CARDIOVASCULAR JOURNAL OF AFRICA • Volume 33, No 5, September/October 2022 AFRICA 285 without any cardiac changes. Research suggest that this might be explained by the progressive nature of cardiomyopathy, whereby in the first stages of the disease the myocardial changes may be so incipient that it may not be visible at autopsy.1,8,20,24 The genetic basis of DCM in infants commonly demonstrates phenotypic overlap. Reported cases of DCM due to SCN5A variations identified in long-QT syndrome type 3 (LQT3), shows that not only can it result from structural changes in the myocytes, but also from altered calcium ion handling.10,15,16,19-21 These inherited genetic susceptibilities in infant cases have been proven to play an important role in how the cardiac muscle responds to environmental and infectious factors.11,22,24 Researchers believe that variations in the SCN5A gene, with its associated higher risk of lethal arrhythmias, are linked to an increase in an infant’s critical vulnerability to certain infections. Consequently, acute viral infections are regarded as one of the provocative factors associated with sudden death in infant channelopathy and/or DCM cases.11,20,23,24 In fact, many of these SUID cases (diagnosed with inherited cardiac arrhythmogenic disorders) demonstrated a viral prodrome within days of their death. Such infants often present with respiratory signs, extreme sleepiness, difficulty in feeding and increased fussiness prior to death.11,23,24 It is not uncommon for inherited channelopathies and/ or cardiomyopathies 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.1,8,11,20 Consequently, it is even of greater importance for countries with a high burden of infectious diseases to be especially aware of these findings, as there might be a reasonable tendency to overcall minor findings of viral infection in these SUID cases.1,2,11,20 Genetic testing is considered an ideal risk-assessment tool, not only for channelopathies, but for cardiomyopathies as well, due to its ability to identify patients at risk prior to overt disease development.1,10,22-24 The use of post mortem genetic testing in SUID cases can benefit family members, especially those from poor communities, by providing the first indication of a familial cardiac arrhythmogenic disorder. Ultimately this will allow for the opportunity of preventative intervention, which can be used to avoid the progressive onset of the disease.8,10,15, 22,23 For decades now, the undeniable benefit of post mortem genetic testing in SUID cases, especially those that remain unexplained, has been widely recognised worldwide.1,4,8 The continued advancement in molecular diagnostics and its associated decrease in costs has allowed for expanded molecular testing using cardiac gene panels and next-generation sequencing.1,4,9,24 Although this is not a novel concept to most first-world countries, it still eludes the radar of many medical professionals practicing in an economically and resourcestrained country. These countries, including South Africa, have not yet been conducting post mortem genetic testing in unexplained SUID cases, at least not routinely.2,3,7,12 The greatest benefit of such testing is not to define the cause of death, but rather the highly disease-specific diagnostic, therapeutic and prognostic benefit derived from subsequent genetic screening of family members of the deceased.1,8,15,16 In addition, disease-causing variants in the SCN5A gene have been reported as a possible predisposing factor of SUID, providing an apparent aetiology of arrhythmias due to secondary challenges/risk factors such as complicating lower respiratory infections, which are generally tolerated in infants not carrying such genetic variations. Considering South Africa’s burden of infectious diseases coupled with a high infant survival rate in most of these cases, a more scrutinised and in-depth investigation into those SUID cases that typically present with no more than minimal findings such as the presence of a mild infection, should be considered.2,12 Conclusion There is a lack of research reporting on the genetics of channelopathies and cardiomyopathies in Africa. The fact that cardiomyopathies are deemed an endemic form of non-communicable diseases, of high importance in the largely low-income communities inSSA, proves theneed for local research on this topic. The results from this case study demonstrate the possible impact molecular diagnostics can have on identifying potential inherited cardiac disorders. Additionally, it highlights the occurrence of misdiagnosis of SUID cases in our population, or the possibility of an incomplete understanding pertaining to the circumstances surrounding these deaths. Further molecular testing may provide better knowledge as to why certain infants do not survive these viral and/or bacterial infections. This case study aimed to create awareness on this subject among medical professionals, especially those practicing in resource-strained countries. Hopefully, this will motivate for more collaborative research and investigation to gain a better understanding of the unique genetic diversity and its associated inherited diseases in SSA. The authors thank the Genomic Research Institute from the University of Pretoria, South Africa, for funding the research. Ethics approval for this study was obtained from the Faculty of Health Sciences Research Ethics Committee, University of Pretoria (UP) (142/2014). References 1. 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: 54–63. 2. Dempers JJ, Burger EH, du Toit-Prinsloo L, et al. A South African perspective. In: Duncan JR, Byard RW, eds. SIDS – Sudden Infant and Early Childhood Death: The Past, the Present and the Future. Adelaide: The University of Adelaide Press, 2018: 375–389. 3. Heathfield LJ, Martin LJ, Ramesar R. Massively parallel sequencing in sudden unexpected death in infants: A case report in South Africa. Forensic Sci Int Genet Suppl Ser 2019; 7: 459–461. 4. Duncan JR, Byard RW. Sudden infant death syndrome: An overview. In: Duncan JR, Byard RW, eds. SIDS – Sudden Infant and Early Childhood Death: The Past, the Present and the Future. Adelaide: The University of Adelaide Press, 2018: 15–33. 5. Dempers JJ, Coldrey J, Burger EH. The institution of a standardized investigation protocol for sudden infant death in the eastern metropole, Cape Town, South Africa. J Forens Sci 2016; 61(6): 1508–1514. 6. Filiano JJ, Kinney HC. A perspective on neuropathologic findings in victims of the sudden infant death syndrome: The triple-risk model. Biol Neonate 1994; 65: 194–197. 7. Byard RW. Sudden infant death syndrome: Definitions. In: Duncan JR, Byard RW, eds. SIDS – Sudden Infant and Early Childhood Death: The
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