Therapeutic implications of etiology-specific diagnosis of early-onset developmental and epileptic encephalopathies (EO-DEEs): A nationwide Turkish cohort study
| dc.contributor.author | Kanmaz S. | |
| dc.contributor.author | Tekgul H. | |
| dc.contributor.author | Kayilioglu H. | |
| dc.contributor.author | Atas Y. | |
| dc.contributor.author | Kart P.O. | |
| dc.contributor.author | Yildiz N. | |
| dc.contributor.author | Gumus H. | |
| dc.contributor.author | Aydin K. | |
| dc.contributor.author | Olculu C.B. | |
| dc.contributor.author | Dogan D.E.T. | |
| dc.contributor.author | Per H. | |
| dc.contributor.author | Canpolat M. | |
| dc.contributor.author | Gulec A. | |
| dc.contributor.author | Yildirim N. | |
| dc.contributor.author | Turk E. | |
| dc.contributor.author | Celik N. | |
| dc.contributor.author | Ozturk S. | |
| dc.contributor.author | Kumandas S. | |
| dc.contributor.author | Kilic B. | |
| dc.contributor.author | Topcu Y. | |
| dc.contributor.author | Ozpinar E. | |
| dc.contributor.author | Coskun A. | |
| dc.contributor.author | Arslan M. | |
| dc.contributor.author | Akkoyunlu D.S. | |
| dc.contributor.author | Cine N. | |
| dc.contributor.author | Uzan G.S. | |
| dc.contributor.author | Gunay C. | |
| dc.contributor.author | Akyol D. | |
| dc.contributor.author | Ersoy O. | |
| dc.contributor.author | Direk M.C. | |
| dc.contributor.author | Komur M. | |
| dc.contributor.author | Kirkgoz H. | |
| dc.contributor.author | Karaoğlu P. | |
| dc.contributor.author | Ibis I.B.P. | |
| dc.contributor.author | Cerci C. | |
| dc.contributor.author | Orak A. | |
| dc.contributor.author | Oktay S. | |
| dc.contributor.author | Ayanoglu M. | |
| dc.contributor.author | Yildirim M. | |
| dc.contributor.author | Bektas O. | |
| dc.contributor.author | Serdaroglu E. | |
| dc.contributor.author | Yilmaz S.B. | |
| dc.contributor.author | Cankurt I. | |
| dc.contributor.author | Hirfanoglu T. | |
| dc.contributor.author | Arhan E. | |
| dc.contributor.author | Gencpinar P. | |
| dc.contributor.author | Dundar N.O. | |
| dc.contributor.author | Teber S. | |
| dc.contributor.author | Serin H.M. | |
| dc.contributor.author | Yilmaz S. | |
| dc.contributor.author | Tosun A. | |
| dc.contributor.author | Polat M. | |
| dc.contributor.author | Yilmaz U. | |
| dc.contributor.author | Unalp A. | |
| dc.contributor.author | Kara B. | |
| dc.contributor.author | Okuyaz C. | |
| dc.contributor.author | Yis U. | |
| dc.contributor.author | Hiz S. | |
| dc.contributor.author | Aktan G. | |
| dc.contributor.author | Gokben S. | |
| dc.contributor.author | Unay B. | |
| dc.contributor.author | Serdaroglu A. | |
| dc.contributor.author | Cansu A. | |
| dc.date.accessioned | 2025-04-10T11:01:56Z | |
| dc.date.available | 2025-04-10T11:01:56Z | |
| dc.date.issued | 2024 | |
| dc.description.abstract | Objective: 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. © 2024 British Epilepsy Association | |
| dc.identifier.DOI-ID | 10.1016/j.seizure.2024.09.021 | |
| dc.identifier.uri | http://hdl.handle.net/20.500.14701/43726 | |
| dc.publisher | W.B. Saunders Ltd | |
| dc.title | Therapeutic implications of etiology-specific diagnosis of early-onset developmental and epileptic encephalopathies (EO-DEEs): A nationwide Turkish cohort study | |
| dc.type | Article |