Next-generation sequencing has made comprehensive genetic testing feasible for inherited cardiomyopathies, shortening diagnostic odysseys despite challenges with inconclusive variant results.
Next-generation sequencing has improved the feasibility of comprehensive genetic testing for inherited cardiomyopathies, though variant interpretation remains a clinical challenge.
Inherited cardiomyopathies include hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, left ventricular noncompaction, and restrictive cardiomyopathy. These diseases have a substantial genetic component and predispose to sudden cardiac death, which provides a high incentive to identify and sequence disease genes in affected individuals to identify pathogenic variants. Clinical genetic testing, which is now widely available, can be a powerful tool for identifying presymptomatic individuals. However, locus and allelic heterogeneity are the rule, as are clinical variability and reduced penetrance of disease in carriers of pathogenic variants. These factors, combined with genetic and phenotypic overlap between different cardiomyopathies, have made clinical genetic testing a lengthy and costly process. Next-generation sequencing technologies have removed many limitations such that comprehensive testing is now feasible, shortening diagnostic odysseys for clinically complex cases. Remaining challenges include the incomplete understanding of the spectrum of benign and pathogenic variants in the cardiomyopathy genes, which is a source of inconclusive results. This review provides an overview of inherited cardiomyopathies with a focus on their genetic etiology and diagnostic testing in the postgenomic era.
Teekakirikul et al. (2012) conducted a review in Inherited cardiomyopathies. Genetic testing was evaluated. Next-generation sequencing has made comprehensive genetic testing feasible for inherited cardiomyopathies, shortening diagnostic odysseys despite challenges with inconclusive variant results.