Clinical utility of next-generation sequencing in children with cryptogenic cerebral palsy; a cohort study from a tertiary paediatric neurology clinic in the Western Cape Province of South Africa
Date
2023-11
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Stellenbosch : Stellenbosch University
Abstract
ENGLISH ABSTRACT: Introduction: Cerebral palsy (CP) is the most common motor disability in childhood. Both genetic and environmental factors contribute to the aetiology of CP. Recent advances in molecular genetics such as next generation sequencing (NGS) and whole exome sequencing (WES) have revolutionized the understanding of aetiology by more precisely classifying these disorders with a molecular cause. This study aimed to determine the clinical utility of NGS/WES in children with cryptogenic CP. Methods: Data was collected from 218 consecutive children with CP aged 3.6-10.5 years, referred over an 18-month period, to the tertiary paediatric neurology service at Tygerberg Academic Hospital. Results: Cryptogenic CP cases accounted for 24.3% (53/218) of cases. NGS/WES was performed in 66% (35/53). Pathogenic/likely pathogenic variants were identified in 37.2% (13/35) within the following genes: ATP1A3, SCN2A, ATM, FOXG1, UBE3A, KCNA2, ADAR1, QDPR, GCDH, SAMHD1, PLP1 duplication and SLC16A2. Cryptogenic CP cases were more likely to exhibit dyskinetic (odds ratio (OR)= 2.86; P-value=0.01; 95% CI=1.34-6.11) or hypotonic (OR =24.96; P-value=0.01; 95% CI=2.99-208.05) phenotypes, and less likely present with seizures (OR=0.23, P-value=0.01; 95% CI=0.11-0.46). Conclusion: The high rate of detecting causative genetic variants in the study, 37.2%, suggests that NGS/WES should be considered as first-line investigations in children with cryptogenic CP, especially those with dyskinetic or hypotonic subtypes and normal or non-specific MRI findings.
AFRIKAANSE OPSOMMING: Geen opsomming beskikbaar.
AFRIKAANSE OPSOMMING: Geen opsomming beskikbaar.
Description
Thesis (MPhil)--Stellenbosch University, 2023.