Unusual Genetic Variant in Familial Dilated Cardiomyopathy Identified Through Pediatric Case Investigation

Introduction

Dilated cardiomyopathy (DCM) is a rare but serious cause of heart failure in children. In idiopathic cases, especially when familial, a genetic etiology is often implicated.

Method

We report the case of a 2-year-old boy admitted for generalized edema and signs of heart failure. Echocardiography revealed DCM with markedly reduced left ventricular ejection fraction. His paternal aunt had been previously diagnosed with DCM in adulthood. A full etiological assessment, including whole exome sequencing (WES), was performed.

Results

WES identified a heterozygous pathogenic variant in the TTN gene (OMIM 188840), associated with autosomal dominant isolated familial DCM (OMIM 604145) and familial hypertrophic cardiomyopathy 9 (OMIM 613765). Additionally, a heterozygous likely pathogenic variant was found in the CTNNA3 gene, associated with autosomal dominant arrhythmogenic right ventricular dysplasia type 13 (OMIM 615616). Both variants are rare and scarcely reported in the literature. These findings supported a genetic diagnosis and led to extended family screening and early clinical monitoring.

Conclusion

This case underscores the value of whole exome sequencing in pediatric DCM, enabling the identification of rare genetic variants with major implications for diagnosis, prognosis, and family management.