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

Autor:	Esterhuizen AI; The South African MRC/UCT Genomic and Precision Medicine Research Unit, Division of Human Genetics, Institute of Infectious Diseases and Molecular Medicine, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; National Health Laboratory Service, Groote Schuur Hospital, Cape Town, South Africa., Tiffin N; South African National Bioinformatics Institute, University of the Western Cape, Bellville, Western Cape, South Africa., Riordan G; Department of Paediatric Neurology, Red Cross War Memorial Children's Hospital, Neuroscience Institute, University of Cape Town, Cape Town, South Africa., Wessels M; Department of Paediatric Neurology, Red Cross War Memorial Children's Hospital, Neuroscience Institute, University of Cape Town, Cape Town, South Africa., Burman RJ; Division of Clinical Neurology, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom., Aziz MC; Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Northwestern University, Chicago, IL., Calhoun JD; Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Northwestern University, Chicago, IL., Gunti J; Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Northwestern University, Chicago, IL., Amiri EE; Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Northwestern University, Chicago, IL., Ramamurthy A; Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Northwestern University, Chicago, IL., Bamshad MJ; Department of Pediatrics, University of Washington, Seattle, WA; Department of Genome Sciences, University of Washington, Seattle, WA; Brotman Baty Institute, Seattle, WA., Mefford HC; Centre for Pediatric Neurological Disease Research, St. Jude Children's Research Hospital, Memphis, TN., Ramesar R; The South African MRC/UCT Genomic and Precision Medicine Research Unit, Division of Human Genetics, Institute of Infectious Diseases and Molecular Medicine, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; National Health Laboratory Service, Groote Schuur Hospital, Cape Town, South Africa., Wilmshurst JM; Department of Paediatric Neurology, Red Cross War Memorial Children's Hospital, Neuroscience Institute, University of Cape Town, Cape Town, South Africa. Electronic address: jo.wilmshurst@uct.ac.za., Carvill GL; Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Northwestern University, Chicago, IL; Department of Pharmacology, Northwestern University Feinberg School of Medicine, Northwestern University, Chicago, IL; Department of Pediatrics, Northwestern University Feinberg School of Medicine, Northwestern University, Chicago, IL. Electronic address: gemma.carvill@northwestern.edu.
Jazyk:	angličtina
Zdroj:	Genetics in medicine : official journal of the American College of Medical Genetics [Genet Med] 2023 Feb; Vol. 25 (2), pp. 100333. Date of Electronic Publication: 2022 Dec 08.
DOI:	10.1016/j.gim.2022.11.002
Abstrakt:	Purpose: Sub-Saharan Africa bears the highest burden of epilepsy worldwide. A presumed proportion is genetic, but this etiology is buried under the burden of infections and perinatal insults in a setting of limited awareness and few options for testing. Children with developmental and epileptic encephalopathies (DEEs) are most severely affected by this diagnostic gap in Africa, because the rate of actionable findings is highest in DEE-associated genes. Methods: We tested 234 genetically naive South African children diagnosed with/possible DEE using gene panels, exome sequencing, and chromosomal microarray. Statistical comparison of electroclinical features in children with and children without candidate variants was performed to identify characteristics most likely predictive of a positive genetic finding. Results: Of the 41 (of 234) children with likely/pathogenic variants, 26 had variants supporting precision therapy. Multivariate regression modeling highlighted neonatal or infantile-onset seizures and movement abnormalities as predictive of a positive genetic finding. We used this, coupled with an emphasis on precision medicine outcomes, to propose the pragmatic "Think-Genetics" strategy for early recognition of a possible genetic etiology. Conclusion: Our findings emphasize the importance of an early genetic diagnosis in DEE. We designed the Think-Genetics strategy for early recognition, appropriate interim management, and genetic testing for DEE in resource-constrained settings. Competing Interests: Conflict of Interest The authors declare no conflicts of interest. (Copyright © 2022 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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