Utility of Post-Mortem Genetic Testing in Cases of Sudden Arrhythmic Death Syndrome

Figure 1. SADS: Demographic and Clinical Characterization Sudden arrhythmic death syndrome (SADS) (A) more often affected males and individuals 35 years and younger; (B) 72% of SADS deaths occurred during sleep or rest. (C) Whereas three-quarters exhibited no symptoms before death, 13% had a history of seizures.

Figure 2. ACMG Classification of Variants A significantly higher prevalence of variants of unknown significance (VUS) was found in cardiomyopathy genes compared to primary electrical disease genes, and there was a highly unfavorable ratio of VUS to pathogenic and likely pathogenic variants in the cardiomyopathy genes (28:1) per the American College of Medical Genetics (ACMG) classification of 288 variants in 170 cases. P = pathogenic; LP = likely pathogenic.

Central Illustration. Sudden Arrhythmic Death Syndrome: Genetic Testing and Clinical Screening (A to E) Genetic testing via next-generation sequencing in 302 sudden arrhythmic death syndrome (SADS) cases identified pathogenic and likely pathogenic variants in 13% of cases. Clinical screening of relatives in 82 families found 35 relatives from 21 families with a clinical diagnosis of a primary electrical disease: Brugada syndrome (BrS); catecholaminergic polymorphic ventricular tachycardia (CPVT); and long-QT syndrome (LQTS); there was overlap between molecular and clinical diagnosis in 7 families. Combining molecular autopsy with clinical evaluation increased diagnostic yield in surviving families to 39%. VUS = variant of unknown significance.