Postmortem genetic testing in young individuals: What clinical medical practitioners need to know
DOI:
https://doi.org/10.7196/SAMJ.2022.v112i12.16800Keywords:
Postmoterm, GeneticsAbstract
The death of a young person is most often a tragic occurrence, more so when this death was unexpected. Forensic pathologists are mandated to investigate such deaths, and there has been a strong move internationally towards genetic testing as an additional investigative tool. The aim of our article is to bring the advantage of implementing the so-called molecular autopsy in a local setting to the attention of medical practitioners. When a multidisciplinary approach is taken in cases of sudden unexpected death, the benefits to family members, and society as a whole, are irrefutable.
References
Van den Heuvel LM, Do J, Yeates L, et al. Global approaches to cardiogenetic evaluation after sudden cardiac death in the young: A survey among healthcare professionals. Heart Rhythm 2021;18(10):1637- 1644. https://doi.org/10.1016/j.hrthm.2021.03.037
Tani N, Ikeda T, Oritani S, et al. Application of molecular pathology in forensic medical diagnosis. In: Ishikawa T (ed). Forensic Medicine and Human Cell Research – New Perspective and Bioethics. Singapore: Springer; 2019:29-43. https://doi.org/10.1007/978-981-13-2297-6_3
Gunn P, Walsh S, Roux C. The nucleic acid revolution continues – will forensic biology become forensic molecular biology? Front Genet 2014;5(44):1-4. https://doi.org/10.3389/fgene.2014.00044
Cunningham KS. The promise of molecular autopsy in forensic pathology practice. Acad Forensic
Pathol 2017;7(4):551-556. https://doi.org/10.23907/2017.047
Emergen Research. Molecular forensics market by product (Instruments, Software), by technology
(polymerase chain reaction (PCR), capillary electrophoresis, NGS, by application (radioactive toxicology, nucleic acid analysis), by end user, and by region, Forecasts to 2027. Globe Newswire, 2020. https://www.globenewswire.com/news-release/2020/12/16/2145826/0/en/Molecular-Forensics- Market-Size-Worth-USD-2-223-7-Million-by-2027-Growing-at-a-CAGR-of-9-8-Emergen-Research. html (accessed 21 March 2021).
Wong CX, Brown A, Lau DH, et al. Epidemiology of sudden cardiac death: Global and regional perspectives. Heart Lung Circ 2019;28(1):6-14. https://doi.org/10.1016/j.hlc.2018.08.026
Fellmann F, van El CG, Charron P, et al. European recommendations integrating genetic testing into multidisciplinary management of sudden cardiac death. Eur J Hum Genet 2019;27(12):1763-1773. https://doi.org/10.1038/s41431-019-0445-y
Stiles MK, Wilde AAM, Abrams DJ, et al. 2020 APHRS/HRS Expert consensus statement on the investigation of decedents with sudden unexplained death and patients with sudden cardiac arrest, and of their families. J Arrhythm 2021;18(1):1-54. https://doi.org/10.1002/joa3.12449
Ribeiro S, Coelho L, Puentes K, et al. Postmortem genetic testing: Clinical diagnosis is not ended by the patient’s death. Rev Port Cardiol 2019;38(7):503-509. https://doi.org/10.1016/j.repce.2019.09.001
Priori SG. Genetic testing to predict sudden cardiac death: Current perspectives and future goals. Indian Heart J 2013;66(Suppl 1):S58-S60. https://doi.org/10.1016/j.ihj.2013.11.004
Gulino SP, Burns K, Gunther WM, et al. Improving forensic pathologic investigation of sudden death in the young: Tools, guidance, and methods of cardiovascular dissection from the sudden death in the young case registry. Acad Forensic Pathol 2018;8(2):347-391. https://doi. org/10.1177/1925362118782077
Basso C, Aguilera B, Banner J, et al. Guidelines for autopsy investigation of sudden cardiac death: 2017 update from the Association for European Cardiovascular Pathology. Virchows Arch 2017;471(6):691- 705. https://doi.org/10.1007/s00428-017-2221-0
Ntusi N. Cardiovascular disease and global health: A perspective from the global South. SA Heart 2020;17(2):134-139. https://doi.org/ https://doi.org/10.24170/17-2-4154
Jankelow D, Manga P, Ntsekhe M, et al. SA Heart statement on COVID-19 and cardiovascular disease. SA Heart 2020;17(3):258-262. https://doi.org/10.24170/17-3-4390
Byrne J, Eksteen G, Crickmore C. Cardiovascular disease statistics reference document. Heart and Stroke Foundation South Africa, 2016. https://www.heartfoundation.co.za/wp-content/ uploads/2017/10/CVD-Stats-Reference-Document-2016-FOR-MEDIA-1.pdf (accessed 11 February 2021).
Lemos MP, Taylor TE, McGoldrick S, et al. Pathology-based research in Africa. Clin Lab Med 2018;38(1):67-90. https://doi.org/10.1016/j.cll.2017.10.006
Yuyun MF, Sliwa K, Kengne AP, et al. Cardiovascular diseases in sub-Saharan Africa compared to high-income countries: An epidemiological perspective. Global Heart 2020;15(1):1-18. https://doi. org/10.5334/gh.403
Herath JC, Liu O. Sudden natural deaths in Ontario, Canada: A retrospective autopsy analysis (2012 - 2016). J Forensic Sci Med 2020;6(1):8-26. https://doi.org/10.4103/jfsm.jfsm_50_19
Lucena JS. Sudden cardiac death. Forensic Sci Res 2019;4(3):199-201. https://doi.or/10.1080/209617 90.2019.1622062
Andersen JD, Jacobsen SB, Trudsø LC, et al. Whole genome and transcriptome sequencing of post- mortem cardiac tissues from sudden cardiac death victims identifies a gene regulatory variant in NEXN. Int J Legal Med 2019;133(6):1699-1709. https://doi.org/10.1007/s00414-019-02127-9
Tiemensma M, Burger EH. Sudden and unexpected deaths in an adult population, Cape Town, South Africa, 2001 - 2005. S Afr Med J 2012;102(2):90-94.
Scheiper S, Ramos-Luis E, Blanco-Verea A, et al. Sudden unexpected death in the young – value of massive parallel sequencing in postmortem genetic analyses. Forensic Sci Int 2018;293(1):70-76. https://doi.org/10.1016/j.forsciint.2018.09.034
Giudicessi JR, Ackerman MJ. Role of genetic heart disease in sentinel sudden cardiac arrest survivors across the age spectrum. Int J Cardiol 2017;270(1):214-220. https://doi.org/10.1016/j. ijcard.2018.05.100
Hellenthal N, Gaertner-Rommel A, Klauke B, et al. Molecular autopsy of sudden unexplained deaths reveals genetic predispositions for cardiac diseases among young forensic cases. Europace 2017;19(11):1881-1890. https://doi.org/10.1093/europace/euw247
Johannsen EB, Baughn LB, Sharma N, et al. The genetics of sudden infant death syndrome ‒ towards a gene reference resource. Genes 2021;12(2):216. https://doi.org/10.3390/ genes12020216
Köffer J, Scheiper-Welling S, Verhoff MA, et al. Post-mortem genetic investigation of cardiac disease- associated genes in sudden infant death syndrome (SIDS) cases. Int J Legal Med 2021;135(1):207-212. https://doi.org/10.1007/s00414-020-02394-x
Mak CM, Mok NS, Shum HC, et al. Sudden arrhythmia death syndrome in young victims: A five-year retrospective review and two-year prospective molecular autopsy study by next generation sequencing and clinical evaluation of their first-degree relatives. Hong Kong Med J 2019;25(1):21-29. https://doi. org/10.12809/hkmj187256
Cann F, Corbett M, O’Sullivan D, et al. Phenotype-driven molecular autopsy for sudden cardiac death. Clin Genet 2017;91(1):22-29. https://doi.org/10.1111/cge.12778
Heart and Stroke Foundation South Africa. Sudden cardiac deaths in athletes. HSFSA, 2015. www. heartfoundation.co.za/media-releases/sudden-cardiac-deaths-athletes (accessed 28 January 2022).
Ackerman M, Atkins DL, Triedman JK, et al. Sudden cardiac death in the young. Circulation 2016;133(10):1006-1026. https://doi.org/10.1161/CIRCULATIONAHA.115.020254
Markwerth P, Bajanowski T, Tzimas I, et al. Sudden cardiac death ‒ update. Int J Legal Med 2021;135(2):483- 495. https://doi.org/10.1007/s00414-020-02481-z
Van Driel B, Michels M, van der Velden J. Molecular autopsy. Neth Heart J 2018;26(10)1-2. https://doi. org/10.1007/s12471-018-1157-6
Rizzo S, Carturan E, De Gaspari M, et al. Update on cardiomyopathies and sudden cardiac death. Forensic Sci Res 2019;4(3):202-210. https://doi.org/10.1080/20961790.2019.1631957
Agboola KM, McGill T, Boilson BA, et al. The role of genetic testing in the evaluation of dilated cardiomyopathies. Case Rep Cardiol 2021;1(1):1-4. https://doi.org/10.1155/2021/6641108
Brodeh A, Ebbinghaus H, Deutsch M, et al. Human induced pluripotent stem-cell-derived cardiomyocytes as models for genetic cardiomyopathies. Int J Mol Sci 2019;20(18):4381. https://doi.org/10.3390/ ijms20184381
Skinner JR, Winbo A, Abrams D, et al. Channelopathies that lead to sudden cardiac death: Clinical and genetic aspects. Heart Lung Circ 2019;28(1):22-30. https://doi.org/10.1016/j.hlc.2018.09.007
McNally EM, O’Donnell CJ. Genetic contribution to common heart failure ‒ not so rare? JAMA Cardiol 2021;6(4):387. https://doi.org/10.1001/jamacardio.2020.6508
Sanchez O, Campuzano O, Fernandez Falgueras A, et al. Natural and undetermined sudden death: Value of postmortem genetic investigation. PLoS ONE 2016;11(12):e0167358. https://doi.org/10.1371/journal. pone.0167358
De Beer C, Ayele BT, Dempers J. Immune biomarkers as an adjunct diagnostic modality of infection in cases of sudden and unexpected death in infancy (SUDI) at Tygerberg Medico-legal Mortuary, Cape Town, South Africa. Hum Pathol Case Rep 2021;23(1):1-5. https://doi.org/10.1016/j.ehpc.2021.200477
Fernández-FalguerasA,Sarquella-BrugadaG,BrugadaJ,etal.Cardiacchannelopathiesandsuddendeath: Recent clinical and genetic advances. Biology 2017;6(1):1-21. https://doi.org/10.3390/biology6010007
Marey I, Fressart V, Rambaud C, et al. Clinical impact of post-mortem genetic testing in cardiac death and cardiomyopathy. Open Med 2020;15(1):435-446. https://doi.org/10.1515/med-2020-0150
Campuzano O, Beltramo P, Fernandez A, et al. Molecular autopsy in a cohort of infants died suddenly at rest. Forensic Sci Int Genet 2018;37(1):54-63. https://doi.org/10.1016/j.fsigen.2018.07.023
Vos A, van der Wal AC, Teeuw AH, et al. Cardiovascular causes of sudden unexpected death in children and adolescents (0 - 17 years): A nationwide autopsy study in the Netherlands. Neth Heart J 2018;26(10):500-505. https://doi.org/10.1007/s12471-018-1152-y
Giudicessi JR, Ackerman MJ. Genotype- and phenotype-guided management of congenital long QT syndrome. Curr Probl Cardiol 2013;38(10):417-455. https://doi.org/10.1016/j.cpcardiol.2013.08.001
Micheu MM, Popescu I, Căpățînă CO, et al. Molecular autopsy in sudden cardiac death – ethical issues and clinical implication for relatives. Rom J Leg Med 2016;24(3):157-163. https://doi.org/10.4323/ rjlm.2016.157
McGuire AL, Moore Q, Majumder M, et al. The ethics of conducting molecular autopsies in cases of sudden death in the young. Genome Res 2016;26(9):1165-1169. https://doi.org/10.1101/ gr.192401.115
Moore QL, Majumder MA, Rutherford LK, et al. Ethical and legal challenges associated with public molecular autopsies. J Law Med Ethics 2016;44(2):309-318. https://doi. org/10.1177/1073110516654124
Heathfield LJ, Martin LJ, Ramesar R. A systematic review of molecular autopsy studies in sudden infant death cases. J Pediatr Genet 2018;7(4):143-149. https://doi.org/10.1055/s-0038-1668079
Van Deventer BS, du Toit-Prinsloo L, van Niekerk C. Feasibility of analysis of the SCN5A gene in paraffin embedded samples in sudden infant death cases at the Pretoria Medico-Legal Laboratory, South Africa. Forensic Sci Med Pathol 2018;14(3):276-284. https://doi.org/10.1007/s12024-018-9995-5
Downloads
Published
Issue
Section
License
Copyright (c) 2022 B Stroh van Deventer, L du Toit-Prinsloo, C van Niekerk
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Licensing Information
The SAMJ is published under an Attribution-Non Commercial International Creative Commons Attribution (CC-BY-NC 4.0) License. Under this license, authors agree to make articles available to users, without permission or fees, for any lawful, non-commercial purpose. Users may read, copy, or re-use published content as long as the author and original place of publication are properly cited.
Exceptions to this license model is allowed for UKRI and research funded by organisations requiring that research be published open-access without embargo, under a CC-BY licence. As per the journals archiving policy, authors are permitted to self-archive the author-accepted manuscript (AAM) in a repository.
Publishing Rights
Authors grant the Publisher the exclusive right to publish, display, reproduce and/or distribute the Work in print and electronic format and in any medium known or hereafter developed, including for commercial use. The Author also agrees that the Publisher may retain in print or electronic format more than one copy of the Work for the purpose of preservation, security and back-up.