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.authorid0000-0002-8738-1242
dc.contributor.authorKanmaz, Seda
dc.contributor.authorTekgul, Hasan
dc.contributor.authorKayilioglu, Hulya
dc.contributor.authorAtas, Yavuz
dc.contributor.authorKart, Pinar Ozkan
dc.contributor.authorYildiz, Nihal
dc.contributor.authorAydin, Kursad
dc.date.accessioned2025-04-15T11:50:55Z
dc.date.available2025-04-15T11:50:55Z
dc.date.issued2024
dc.departmentEge Üniversitesi, Tıp Fakültesi, Dahili Bilimler 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., Tekgul, H., Kayilioglu, H., Atas, Y., Kart, P. O., Yildiz, N., Gumus, H., Aydin, K., Kanmaz, S., Olculu, C. B., Dogan, D. E. T., Per, H., Canpolat, M., Gulec, A., Yildirim, N., Turk, E., Celik, N., Ozturk, S., Kumandas, S., . . . Turkish Epistep Concortium. (2024). Therapeutic implications of etiology-specific diagnosis of early-onset developmental and epileptic encephalopathies (EO-DEEs): A nationwide turkish cohort study. Seizure (London, England), 123, 17-25.
dc.identifier.doi10.1016/j.seizure.2024.09.021
dc.identifier.endpage25
dc.identifier.issn10591311
dc.identifier.issueDec
dc.identifier.pmid39447234
dc.identifier.scopus2-s2.0-85207266740
dc.identifier.scopusqualityQ2
dc.identifier.startpage17
dc.identifier.urihttps://doi.org/10.1016/j.seizure.2024.09.021
dc.identifier.urihttps://hdl.handle.net/11454/117084
dc.identifier.volume123
dc.identifier.wosWOS:001344253400001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorKanmaz, Seda
dc.institutionauthorTekgul, Hasan
dc.institutionauthorid0000-0002-8738-1242
dc.language.isoen
dc.publisherW B Saunders Co Ltd
dc.relation.ispartofSeizure - European Journal of Epilepsy
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
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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