The clinical and genetic landscape of developmental and epileptic encephalopathies in Egyptian children.

Autor: Elkhateeb N; Department of Clinical Genetics, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.; Department of Pediatrics, Pediatric Neurology and Metabolic Medicine Unit, Kasr Al-Ainy School of Medicine, Cairo University, Cairo, Egypt., Issa MY; Department of Clinical Genetics, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt., Elbendary HM; Department of Clinical Genetics, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt., Elnaggar W; Department of Pediatrics, Pediatric Neurology and Metabolic Medicine Unit, Kasr Al-Ainy School of Medicine, Cairo University, Cairo, Egypt., Ramadan A; Department of Pediatrics, Pediatric Neurology and Metabolic Medicine Unit, Kasr Al-Ainy School of Medicine, Cairo University, Cairo, Egypt., Rafat K; Department of Clinical Genetics, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt., Kamel M; Department of Pediatrics, Pediatric Neurology and Metabolic Medicine Unit, Kasr Al-Ainy School of Medicine, Cairo University, Cairo, Egypt., Abdel-Ghafar SF; Department of Medical Molecular Genetics, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt., Amer F; Department of Pediatrics, Pediatric Neurology and Metabolic Medicine Unit, Kasr Al-Ainy School of Medicine, Cairo University, Cairo, Egypt., Hassaan HM; Department of Pediatrics, Clinical Genetics Unit, Kasr Al-Ainy School of Medicine, Cairo University, Cairo, Egypt., Trunzo R; CENTOGENE GmbH, Rostock, Germany., Pereira C; CENTOGENE GmbH, Rostock, Germany., Abdel-Hamid MS; Department of Medical Molecular Genetics, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt., D'Arco F; Radiology Department, Great Ormond Street Hospital for Children, London, UK., Bauer P; CENTOGENE GmbH, Rostock, Germany., Bertoli-Avella AM; CENTOGENE GmbH, Rostock, Germany., Girgis M; Department of Pediatrics, Pediatric Neurology and Metabolic Medicine Unit, Kasr Al-Ainy School of Medicine, Cairo University, Cairo, Egypt., Gleeson JG; Department of Neurosciences, University of California, San Diego, La Jolla, USA.; Rady Children's Hospital, Rady Children's Institute for Genomic Medicine, San Diego, La Jolla, USA., Zaki MS; Department of Clinical Genetics, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt., Selim L; Department of Pediatrics, Pediatric Neurology and Metabolic Medicine Unit, Kasr Al-Ainy School of Medicine, Cairo University, Cairo, Egypt.
Jazyk: angličtina
Zdroj: Clinical genetics [Clin Genet] 2024 May; Vol. 105 (5), pp. 510-522. Date of Electronic Publication: 2024 Jan 14.
DOI: 10.1111/cge.14481
Abstrakt: Developmental and epileptic encephalopathies (DEEs) are a heterogeneous group of epilepsies characterized by early-onset, refractory seizures associated with developmental regression or impairment, with a heterogeneous genetic landscape including genes implicated in various pathways and mechanisms. We retrospectively studied the clinical and genetic data of patients with genetic DEE who presented at two tertiary centers in Egypt over a 10-year period. Exome sequencing was used for genetic testing. We report 74 patients from 63 unrelated Egyptian families, with a high rate of consanguinity (58%). The most common seizure type was generalized tonic-clonic (58%) and multiple seizure types were common (55%). The most common epilepsy syndrome was early infantile DEE (50%). All patients showed variable degrees of developmental impairment. Microcephaly, hypotonia, ophthalmological involvement and neuroimaging abnormalities were common. Eighteen novel variants were identified and the phenotypes of five DEE genes were expanded with novel phenotype-genotype associations. Obtaining a genetic diagnosis had implications on epilepsy management in 17 patients with variants in 12 genes. In this study, we expand the phenotype and genotype spectrum of DEE in a large single ethnic cohort of patients. Reaching a genetic diagnosis guided precision management of epilepsy in a significant proportion of patients.
(© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
Externí odkaz: