From Genetic Diagnosis to Clinical Management: The Critical Role of Whole Genome Sequencing in Inherited Cardiomyopathies

Hereditary cardiomyopathies are mostly autosomal dominant disorders that affect cardiac muscle structure and function, often leading to arrhythmias, heart failure, or sudden cardiac death. We report two brothers (aged 41 and 38), who presented with inherited cardiomyopathy and a family history of suspected cardiac disease in their father. The older sibling was referred for genetic evaluation due to clinical symptoms suggestive of cardiomyopathy. Whole genome sequencing (WGS), followed by targeted analysis of cardiomyopathy-associated genes, identifi ed a pathogenic heterozygous variant in the FLNC gene (c.7384+1G>T) located at the canonical donor splice site. The fi nding was consistent with the patient’s phenotype. In conjunction with the current clinical guidelines, an implantable cardioverter-defi brillator (ICD) was implanted as primary prevention of sudden cardiac death (SCD). Cascade genetic screening identifi ed the same FLNC variant in his younger, asymptomatic brother. He was enrolled in a structured surveillance program with personalized lifestyle recommendations. This case illustrates the critical role of WGS in establishing a defi nitive molecular diagnosis, informing clinical decision-making, and enabling timely intervention and clinical management. It also underscores the importance of family-based screening in inherited cardiomyopathies, even when the family history is limited or unconfi rmed. Integration of genomic tools into cardiology practice can enhance early detection, improve outcomes, and facilitate precision medicine strategies in affected families.