Detection rate of pathogenic variants by postmortem genetic testing for sudden cardiac death among children and young adults: Systematic review and meta-analysis

Purpose Postmortem genetic testing (PMGT) can clarify the causes of sudden cardiac death (SCD) in children and young adults and provide preventive care for relatives. We systematically reviewed studies to estimate the detection rate of pathogenic variants identified by PMGT in SCD cases aged 1–50 years and examined factors influencing detection rates. Methods Ovid MEDLINE and Ovid Embase were searched for observational studies on PMGT in cases of SCD, records in duplicate were screened, and study- and variant-level data were extracted. Risk of bias was assessed using the Joanna Briggs Institute checklist. The pooled detection rates were estimated using random-effects meta-analysis, and heterogeneity was explored based on subgroup and meta-regression analyses. Results Sixty-six studies (4,452 cases from 23 countries) were included. The pooled detection rate was 19% (95% confidence interval, 15% to 24%). Among the detected pathogenic variants, 76% were found in genes included on the ACMG Secondary Findings list. Higher detection rates were associated with earlier publication years, lower mean age, and lower risk of bias. Substantial between-study heterogeneity persisted ( I 2 = 91%) despite the subgroup and meta-regression analyses. Conclusion PMGT can be used to identify pathogenic variants in young SCD cases, however, there is considerable heterogeneity in study conditions.