Journal Article

Utility of next generation sequencing in paediatric neurological disorders: experience from South Africa

Moosa, Shahida, van Niekerk, Magriet, van Toorn, Ronald, Solomons, Regan

2024

Overview

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 due to affordability constraints. 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 17 years, 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). The diagnostic yield in this study is similar to previously reported paediatric cohorts in HICs. The high yields for neuromuscular disorders (52%) and early epileptic encephalopathies (41%) 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.

• Publisher: Springer International Publishing,Nature Publishing Group
• Subject: 45 / 45/23 / 692/699 / 692/699/375/178 / Adolescent / Bioinformatics / Biomedical and Life Sciences / Biomedicine / Child / Child, Preschool / Children / Cytogenetics / Epilepsy / Female / Gene Expression / Genetic Testing - methods / Genetic Testing - standards / High-Throughput Nucleotide Sequencing - methods / Human Genetics / Humans / Infant / Male / Nervous System Diseases - diagnosis / Nervous System Diseases - genetics / Neurological diseases / Neuromuscular diseases / Next-generation sequencing / Patients / Pediatrics / Phenotypes / Retrospective Studies / South Africa