Kanmaz, SedaTekgul, HasanKayilioglu, HulyaAtas, YavuzKart, Pinar OzkanYildiz, NihalAydin, Kursad2025-04-152025-04-152024Kanmaz, 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, 17-25.10591311https://doi.org/10.1016/j.seizure.2024.09.021https://hdl.handle.net/11454/117084Objective: 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.en10.1016/j.seizure.2024.09.021info:eu-repo/semantics/closedAccessEarly-onset developmental epileptic encephalopathiesGenetic testingPrecision medicineStepwise diagnostic modelArticle123Dec1725WOS:0013442534000012-s2.0-8520726674039447234Q2Q2