Case report: Additional variants induced sudden cardiac death among pediatric ACM with DSG2 homozygous mutant genotype: a report of three cases

In conclusion, we report three rare cases of ACM with the same homozygous <i>DSG2</i> variant in combination with additional heterozygous mutations in cardiomyopathy-associated genes. A systematic review of all the ACM cases with homozygous <i>DSG2</i> variants demonstrated that the additional genetic variants contributed to the aggravated clinical manifestations and worse clinical symptoms of the ACM patients because of homozygous <i>DSG2</i> mutations, including early disease onset and lethal cardiac events. Our data suggested that comprehensive genetic evaluation should be performed to identify any potential additional pathogenic variants that may significantly influence the clinical prognosis and outcomes of patients with ACM. The knowledge of underlying molecular mutations would be useful in designing better therapeutic strategies for ACM patients with multiple genetic mutations.