{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T15:01:34Z","timestamp":1747148494412,"version":"3.40.5"},"reference-count":43,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T00:00:00Z","timestamp":1714348800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Mutations in the cyclin\u2010dependent kinase\u2010like 5 gene (CDKL5) are associated with a wide spectrum of clinical presentations. Early\u2010onset epileptic encephalopathy (EOEE) is the most recognized phenotype. Here we describe phenotypic features in eight Tunisian patients with CDKL5\u2010related encephalopathy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We included all cases with clinical features consistent with CDKL5\u2010related encephalopathy: infantile epileptic spasm, acquired microcephaly, movement disorders and visual impairment. We collected data about seizure types, electroencephalogram, magnetic resonance imaging, and metabolic analysis. The diagnosis of CDKL5 mutation was made thanks to Sanger sequencing with an ABI PRISM 3100\u2010Avant automated DNA sequencer using a Big Dye Terminator Cycle Sequencing Reaction Kit v1.1. and Next Generation Sequencing (NGS) since the development of a gene panel responsible for DEE within the framework of \u201cStrengthening the Sfax University Expertise for diagnosis and management of epileptic encephalopathies\u201d.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We collected four boys and four girls aged meanly 6\u2009years old with confirmed mutation on CDKL5 gene. Overall, we identified five de novo CDKL5 mutations including three Frame\u2010shift mutations, one missense mutation, and a splicing variant. The mean age at first seizure onset was 4\u2009months. The first seizure type was infantile epileptic spasm (4\/8) followed by tonic (2\/8) and myoclonic seizures (2\/8). Out of eight cases, four exhibited two stages epileptic course while epilepsy in three other patients progressed on three stages. Regarding development, most cases (6\/8) had psychomotor retardation from the start whilst the two others showed psychomotor regression with the onset of seizures. Additional clinical features included visual impairment (7\/8), tone abnormalities (7\/8), stereotypies (7\/8), and acquired microcephaly (6\/8).<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Our present report delineates an unusual phenotype of CDKL5\u2010related encephalopathy with male gender predominance and delayed onset epilepsy. It interestingly described new phenotypic features and uncommon benign developmental profiles in boys, different patterns of CDKL5\u2010epilepsy, neuroimaging findings, and CDKL5 mutational spectrum.<\/jats:p><\/jats:sec>","DOI":"10.1002\/epi4.12824","type":"journal-article","created":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T08:11:39Z","timestamp":1694592699000},"page":"906-917","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["First report of Tunisian patients with <i>CDKL5<\/i>\u2010related encephalopathy"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2918-3819","authenticated-orcid":false,"given":"Chahnez","family":"Charfi\u00a0Triki","sequence":"first","affiliation":[{"name":"Child Neurology Department, Hedi Chaker Sfax University Hospital, and Research Laboratory LR19ES15 University of Sfax  Sfax Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2298-3613","authenticated-orcid":false,"given":"Salma","family":"Zouari\u00a0Mallouli","sequence":"additional","affiliation":[{"name":"Child Neurology Department, Hedi Chaker Sfax University Hospital, and Research Laboratory LR19ES15 University of Sfax  Sfax Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marwa","family":"Ben\u00a0Jdila","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Functional Genetics, Faculty of Science of Sfax University of Sfax  Sfax Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4098-4537","authenticated-orcid":false,"given":"Mariem","family":"Ben\u00a0Said","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Screening Processes (LPCMC), Center of Biotechnology of Sfax University of Sfax  Sfax Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5058-7693","authenticated-orcid":false,"given":"Fatma","family":"Kamoun\u00a0Feki","sequence":"additional","affiliation":[{"name":"Child Neurology Department, Hedi Chaker Sfax University Hospital, and Research Laboratory LR19ES15 University of Sfax  Sfax Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Weckhuysen","sequence":"additional","affiliation":[{"name":"Applied &amp; Translational Neurogenomics Group, VIB Center for Molecular Neurology, VIB University of Antwerp  Antwerp Belgium"},{"name":"Department of Neurology Antwerp University Hospital  Antwerp Belgium"},{"name":"Translational Neurosciences, Faculty of Medicine and Health Science University of Antwerp  Antwerp Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabeur","family":"Masmoudi","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Screening Processes (LPCMC), Center of Biotechnology of Sfax University of Sfax  Sfax Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faiza","family":"Fakhfakh","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Functional Genetics, Faculty of Science of Sfax University of Sfax  Sfax Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,4,29]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2018100848"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1159\/000331333"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn197"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2012.12.030"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2019.02.015"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32606"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17239"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13670"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13709"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky471"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_12_13_1","unstructured":"gnomAD.Genome Aggregation. 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