The clinical utility of pediatric cardiomyopathy genetic testing: From diagnosis to a precision medicine-based approach to care.

Abstract

Pediatric-onset cardiomyopathies are rare yet cause significant morbidity and mortality in affected children. Genetic testing has a major role in the clinical evaluation of pediatric-onset cardiomyopathies, and identification of a variant in an associated gene can be used to confirm the clinical diagnosis and exclude syndromic causes that may warrant different treatment strategies. Further, risk-predictive testing of first-degree relatives can assess who is at-risk of disease and requires continued clinical follow-up. In this review, we seek to describe the current role of genetic testing in the clinical diagnosis and management of patients and families with the five major cardiomyopathies. Further, we highlight the ongoing development of precision-based approaches to diagnosis, prognosis, and treatment. Emerging application of genotype-phenotype correlations opens the door for genetics to guide a precision medicine-based approach to prognosis and potentially for therapies. Despite advances in our understanding of the genetic etiology of cardiomyopathy and increased accessibility of clinical genetic testing, not all pediatric cardiomyopathy patients have a clear genetic explanation for their disease. Expanded genomic studies are needed to understand the cause of disease in these patients, improve variant classification and genotype-driven prognostic predictions, and ultimately develop truly disease preventing treatment.