Genetic testing in pediatric cardiomyopathies: Implications for diagnosis and management

Pediatric cardiomyopathies, such us dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM), left ventricular noncompaction (LVNC) and arrhythmogenic cardiomyopathy (AC), are a heterogeneous group of primary myocardial diseases, often with a genetic nature, which represent an important cause of cardiovascular morbidity and mortality in children. Genetic etiologies comprise sarcomeric and citoskeletal variants as well as Inborn Errors of Metabolism. Paralleling progress in clinical genetic testing, our understanding of the genetic causes of cardiomyopathies both in adults and in children is rapidly improving. In children presenting features suggestive of cardiomyopathies it is recommended to test for the specific causative genes to confirm clinical diagnosis, clarify prognosis and subsequently provide pre-symptomatic testing of at risk relatives. In family members, genetic testing may provide information for risk stratification and interpretation of dubious phenotypes. Genes causing cardiomyopathies can be different in children and in adults. For this reason, the pediatric population requires dedicated genetic panels. Functional studies, such us patch clamp or other in vitro and in vivo techniques used to verify the function of mutant structural macromolecules should be carried out in the presence of variants of unknown significance. However, they are labour intensive and expensive, and cannot be employed routinely in the diagnostic setting. The present review addresses the distinctive genetic features of pediatric cardiomyopathies and the appropriate interpretation strategies for test results