Genetic testing identified pathogenic variants in 66% of hypertrophic cardiomyopathy cases and 80% in restrictive cardiomyopathy, aiding precise clinical diagnoses.
Does genetic testing identify pathogenic variants and inform clinical diagnosis in children with cardiomyopathy?
Genetic testing in childhood cardiomyopathy provides a high diagnostic yield, particularly in restrictive and hypertrophic phenotypes, which can refine clinical diagnosis and inform prognosis.
Absolute Event Rate: 0% vs 0%
Background: The causes of cardiomyopathy in children are less well described than in adults. We evaluated the clinical diagnoses and genetic causes of childhood cardiomyopathy and outcomes of cascade genetic testing in family members. Methods: We recruited children from a pediatric cardiology service or genetic heart diseases clinic. We performed Sanger, gene panel, exome or genome sequencing and classified variants for pathogenicity using American College of Molecular Genetics and Genomics guidelines. Results: Cardiomyopathy was diagnosed in 221 unrelated children aged ≤18 years. Children mostly had hypertrophic cardiomyopathy (n=98, 44%) or dilated cardiomyopathy (n=89, 40%). The highest genetic testing diagnostic yields were in restrictive cardiomyopathy (n=16, 80%) and hypertrophic cardiomyopathy (n=65, 66%), and lowest in dilated cardiomyopathy (n=26, 29%) and left ventricular noncompaction (n=3, 25%). Pathogenic variants were primarily found in genes encoding sarcomere proteins, with TNNT2 and TNNI3 variants associated with more severe clinical outcomes. Ten children (4.5%) had multiple pathogenic variants. Genetic test results prompted review of clinical diagnosis in 14 families with syndromic, mitochondrial or metabolic gene variants. Cascade genetic testing in 127 families confirmed 24 de novo variants, recessive inheritance in 8 families, and supported reclassification of 12 variants. Conclusions: Genetic testing of children with cardiomyopathy supports a precise clinical diagnosis, which may inform prognosis.
Bagnall et al. (Thu,) reported a other. Genetic testing identified pathogenic variants in 66% of hypertrophic cardiomyopathy cases and 80% in restrictive cardiomyopathy, aiding precise clinical diagnoses.