Abstract

Background. Dilated cardiomyopathy (DCM) is an important cause of heart failure in children and may have a genetic basis, particularly in cases with early disease onset and a positive family history. Genetic heterogeneity may contribute to differences in clinical presentation and disease severity. Objective. To describe the clinical, laboratory, echocardiographic, radiological, and genetic characteristics of three pediatric cases with familial and genetically determined dilated cardiomyopathy. Case Series. Three children aged 6–13 years with severe dilated cardiomyopathy were retrospectively evaluated. Clinical assessment, electrocardiography, echocardiography, laboratory investigations, chest radiography, and next-generation sequencing-based genetic analysis were performed. All patients demonstrated progressive heart failure, reduced exercise tolerance, growth retardation, and marked left ventricular systolic dysfunction. Echocardiography showed severe left ventricular dilatation and reduced ejection fraction ranging from 22% to 23%. NT-proBNP levels were elevated in all cases, reaching 6930 pg/mL in one patient. A heterozygous splice-site variant in the FLNC gene, c.4737+1G>T, was identified in all three patients and was classified as likely pathogenic. Additional rare variants of uncertain significance were detected in TNNI3K, MYBPC3, MAP2K1, and RBCK1, which may potentially contribute to phenotypic variability. Conclusion. These pediatric cases demonstrate severe early-onset DCM associated with a likely pathogenic Filamin C (FLNC) splice-site variant and additional rare genetic variants. The findings support the value of comprehensive genetic evaluation and family-based assessment in children with early-onset DCM and suggest that genetic heterogeneity may contribute to differences in clinical severity.