Evaluation of genetic, clinical features, and prognosis in pediatric patients diagnosed with cardiomyopathy.

BACKGROUND: Pediatric cardiomyopathy (PCM) comprises a genetically heterogeneous, high risk group of myocardial disorders and is a leading cause of pediatric heart failure and transplantation. Genotype-phenotype correlations and outcome data remain limited, particularly in populations with high consanguinity. METHODS: We conducted a retrospective cohort study of 53 children with cardiomyopathy classified as hypertrophic (HCM), dilated (DCM), left ventricular noncompaction (LVNC), or restrictive cardiomyopathy (RCM). We analyzed demographics, consanguinity, echocardiographic parameters, genetic testing results (available in 26/53 patients, 49.1%), device therapy, transplantation, and mortality. RESULTS: The cohort included 20 HCM (37.7%), 17 DCM (32.1%), 13 LVNC (24.5%), and 3 RCM (5.7%) patients, with a median age at diagnosis of 6.5 years (interquartile range [IQR] 2.0-10.0). Consanguinity was documented in 24 of 53 patients (45.3%). A pathogenic or likely pathogenic (P/LP) variant was identified in 9 of 26 tested patients (34.6%), corresponding to 17.0% of the total cohort (9/53). When variants of uncertain significance (VUS) are included, 20 of 26 tested patients (76.9%) harbored at least one rare variant; however, 11 of these 20 findings (42.3% of tested patients) were VUS, which are not counted toward diagnostic yield and remain subject to reclassification. Baseline ejection fraction was markedly reduced in DCM (median 35%, IQR 28-37%), whereas HCM and RCM had preserved systolic function at diagnosis. During a median follow up of 3.0 years, 15 patients (28.3%) underwent implantable cardioverter defibrillator implantation, 6 (11.3%) underwent heart transplantation, and 18 (34.0%) died; mortality was highest in DCM (58.8%) and RCM (66.7%). CONCLUSION: Among the 26 of 53 patients who underwent genetic testing, PCM in this cohort showed a P/LP diagnostic yield of 34.6% (9/26) and substantial mortality, particularly in DCM and RCM phenotypes. High consanguinity was associated with a notable P/LP yield and a frequent VUS burden; whether consanguinity contributes to earlier or more severe disease requires confirmation in larger, prospective studies. These findings support offering comprehensive genetic testing to pediatric cardiomyopathy patients, especially in high consanguinity settings, to enable molecular diagnosis and structured family counseling. In this cohort, a substantial proportion of tested patients had P/LP variants, and many others carried VUS that will require ongoing re evaluation. Future prospective studies should assess how specific genetic findings, combined with imaging and functional parameters, can be incorporated into validated risk stratification and management algorithms. s.