Clinical Application of Epilepsy Genetics in Africa: Is Now the Time?

Abstract

Over 80% of people with epilepsy live in low- to middle-income countries where epilepsy is often undiagnosed and untreated due to limited resources and poor infrastructure. In Africa, the burden of epilepsy is exacerbated by increased risk factors such as central nervous system infections, perinatal insults, and traumatic brain injury. Despite the high incidence of these etiologies, the cause of epilepsy in over 60% of African children is unknown, suggesting a possible genetic origin. Large-scale genetic and genomic research in Europe and North America has revealed new genes and variants underlying disease in a range of epilepsy phenotypes. The relevance of this knowledge to patient care is especially evident among infants with early-onset epilepsies, where early genetic testing can confirm the diagnosis and direct treatment, potentially improving prognosis and quality of life. In Africa, however, genetic epilepsies are among the most under-investigated neurological disorders, and little knowledge currently exists on the genetics of epilepsy among African patients. The increased diversity on the continent may yield unique, important epilepsy-associated genotypes, currently absent from the North American or European diagnostic testing protocols. In this review, we propose that there is strong justification for developing the capacity to offer genetic testing for children with epilepsy in Africa, informed mostly by the existing counseling and interventional needs. Initial simple protocols involving well-recognized epilepsy genes will not only help patients but will give rise to further clinically relevant research, thus increasing knowledge and capacity.

Voltage Gated Sodium Channel Genes in Epilepsy: Mutations, Functional Studies, and Treatment Dimensions

“…More research collaborations and funding are required to promote GWAS in regions with high epilepsy burden. GWAS of epilepsy in epilepsy endemic regions are expected to discover ethnically related polymorphisms and genetic diversity of epilepsy amongst different populations (167).…”

The Medial Olivocochlear Reflex Is Unlikely to Play a Role in Listening Difficulties in Children

“…The MOCR inhibits outer hair cell (OHC) activity in the cochlea, reducing the OHC gain (Gifford & Guinan, 1987; Liberman & Brown, 1986; Siegel & Kim, 1982; Warr & Guinan, 1979). Among other putative MOCR functions, this gain reduction is thought to aid signal detection in noise (for reviews, see Guinan, 2006; Lopez-Poveda, 2018). The role of the MOCR in signal detection in noise is particularly relevant for children who complain of listening difficulties (LiD).…”

<p>Genetic polymorphisms of CYP3A5, CHRM2, and ZNF498 and their association with epilepsy susceptibility: a pharmacogenetic and case–control study</p>

“…Moreover, there was no association between these SNP genetic haplotypes and drug resistance, contrasted with previous studies that showed an association of these genotypes with response to AEDs. 18,19 CYP3A5 rs15524 was found to be related to the metabolism of the AEDs such as tacrolimus and carbamazepine; 20,36,37 however, there is a lack of data regarding its association with epilepsy. Emich-Widera et al failed to confirm the association of CYP3A5 polymorphism with drug resistance in Caucasian children with epilepsy.…”