CARDIOVASCULAR JOURNAL OF AFRICA • Volume 33, No 5, September/October 2022 282 AFRICA The added value of molecular-based diagnostics in the African forensic medical setting Barbara Ströh van Deventer, Musa Aubrey Makhoba, Lorraine du Toit-Prinsloo, Chantal van Niekerk Abstract Sudden unexpected infant death (SUDI) is reported to be an extraordinarily high burden in sub-Saharan Africa, with the incidence rate in South Africa among the highest in the world. It is common for the cause of many such infant deaths to remain unexplained even after a full medico-legal death investigation, and then to be categorised as a sudden unexplained infant death (SUID). Fortunately, advances in molecular-based diagnostics allow researchers to identify numerous underlying inherited cardiac arrhythmogenic disorders in many SUDI cases, with a predominance of variants identified in the SCN5A gene. Such cardiac arrhythmogenic-related sudden deaths generally present with no structural alterations of the heart that are macroscopically identifiable at autopsy, therefore highlighting the importance of post mortem genetic testing. We report on a significant genetic finding that was made on a SUDI case in which the cause was ascribed to an acute bacterial pneumonia but it was still subjected to post mortem genetic testing of the SCN5A gene. The literature shows that many SUDI cases diagnosed with inherited cardiac arrhythmogenic disorders have demonstrated a viral prodrome within days of their death. It is therefore not uncommon for these cardiac disorders in infants to be mistaken for flu, viral upper respiratory tract infection or pneumonia, and without the incorporation of post mortem genetic testing, any other contributory causes of these deaths are often disregarded. This study highlights the need for research reporting on the genetics of inherited cardiac disorders in Africa. Keywords: channelopathies, dilated cardiomyopathy (DCM), inherited cardiac disorders, post mortem genetic testing, SCN5A, sudden unexpected death in an infant (SUDI). Submitted 25/5/21; accepted 2/9/22 Cardiovasc J Afr 2022; 33: 282–286 www.cvja.co.za DOI: 10.5830/CVJA-2022-050 Sudden deaths in infants are still considered one of the leading causes of infant mortality worldwide and have also been reported to be an extraordinarily high burden in sub-Saharan Africa (SSA).1-3 According to Duncan et al.,4 for most countries, the rate of sudden unexplained infant deaths (SUIDs) [or the previously termed sudden infant death syndrome (SIDS) cases] is reported at approximately 0.2–0.5 per 1 000 live births. The most recent published incidence rate for South African SUID cases was 1.06 per 1 000 live births for the white population and 3.41 for infants from the mixed-ancestry population group, respectively.2 The investigation into SUDIs and child mortality remains a high-priority research area in South Africa.2-3,5 It has universally been accepted that a SUID case can very rarely be explained by a convenient and simplistic ‘single-cause’ mechanism, but instead is attributed to a complex event with an increase in incidence when risk factors such as vulnerability, a critical period in development and exogenous stressors all intersect at the same time (triple-risk model proposed by Filiano and Kinney).4,6,7 One of these risk factors, and a possible preventable cause of SUIDs, which has received increased attention over the past few years is inheritable cardiac arrhythmogenic disorders.1,3,4 Although these inherited cardiac disorders in SUID cases have primarily been associated with electrical conditions (channelopathies), recent studies have identified variants in genes encoding structural proteins, thereby suggesting a cardiomyopathy as a possible cause of death as well.1,8-10 Previous studies demonstrated a link between SUIDs and a predominance of SCN5A gene variants. This could be explained by the known genotype–phenotype correlations that suggest patients with SCN5A variants may experience a higher mortality rate, mostly occurring during sleep, compared to patients suffering from variants in other genes involved in inherited cardiac diseases.1,8 Advances in molecular-based diagnostics allow researchers to identify numerous underlying inherited cardiac arrhythmogenic disorders that have been misdiagnosed in many SUID cases.1,11 In many developing countries, including Africa, there is still a significant lack as far as forensic molecular diagnostics is concerned, mainly due to financial and resource constraints.12 As a result, the cases in this study were subjected to retrospective post mortem molecular analysis of only the most prevalent gene (SCN5A) associated with SUID, in order to identify any possible pathogenic variations associated with an inherited cardiac disease, which may have predisposed this infant to a sudden death. Case report We report on a case of a two-month-old male infant of African ancestry whose mother found him unresponsive in his crib during a scheduled nap. Upon emergency medical services (EMS) arrival, the infant was declared dead at the scene without Department of Forensic Medicine, University of Pretoria, Pretoria, South Africa Barbara Ströh van Deventer, MSc, barbara.vandeventer@yahoo.com Musa Aubrey Makhoba, MB ChB (Pret), FC For Path (SA), Dip For Med (SA) (Path) Lorraine du Toit-Prinsloo, MB ChB (Pret), Dip For Med (SA) Path, MMed (Path) (Forens), FC For Path (SA), FRC Path (Aus) Department of Forensic Medicine, Sydney, Australia Lorraine du Toit-Prinsloo, MB ChB (Pret), Dip For Med (SA) Path, MMed (Path) (Forens), FC For Path (SA), FRC Path (Aus) Department of Chemical Pathology, University of Pretoria, and Department of Chemical Pathology, National Health Laboratory Services, Pretoria, South Africa Chantal van Niekerk, PhD
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