Postmortem genetic testing in young individuals: What clinical medical practitioners need to know

Authors

  • B Stroh van Deventer Department of Forensic Medicine, Faculty of Health Sciences, University of Pretoria, South Africa
  • L du Toit-Prinsloo New South Wales Health Pathology, Forensic and Analytical Science Service, Newcastle, Australia
  • C van Niekerk Department of Chemical Pathology, Faculty of Health Sciences, University of Pretoria and National Health Laboratory Service, Pretoria, South Africa

DOI:

https://doi.org/10.7196/SAMJ.2022.v112i12.16800

Keywords:

Postmoterm, Genetics

Abstract

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

2022-12-01

Issue

Section

CME

How to Cite

1.
Stroh van Deventer B, du Toit-Prinsloo L, van Niekerk C. Postmortem genetic testing in young individuals: What clinical medical practitioners need to know. S Afr Med J [Internet]. 2022 Dec. 1 [cited 2024 Dec. 10];112(12):886-9. Available from: https://samajournals.co.za/index.php/samj/article/view/547

Similar Articles

1-10 of 13

You may also start an advanced similarity search for this article.

Most read articles by the same author(s)