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

Molecular autopsy — post-mortem search for pathogenic variants in inherited arrhythmia syndromes and cardiomyopathies

This systematic review with meta-analysis estimates the yield of postmortem genetic testing after sudden cardiac death between ages 1 and 50. Sixty-six studies, covering 4,452 cases from 23 countries, were included after searching Ovid MEDLINE and Ovid Embase, with risk of bias assessed using the Joanna Briggs Institute checklist. The pooled detection rate of pathogenic variants was 19% (95% CI 15–24%), and 76% of detected variants involved genes on the ACMG Secondary Findings list. Higher detection rates were associated with earlier publication years, lower mean age and lower risk of bias, with major and persistent between-study heterogeneity (I² = 91%) despite subgroup and meta-regression analyses.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

One case in five explained is enough to support systematic molecular autopsy after sudden death in the young, provided DNA sampling and storage have been organised beforehand. Heterogeneity at 91% means this 19% should be read as an order of magnitude and not as a figure to quote to a family: actual yield depends on autopsy phenotype, age and panel used. The proportion of variants in ACMG genes is a reminder that the main benefit goes to living relatives, through cascade screening.

Analysis by Dr Thibaut Benquey