Precision medicine for developmental and epileptic encephalopathies in Africa—strategies for a resource-limited setting

Esterhuizen, Alina; Tiffin, Nicki; Riordan, Gillian; Wessels, Margreet; Burman, Richard J; Aziz, Miriam C.; Gunti, Jonathan; Amiri, Ezra E.; Ramamurthy, Aishwarya; Mefford, Heather C; Ramesar, Raj; Wilmshurst, Jo M; Carvill, Gemma L.; Bamshad, Michael J.; Leal, Suzanne M.; Nickerson, Deborah A.; Anderson, Peter; Bacus, Tamara J.; Blue, Elizabeth; Brower, Katherine; Buckingham, Kati J.; Chong, Jessica X.; Sánchez, Diana Cornejo; Davis, Colleen; Davis, Chayna; Frazar, Christian D.; Gomeztagle-Burgess, Katherine; Gordon, William W.; Horike‐Pyne, Martha; Hurless, Jameson R.; Jarvik, Gail P.; Johanson, Eric; Kolar, J. Thomas; Marvin, Colby T.; McGee, Sean; McGoldrick, Daniel; Mekonnen, Betselote; Nielsen, Patrick M.; Patterson, Karynne; Radhakrishnan, Aparna; Richardson, M; Roote, Gwendolin T.; Ryke, Erica; Schrauwen, Isabelle; Shively, Kathryn M.; Smith, Joshua D.; Tackett, Monica; Wang, Gao; Weiss, Jeffrey M.; Wheeler, Marsha M.; Yi, Qing; Zhang, Xiaohong

doi:10.1016/j.gim.2022.11.002

Cited by 8 publications

(5 citation statements)

References 41 publications

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“…SCN1A, CDKLA5 and KCNQ2 were also among the top ve genes with the highest yield using NGS in studies focusing on paediatric epilepsy in a study by Mei et al (6). A recent study from the South Africa using a panel of 71 DEE-associated genes identi ed Pathogenic/Likely pathogenic candidate single nucleotide variant or short indels in 12% of cases (28/234 patients) (7). Similar to our study, SCN1A proved the most prevalent gene in this category (n = 13).…”

Section: Discussionsupporting

confidence: 87%

Utility of Next Generation Sequencing in Paediatric Neurological Disorders: experience from South Africa

Moosa

Niekerk

Toorn

et al. 2023

Preprint

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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 cost. The primary objective of this study was to evaluate the diagnostic yield and impact of targeted gene panels 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, referred for 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 53% (66/124 patients). It was highest for neuromuscular disorders 64% (16/25), cerebral palsy spectrum disorders 54% (9/16) and early-onset epilepsies 44% (28/63). 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.

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Section: Discussionsupporting

confidence: 87%

Utility of Next Generation Sequencing in Paediatric Neurological Disorders: experience from South Africa

Moosa

Niekerk

Toorn

et al. 2023

Preprint

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“…Among these studies, six were case reports, 6–11 each featuring a small sample size or individual cases. In contrast, larger‐scale studies inlcuding three cohorts, 12–14 five were trials 5,15–18 and two were retrospective studies 19,20 . One study was prospective study with a smaller sample size, emphasizing a diagnostic approach involving brain MRI 4 .…”

Section: Resultsmentioning

confidence: 99%

“…This prospective study, along with the use of WES, significantly contributes to our understanding of the role of genetics in the management of epilepsy. However, several studies 7,13,14,16,18,20,21 did not provide specific details regarding the genes under investigation, diagnostic methods, treatments, or outcomes. Consequently, the significance of these studies remains unclear due to the limited information provided.…”

Section: Discussionmentioning

confidence: 99%

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Precision medicine approaches in epilepsy: A systematic review of genetic markers and personalized treatment strategies

Agarwal,

Kaur,

Ashfaque

et al. 2024

Precision Medical Sciences

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Epilepsy is one of the most common neurological diseases globally. We conducted a systematic review of the genetic markers and personalized treatment strategies used in the precision medicine treatment of epilepsy. An exhaustive electronic search was carried out on PubMed and Google Scholar, spanning from inception up to June 2023 on epilepsy and biomarkers. A total of 45 articles from PubMed and 19 articles from Google Scholar were imported and screened based on studies that focused primarily on genetic markers and precision methods for epilepsy subtyping, treatment strategies, outcomes, and adverse effects. Reviews and studies not in English were excluded. Full‐text data extraction, coding, and analysis were carried out with Microsoft Excel. For the risk of bias assessment of the final included studies, the Critical Appraisal Skills Program checklist was used. A total of 19 studies were analyzed in the review. The SLC35A2 gene saw a reduction in seizure frequency with d‐galactose treatment while the KCNQ2 gene saw improvement with phenytoin, carbamazepine, and retigabine. GRIN2D gene saw varying improvements with memantine. KCNT1 gene saw improvement with only a combination of quinidine and topiramate, quinidine was not useful when used alone. Other studies involved the identification of different markers using gene and exome sequencing. These studies collectively provide a diverse range of insights into epilepsy, with variations in study design, sample size, age groups, and diagnostic criteria, highlighting the multifaceted nature of epilepsy research. These studies contribute to our understanding of epilepsy diagnosis and management in different clinical settings, however, there were some limitations such as QT prolongation was observed with specific medications and participant heterogeneity. Small sample sizes reduced statistical power and brief durations of studies limited their ability for long‐term analysis. Although most studies had a low risk of bias, two studies demonstrated some reporting bias. Fianlly, the absence of biomarkers is a limitation that impedes the study's capacity to explore underlying biological mechanisms.

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“…Analisis FTIR pada konsentrasi filler 0,75% w/v Perbandingan dengan studi lain, seperti yang dilakukan oleh Thandavamoorthy (2013), menunjukkan keberadaan puncak yang serupa untuk C-O stretching, O-H bending, dan gugus alkohol dalam serat selulosa pisang, yang menunjukkan pola umum interaksi kimia dalam bahan berbasis alami [7]. Analisis yang dilakukan oleh Gunti (2023) pada ekstrak kulit Sweetinia mahagoni juga menunjukkan keberadaan ikatan O-H dan N-H yang serupa, yang menandakan gugus hidroksil bebas dan ikatan amina primer, yang berperan dalam reduksi dan stabilisasi nanopartikel perak [14]. Dalam konteks bioadhesif, keberadaan gugus-gugus ini sangat penting karena mereka mempengaruhi interaksi antar molekul dan dengan substrat yang diikat, yang pada gilirannya mempengaruhi efektivitas adhesi.…”

Section: Analisis Hasil Uji Ftirunclassified

Analisis Pengaruh Penambahan Magnesium Oksida terhadap Sifat Mekanis Bioadhesif Berbasis Kitosan-Karagenan

Amanda,

Budhijanto,

Ramadhani

2024

J. Teknik Kimia

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This study investigates the effect of magnesium oxide (MgO) as a filler in enhancing the bioadhesive properties of chitosan and carrageenan-based adhesives. The primary focus is on improving tensile strength, viscosity, solid content, and thermal properties. The results indicate that the addition of 0.75% w/v MgO significantly increased tensile strength from 9.76 kPa to 21.76 kPa and viscosity from 34.26 cP to 617 cP with a 0.5% w/v MgO addition. The solid content also increased from 9.81% to 13.19% with increased MgO concentration. The addition of benzoyl peroxide (BPO) reduced curing time, enhancing process efficiency. Scanning Electron Microscopy and Fourier Transform Infrared Spectroscopy confirmed improvements in structural and chemical stability, while Differential Scanning Calorimetry showed better curing efficiency. This study suggests MgO as a potential filler to improve mechanical properties and adhesion of bioadhesives, relevant for medical applications.

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Precision medicine for developmental and epileptic encephalopathies in Africa—strategies for a resource-limited setting

Cited by 8 publications

References 41 publications

Utility of Next Generation Sequencing in Paediatric Neurological Disorders: experience from South Africa

Utility of Next Generation Sequencing in Paediatric Neurological Disorders: experience from South Africa

Precision medicine approaches in epilepsy: A systematic review of genetic markers and personalized treatment strategies

Analisis Pengaruh Penambahan Magnesium Oksida terhadap Sifat Mekanis Bioadhesif Berbasis Kitosan-Karagenan

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