Objectives. (1) to define the etiologic trend of Developmental Epileptic Encephalopathies (DEE) in the genomic era with a step-based approach in a large cohort between 2005-2021. (2) to evaluate the yields of genetic and metabolic investigations in those without obvious cause after initial clinical phenomenology and magnetic resonance imaging (MRI).
Methods: The study cohort consisted of 1238 patients with DEE from 16 tertiary centers between 2005 and 2021. The most likely specific etiologies were coded by two independent reviewers based on a step-based approach: step I (clinical phenomenology), step II (magnetic resonance imaging-MRI), step III (metabolic screening), and step IV (genetic tests). Etiologic diagnoses were divided into five subgroups according to the ILAE classification: structural, metabolic, genetic, immune-infectious, and unknown.
Results. An etiology specific diagnosis was established 78.8% of patients (976/1238): structural, (n:335, 27.1%); genetic, (n:498, 39.8%); metabolic (n:114, 9.2%); immune-infectious, (n:34, 2.7%) (Table 1). Combined use of the first three steps (I-III) provides a specific diagnosis in 39.9% of children; clinical phenomenology (1.4%) MRI 22.3%, and metabolic screening (16.2%) (Table 2). Since 2014 with the advent of next-generation sequencing (NGS), the diagnostic yield of step IV reached up to 60.2% with the dynamic use of genetic tests with extended variabilities. A new trend was defined for the genetic test preference in the NGS era: WES with %34.3, and epilepsy panels with 25.2% (Table 3).
Conclusion. The presented step-based approachment provided more diagnostic yield and precision therapy implication (33.5%) in children with DEE.
Seda Kanmaz
Ege University Medical Faculty
Turkey
Yavuz Atas
Ege University Medical Faculty
Turkey
Hulya Kayilioglu
Mugla Sitki Kocman University Medical Faculty, Department of Pediatrics, Division of Pediatric Neurology
Cemile Busra Olculu
Ege University Medical Faculty
Turkey
Pınar Ozkan Kart
Karadeniz Technical University Medical Faculty, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Nihal Yildiz
Karadeniz Technical University Medical Faculty, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Betul Kilic
Medipol University Faculty of Medicine
Turkey
Esra Ozpinar
Medipol University Faculty of Medicine, Department of Pediatric Neurology
Turkey
Yasemin Topcu
Medipol University Faculty of Medicine, Department of Pediatric Neurology, İstanbul, Turkey
Turkey
Aysenur Coskun
University of Health Sciences, Gulhane Faculty of Medicine, Gulhane Training and Research Hospital
Turkey
Mutluay Arslan
University of Health Sciences, Gulhane Faculty of Medicine, Gulhane Training and Research Hospital
Turkey
Deniz Sünnetci Akkoyunlu
Kocaeli University Faculty of Medicine, Department of Medical Genetics
Turkey
Naci Cine
Kocaeli University Faculty of Medicine
Turkey
Gamze Sarikaya Uzan
Dokuz Eylul University Medical Faculty, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Cagatay Gunay
Dokuz Eylul University Medical Faculty, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Duygu Aykol
Dokuz Eylul University Medical Faculty, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Ozlem Ersoy
Mersin University Medical Faculty, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Meltem Cobanogulları Direk
Mersin University Medical Faculty, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Mustafa Komur
Mersin University Medical Faculty, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Hatice Hilal Kırkgoz
Pediatric Neurology Clinic, University of Health Sciences Dr. Behçet Uz Child Disease and Pediatric Surgery Training and Research Hospital
Turkey
Pakize Karaoglu
Pediatric Neurology Clinic, University of Health Sciences Dr. Behçet Uz Child Disease and Pediatric Surgery Training and Research Hospital
Turkey
Ipek Burcu Parlak Ibis
Pediatric Neurology Clinic, University of Health Sciences Dr. Behçet Uz Child Disease and Pediatric Surgery Training and Research Hospital, İzmir, Tur
Turkey
Cisil Cerci Kubur
Celal Bayar University Medical Faculty, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Sibgatullah Ali Orak
Celal Bayar University Medical Faculty, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Secil Oktay
Adnan Menderes University Medical Faculty, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Muge Ayanoglu
Adnan Menderes University Medical Faculty, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Mirac Yildirim
Ankara University Medical Faculty, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Omer Bektas
Ankara University Medical Faculty, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Esra Serdaroglu
Turkey
Sema Bozkaya Yilmaz
University of Health Sciences Tepecik Training and Research Hospital, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Ilknur Cankurt
Gazi University Medical Faculty, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Tugba Hirfanoglu
Turkey
Ayten Gulec
Erciyes University Medical Faculty, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Mehmet Canpolat
Erciyes University Medical Faculty, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Huseyin Per
Erciyes University Medical Faculty, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Ebru Arhan
Gazi University Medical Faculty, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Pinar Gencpinar
Izmir Katip Celebi University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Nihal Olgac Dundar
Izmir Katip Celebi University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Serap Teber
Ankara University Medical Faculty, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Hepsen Mine Serin
Ege University Medical Faculty, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Sanem Yilmaz
Ege University Medical Faculty, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Ayse Tosun
Adnan Menderes University Medical Faculty, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Muzaffer Polat
Celal Bayar University Medical Faculty, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Unsal Yilmaz
Pediatric Neurology Clinic, University of Health Sciences Dr. Behçet Uz Child Disease and Pediatric Surgery Training and Research Hospital, İzmir, Tur
Turkey
Aycan Unalp
Pediatric Neurology Clinic, University of Health Sciences Dr. Behçet Uz Child Disease and Pediatric Surgery Training and Research Hospital, İzmir, Tur
Turkey
Bulent Kara
Kocaeli University Medical Faculty, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Cetin Okuyaz
Mersin University Medical Faculty, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Uluc Yis
Dokuz Eylul University Medical Faculty, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Semra Hiz
Dokuz Eylul University Medical Faculty, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Gul Aktan
Ege University Medical Faculty, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Sarenur Gokben
Ege University Medical Faculty, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Bulent Unay
University of Health Sciences, Gulhane Faculty of Medicine, Gulhane Training and Research Hospital, Etlik/Kecioren, Ankara
Turkey
Ali Cansu
Karadeniz Technical University Medical Faculty, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Kursad Aydin
Medipol University Faculty of Medicine, Department of Pediatric Neurology
Turkey
Hasan Tekgul
Ege University Medical Faculty, Department of Pediatrics, Division of Pediatric Neurology
Turkey
