Utility of genetic testing in children with developmental and epileptic encephalopathy (DEE) at a tertiary hospital in South Africa: A prospective study
| dc.contributor.advisor | Van Toorn, Ronald | en_ZA |
| dc.contributor.advisor | Moosa, Shahida | en_ZA |
| dc.contributor.advisor | Solomons, Regan | en_ZA |
| dc.contributor.author | Essajee, Farida | en_ZA |
| dc.date.accessioned | 2021-11-25T09:08:25Z | en_ZA |
| dc.date.accessioned | 2022-02-22T10:21:37Z | en_ZA |
| dc.date.available | 2021-11-25T09:08:25Z | en_ZA |
| dc.date.issued | 2021-12 | en_ZA |
| dc.description | Thesis (MMed) -- Stellenbosch University, 2021. | en_ZA |
| dc.description.abstract | ENGLISH ABSTRACT: Introduction: The developmental and epileptic encephalopathies (DEE) are a heterogeneous group of rare neurodevelopmental disorders, characterised by early-onset seizures that are often intractable, electroencephalographic abnormalities, and developmental delay or regression. Studies have shown that 70% of epilepsy cases have a genetic basis. Next-generation sequencing (NGS) technologies have led to the identification of several epilepsy-related genes, including those responsible for DEE. The reported diagnostic yield of an NGS-based testing for patients with epilepsy ranges from 10 to 40%, depending on the test and the phenotypes among the studied cohorts. Objectives: The aim of this study was to evaluate the diagnostic yield of NGS-based epilepsy gene panel in children with DEE and to assess the value of the genetic results to the parents and managing physicians. Design: A prospective cohort study of 41 consecutive children diagnosed with DEE (onset before 3 years of age) was recruited over a 2-year period (2019-2021). Pre- and post-test genetic counselling were offered to all study participants. The results were classified into three categories: positive (pathogenic/likely pathogenic), inconclusive (variant of unknown significance), or negative. After the results were obtained, questionnaires were administered to both the physicians and the parents. Result interpretation and careful matching of the variant to the clinical phenotype was carried out with the help of a medical geneticist. Results: We found a positive genetic diagnosis in 20 of 41 (48%) children. Variants in SCN1A (n=5), KANSL1 (n=2), KCNQ2 (n=2) and CDKL5 (n=2) accounted for the greatest number of positive findings. Rarer genetic findings included IQSEC2, KCNMA1, SMC1A and STXBP. All except 1 of the pathogenic variants identified fully explained and matched the respective phenotypic description in the patient at time of diagnosis. Gene-specific treatment changes were initiated in 26% patients following the genetic diagnosis. Both parents and physicians expressed usefulness of genetic testing in patients with DEE. Conclusion: With this study, we show that an NGS gene panel is highly effective in diagnosing South African children with DDE. The study diagnostic yield (48%) is similar to previously reported paediatric cohorts, and the genetic findings proved useful for therapeutic decision making and genetic counseling. Although the diagnostic yield in this study was high, therapeutic consequences and ultimate improvement of the patient's clinical state were still limited. | en_ZA |
| dc.description.abstract | "Geen opsomming beskikbaar." | en_ZA |
| dc.description.version | Masters | en_ZA |
| dc.embargo.terms | 2022-05-31 | en_ZA |
| dc.format.extent | 52 pages | en_ZA |
| dc.identifier.uri | http://hdl.handle.net/10019.1/124264 | en_ZA |
| dc.language.iso | en_ZA | en_ZA |
| dc.publisher | Stellenbosch : Stellenbosch University | en_ZA |
| dc.rights.holder | Stellenbosch University | en_ZA |
| dc.subject | Human chromosome abnormalities -- Diagnosis | en_ZA |
| dc.subject | High-throughput nucleotide sequencing | en_ZA |
| dc.subject | Neonatal encephalopathy | en_ZA |
| dc.subject | Genetic disorders -- Diagnosis -- Sub-Saharan Africa | en_ZA |
| dc.subject | Epilepsy – Hospitals -- Sub-Saharan Africa | en_ZA |
| dc.subject | Epileptic children -- Sub-Saharan Africa | en_ZA |
| dc.title | Utility of genetic testing in children with developmental and epileptic encephalopathy (DEE) at a tertiary hospital in South Africa: A prospective study | en_ZA |
| dc.type | Thesis | en_ZA |