Next generation sequencing (NGS)-based tests have become routine first-line investigative modalities in paediatric neurology clinics in many high-income countries (HICs). Studies from these countries show that these tests are both cost-effective and reliable in diagnosing many complex childhood neurological diseases. However, NGS-based testing in low-and middle-income countries (LMICs) is limited. The primary objective of this study was to evaluate the diagnostic yield and impact of targeted gene panel sequencing in a selected paediatric cohort attending a tertiary paediatric neurology clinic in the Western Cape Province of South Africa. This retrospective study included 124 consecutive paediatric patients with neurological disease, aged 6 weeks to 17years, referred for NGS-based multi-gene panel testing over a 41-month period. Twenty-four different disease group-specific panels were utilized. A caregiver experience questionnaire was administered when a pathogenic variant was identified. The overall study diagnostic yield (DY) was 45% (56/124 patients). It was highest for neuromuscular disorders 52% (13/25), cerebral palsy spectrum disorders 31% (5/16) and early-onset epilepsies 41% (26/63). Testing proved inconclusive (variants of uncertain significance) in 38% (47/124). The majority of caregivers (97%) viewed NGS-based testing as a positive experience The diagnostic yield in this study is similar to previously reported paediatric cohorts in HICs. The high yields for neuromuscular disorders and early epileptic encephalopathies suggest that NGS-based panels may be more cost-effective as first-line testing in well-defined phenotypes. The latter finding argues for early inclusion of all children with developmental epileptic encephalopathies (DEE), as early diagnosis leads to better treatment and avoidance of unnecessary investigations.

Magriet van Niekerk
Tygerberg Hospital, Stellenbosch University
South Africa

Ronald van Toorn
Tygerberg Hospital, Stellenbosch University
South Africa

Regan Solomons
Tygerberg Hospital, Stellenbosch University
South Africa

Shahida Moosa
Tygerberg Hospital, Stellenbosch University
South Africa