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Genetics of dilated cardiomyopathy

Ray E Hershberger, MD
Section Editors
William J McKenna, MD
Benjamin A Raby, MD, MPH
Deputy Editor
Susan B Yeon, MD, JD, FACC


Dilated cardiomyopathy (DCM) is a common cause of heart failure (HF) and is the most common diagnosis in patients referred for cardiac transplantation. DCM is characterized by dilatation and systolic dysfunction of one or both ventricles. (See "Definition and classification of the cardiomyopathies".)

DCM is classified as idiopathic (idiopathic dilated cardiomyopathy, or IDC) when all usual clinically detectable, except genetic, causes have been excluded. Such detectable causes of DCM include ischemic DCM and a variety of toxic, metabolic, or infectious agents (see "Causes of dilated cardiomyopathy"). Although specialists commonly apply the diagnosis of IDC to DCMs of unknown cause, an etiology is present but undetected.

Family-based studies of first-degree relatives during the 1990s established that familial dilated cardiomyopathy (familial DCM) can be identified in 20 to 35 percent of patients diagnosed with IDC by clinical screening (electrocardiography, echocardiography) of family members. Most familial DCM is transmitted in an autosomal dominant inheritance pattern, although all inheritance patterns have been identified (autosomal recessive, X-linked, and mitochondrial). During the past 20 years, familial DCM genetic studies have identified mutations in more than 30 genes.

Most patients with a genetic basis causing their DCM will have an initial diagnosis of IDC. Given the frequency of familial DCM, evaluation of new IDC cases should include a careful three to four generation family history and clinical screening of first-degree family members as described below.

Developments have dramatically and favorably affected efforts to identify and understand the genetic basis of DCM, including the enormous impact of next generation sequencing (NGS) and the availability of very large databases of exome or genome sequences that can be used as reference sequences in gene discovery programs (eg, the Exome Study Project, Exome Variant Server, the Thousand Genomes Project, the Exome Aggregation Consortium [ExAC], and the Genome Aggregation Database [gnomAD]). Extensive discovery studies over the past 20 years have identified rare variants in numerous genes.

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Literature review current through: Nov 2017. | This topic last updated: Nov 07, 2017.
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