Therapeutic implications of etiology-specific diagnosis of early-onset developmental and epileptic encephalopathies (eo-dees): a nationwide Turkish cohort study

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dc.contributor.authorKanmaz, Seda
dc.contributor.authorTekgül, Hasan
dc.contributor.authorAydın, Kürşad
dc.contributor.authorKılıç, Betül
dc.contributor.authorTopçu, Yasemin
dc.contributor.authorÖzpınar, Esra
dc.contributor.authorCansu, Ali
dc.date.accessioned2025-10-15T09:41:53Z
dc.date.available2025-10-15T09:41:53Z
dc.date.issued2024
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, Çocuk Sağlığı ve Hastalıkları Ana Bilim Dalı
dc.description.abstractObjective: To evaluate the etiology-specific diagnosis of early-onset developmental epileptic encephalopathies (EO-DEEs) in a nationwide Turkish cohort to determine the implications for therapeutic management. Methods: The cohort comprised 1450 patients who underwent EO-DEE. The utility of genetic testing was assessed with respect to the initial phases of next generation sequencing (NGS) (2005–2013) and the current NGS era (2014–2022). A predefined four-stepwise diagnostic model was evaluated using cost-effectiveness analysis. The diagnostic and potential therapeutic yields of the genetic tests were subsequently determined. Results: Gene-related EO-DEEs were identified in 48.3 % (n = 701) of the cohort: non-structural genetic (62.6 %), metabolic genetic (15.1 %), and structural genetic (14.1 %). The most common nonstructural genetic variants were SCN1A (n = 132, 18.8 %), CDKL5 (n = 30, 4.2 %), STXBP1 (n = 21, 2.9 %), KCNQ2 (n = 21, 2.9 %), and PCDH19 (n = 17, 2.4 %). The rate of ultra-rare variants (< 0.5 %) was higher in the NGS era (52 %) than that in the initial phase (36 %). The potential therapeutic yields with precision therapy and antiseizure drug modification were defined in 34.5 % and 56.2 % in genetic-EO-DEEs, respectively. The diagnostic model provided an etiology-specific diagnosis at a rate of 78.7 %: structural (nongenetic) (31.4 %), genetic (38.5 %), metabolic (6.1 %), and immune-infectious (2.8 %). Based on a cost-effectiveness analysis, the presented diagnostic model indicated the early implementation of whole-exome sequencing for EO-DEEs. Significance: In the present cohort, the higher rate (48.3 %) of gene-related EO-DEE diagnoses in the NGS era provides a potential therapeutic management plan for more patients.
dc.identifier.citationKanmaz, S., Tekgül, H., Aydın, K., Kılıç, B., Topçu, Y., Özpınar, E. ... Cansu, A. (2024). Therapeutic implications of etiology-specific diagnosis of early-onset developmental and epileptic encephalopathies (eo-dees): a nationwide Turkish cohort study. Seizure, 123, 17-25. http://dx.doi.org/10.1016/j.seizure.2024.09.021
dc.identifier.doi10.1016/j.seizure.2024.09.021
dc.identifier.endpage25
dc.identifier.issn1059-1311
dc.identifier.issn1532-2688
dc.identifier.pmid39447234
dc.identifier.scopus2-s2.0-85207266740
dc.identifier.scopusqualityQ2
dc.identifier.startpage17
dc.identifier.urihttp://dx.doi.org/10.1016/j.seizure.2024.09.021
dc.identifier.urihttps://hdl.handle.net/20.500.12511/13108
dc.identifier.volume123
dc.identifier.wosWOS:001344253400001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorAydın, Kürşad
dc.institutionauthorKılıç, Betül
dc.institutionauthorTopçu, Yasemin
dc.institutionauthorÖzpınar, Esra
dc.institutionauthorid0000-0003-1513-6149
dc.institutionauthorid0000-0003-0884-2635
dc.language.isoen
dc.relation.ispartofSeizure
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/embargoedAccess
dc.subjectEarly-Onset Developmental Epileptic Encephalopathies
dc.subjectGenetic Testing
dc.subjectPrecision Medicine
dc.subjectStepwise Diagnostic Model
dc.titleTherapeutic implications of etiology-specific diagnosis of early-onset developmental and epileptic encephalopathies (eo-dees): a nationwide Turkish cohort study
dc.typeArticle

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