Genetic Testing in Pediatric Cardiomyopathies: Diagnostic Yield, Variants of Uncertain Significance and Implications for Genetic Counseling

Pediatric cardiomyopathies are rare but severe disorders and a leading cause of heart failure and transplantation in children. Genetic testing is now recommended in routine evaluation, yet translating results into clinical and family decisions remains complex. This narrative review summarizes current evidence from test selection to genetic counseling. Diagnostic yield ranges from approximately 30% to 45% and varies with phenotype, age at onset, family history and testing strategy. In infants, syndromic, metabolic and mitochondrial disorders account for many diagnoses that are missed by cardiomyopathy gene panels but detected by exome or genome sequencing, preferably as trio analysis. Variants of uncertain significance are frequent, more common in populations underrepresented in reference databases, and subject to reclassification, which affects about one in five tested children over time. We discuss secondary findings, pre- and post-test counseling, management of relatives when only a variant of uncertain significance is identified, surveillance of genotype-positive, phenotype-negative relatives, psychosocial impact and shared responsibility for recontact after reclassification. Finally, we highlight evidence gaps, including the absence of Romanian and Eastern European pediatric data, and propose directions for research and practice.