Abstract
AIM: To evaluate personalized care or precision medicine initiatives, including mobile health (mHealth) technology and genetic screening, in a South African paediatric epilepsy clinic. METHOD: This exploratory prospective observational pilot study included 39 children aged 4 years or older with drug-resistant epilepsy (ongoing seizures despite at least two antiseizure medications at adequate doses). Participants were recruited from the epilepsy service at the Red Cross War Memorial Children's Hospital in Cape Town, the largest paediatric hospital in sub-Saharan Africa. mHealth technology - a wearable device and mobile application - allowed recording of seizures, medication, sleep, mobility, quality of life, and health visits. Genetic testing included a customized gene panel and pharmacogenomic arrays. RESULTS: Seizure frequency, but not duration, was significantly greater in clinical records before and during the study period (8.0 and 5.5 median seizures per month respectively) compared with mHealth records of 2.0 median seizures per month (n = 28, p < 0.001, r = 0.64, 95% confidence interval [CI] 2.62-14.25, Wilcoxon signed-rank test, and n = 21, p < 0.001, r = 0.76, 95% CI 2.25-15.75, Wilcoxon signed-rank test respectively). Wearable devices detected decreased activity and sleep in patients compared with age-matched typically developing peers (both p < 0.001, Mann-Whitney U test). Structural abnormalities were the most common aetiology. Pathogenic variants occurred in two different probands in SCN1A, one likely pathogenic variant in GRIN2A, and two variants of unknown significance in GABRG2 and GRIN2B. Pharmacogenomic analyses identified variants of interest in CYP2D6, EPHX1, and SCN1A. INTERPRETATION: Precision medicine for drug-resistant epilepsy using mHealth and genetics may show use in a resource-limited setting. This study, the first demonstration of precision medicine in an African paediatric setting, informs the development of diagnostic testing and provides novel insights into the lives and genetics of affected children.