grants
NHLBI NIH HHS · R21 HL088072 · United States
NHLBI NIH HHS · R21 HL088072-02 · United States
NHLBI NIH HHS · HL088072 · United States
Corrections
CommentIn
PMID: 18813333
CommentIn
PMID: 19039334
External Links
PubMed source DOI: 10.1038/ncpcardio1182 PMC Full Text
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