Key result
Structured postmortem genetic testing identifies pathogenic variants in ~13% of young sudden unexplained death cases.
Why the study?
Sudden unexplained death in young adults may result from hereditary cardiovascular disorders undetected by conventional autopsy, necessitating routine postmortem genetic testing.
Does a structured postmortem investigation integrating genetic counselling and testing improve the identification of hereditary cardiovascular disorders in sudden unexplained death among young adults?
Cohort (n=100)
Yes
Does a structured postmortem investigation integrating genetic counselling and testing improve the identification of hereditary cardiovascular disorders in sudden unexplained death among young adults?
A structured multidisciplinary postmortem procedure integrating genetic testing and pretest counselling identified a definitive pathogenic variant in 13% of young adult sudden unexplained deaths, facilitating targeted preventative screening for surviving blood relatives.
Supports structured postmortem genetic testing in young sudden unexplained death; leaves open optimal family screening strategies pending larger prospective studies.
Introduction Sudden unexplained death (SUD) in young adults may result from hereditary cardiovascular disorders that remain undetected even after conventional autopsy. Routine postmortem genetic testing may identify these disorders, improving determination of the cause of death while providing diagnostic and preventive opportunities for surviving blood relatives. Methods Between September 2022 and October 2025, 100 cases of SUD in young adults in the Netherlands were investigated using the NODOV (Nader Onderzoek naar de DoodsOorzaak bij (jong)Volwassenen) procedure. Genetic counselling was offered to surviving blood relatives in 50 cases where conventional autopsy findings suggested an inherited cardiovascular disorder. Conventional autopsy findings, medical history and family history guided phenotype-directed genetic testing using targeted gene panel analysis following whole-exome/genome sequencing. Results Genetic testing was successfully performed in 46 out of 50 cases and identified pathogenic variants in six cases involving the CACNA1C, BAG3, MYBPC3, LDL-R, KCNJ2, and PKD1 genes. Pretest genetic counselling proved important in guiding genetic testing in 10% of all cases and 50% of genetically confirmed cases. Pathogenic variants were identified in both structurally abnormal and autopsy-negative cases. Families received tailored genetic counselling and recommendations for clinical follow-up based on predictive genetic testing. Among the 44 families without a genetic diagnosis, 43 were advised to undergo clinical cardiovascular screening. Conclusion This study highlights the importance of a structured multidisciplinary postmortem investigation, such as the NODOV procedure, integrating pretest genetic counselling and tailored postmortem genetic testing. This approach may improve determination of cause of death (particularly in autopsy-negative cases), aid in the identification of hereditary cardiovascular disorders and facilitate preventive strategies for at-risk blood relatives.
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Wemeijer et al. (2026) conducted a cohort in Sudden unexplained death (SUD) (n=100). Structured multidisciplinary postmortem investigation (NODOV procedure) was evaluated on Identification of pathogenic or likely pathogenic genetic variants associated with the cause of death. Structured postmortem genetic testing identified pathogenic variants in 13% of successfully tested sudden unexplained death cases among young adults.
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