Postmortem genetic testing identified pathogenic or likely pathogenic variants in 33.3% of selected sudden unexpected death cases with inconclusive conventional autopsies.
Cohort (n=12)
No
Does postmortem genetic testing improve the diagnostic yield in cases of unexplained sudden death?
Combining pathological autopsy with postmortem genetic testing improves diagnostic yield in unexplained sudden death, uncovers hidden hereditary cardiac conditions, and enables targeted surveillance for relatives.
Abstract Background Anatomopathological autopsy and postmortem genetic testing play a crucial role in forensic medicine, particularly in elucidating the causes of sudden death (SD) that remain unexplained by conventional methods. This study explores their value in detecting inherited cardiac conditions with medico-legal and preventive implications. Methods From a 15-year forensic cohort, 12 cases of sudden unexpected death in which conventional autopsy was inconclusive or where a hereditary cardiac condition was suspected, were analyzed. Each case underwent histology, toxicology, and targeted next-generation sequencing panels covering genes associated with channelopathies and cardiomyopathies. Variants were classified according to ACMG/AMP guidelines, and family studies were performed when feasible. Results Integrated pathological and genetic analysis identified pathogenic or likely pathogenic variants in several cases, notably in RYR2 and CALM2 (channelopathies) and FLNC and PPP1R13L (cardiomyopathies). In these cases, genetic findings confirmed the diagnosis, while variants of uncertain significance were detected in others. Postmortem genetic testing proved essential in cases with structurally normal hearts or sub-diagnostic findings, such as concealed arrhythmogenic cardiomyopathy. Familial cascade testing uncovered additional carriers, enabling targeted surveillance and preventive measures. Conclusion Combining pathological autopsy and postmortem genetic testing significantly improves the diagnostic yield in unexplained SD, uncovers hidden hereditary cardiac conditions, and provides critical information for risk assessment in relatives. Beyond clinical implications, these findings contribute to accurate forensic determinations and prevention of miscarriages of justice. Integrating genetic studies into forensic protocols should become standard practice to ensure both scientific rigor and legal fairness. Clinical trial registration Not applicable.
Sabater-Molina et al. (Fri,) conducted a cohort in Sudden unexpected death (SUD) (n=12). Postmortem genetic testing (targeted NGS panels) was evaluated on Identification of pathogenic or likely pathogenic variants. Postmortem genetic testing identified pathogenic or likely pathogenic variants in 33.3% of selected sudden unexpected death cases with inconclusive conventional autopsies.