Genetic profile and genotype-phenotype correlations in childhood cardiomyopathy

Genetic cardiomyopathy is a rare disease in childhood.

To analyse clinical and genetic aspects of a paediatric cardiomyopathy population, and to establish genotype-phenotype correlations.

We performed a retrospective study of all patients with idiopathic cardiomyopathy aged<18years in Southeast France. Secondary causes of cardiomyopathy were excluded. All data (clinical, echocardiography, genetic testing) were collected retrospectively. Patients were classified into six groups: hypertrophic cardiomyopathy; dilated cardiomyopathy; restrictive cardiomyopathy; left ventricular non-compaction; arrhythmogenic right ventricular dysplasia; and mixed cardiomyopathy. Patients who did not have a complete genetic test according to current scientific developments had another deoxyribonucleic acid blood sample during the study time. Genetic tests were considered positive if the variant found was classified as pathogenic, likely pathogenic or a variant of uncertain significance.

Eighty-three patients were included between 2005 and 2019. Most patients had hypertrophic cardiomyopathy (39.8%) or dilated cardiomyopathy (27.7%). The median age at diagnosis was 1.28years (interquartile range: 0.27-10.48years). Heart transplantation was performed in 30.1% of patients, and 10.8% died during follow-up. Among 64 patients with a complete genetic analysis, 64.1% had genetic anomalies, mostly in MYH7 (34.2%) and MYBPC3 (12.2%) genes. There were no differences in the whole cohort between genotype-positive and genotype-negative patients. In the hypertrophic cardiomyopathy group, 63.6% had a positive genetic test. Patients with a positive genetic test more often had extracardiac impact (38.1% vs. 8.3%; P=0.009), and more often required an implantable cardiac defibrillator (23.8% vs. 0%; P=0.025) or a heart transplant (19.1% vs. 0%; P=0.047).

In our population, children with cardiomyopathy had a high positive genetic test rate. Hypertrophic cardiomyopathy with a positive genetic test is associated with a worse outcome.