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22-02-2024 | Valproate | Original Article

Expanding the clinical and genetic landscape of (developmental) epileptic encephalopathy with spike-and-wave activation in sleep: results from studies of a Turkish cohort

Authors: Ayberk Türkyılmaz, Safiye Güneş Sağer, Emine Tekin, Kerem Teralı, Hanife Düzkalır, Metin Eser, Yasemin Akın

Published in: Neurogenetics | Issue 2/2024

Abstract

The terms developmental epileptic encephalopathy with spike-and-wave activation in sleep (DEE-SWAS) and epileptic encephalopathy with spike-and-wave activation in sleep (EE-SWAS) designate a spectrum of conditions that are typified by different combinations of motor, cognitive, language, and behavioral regression linked to robust spike-and-wave activity during sleep. In this study, we aimed at describing the clinical and molecular findings in “(developmental) epileptic encephalopathy with spike-and-wave activation in sleep” (D)EE-SWAS) patients as well as at contributing to the genetic etiologic spectrum of (D)EE-SWAS. Single nucleotide polymorphism (SNP) array and whole-exome sequencing (WES) techniques were used to determine the underlying genetic etiologies. Of the 24 patients included in the study, 8 (33%) were female and 16 (67%) were male. The median age at onset of the first seizure was 4 years and the median age at diagnosis of (D)EE-SWAS was 5 years. Of the 24 cases included in the study, 13 were compatible with the clinical diagnosis of DEE-SWAS and 11 were compatible with the clinical diagnosis of EE-SWAS. Abnormal perinatal history was present in four cases (17%), and two cases (8%) had a family history of epilepsy. Approximately two-thirds (63%) of all patients had abnormalities detected on brain computerized tomography/magnetic resonance (CT/MR) imaging. After SNP array and WES analysis, the genetic etiology was revealed in 7 out of 24 (29%) cases. Three of the variants detected were novel (SLC12A5, DLG4, SLC9A6). This study revealed for the first time that Smith-Magenis syndrome, SCN8A-related DEE type 13 and SLC12A5 gene variation are involved in the genetic etiology of (D)EE-SWAS. (D)EE-SWAS is a genetically diverse disorder with underlying copy number variations and single-gene abnormalities. In the current investigation, rare novel variations in genes known to be related to (D)EE-SWAS and not previously reported genes to be related to (D)EE-SWAS were discovered, adding to the molecular genetic spectrum. Molecular etiology enables the patient and family to receive thorough and accurate genetic counseling as well as a personalized medicine approach.

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Title: Expanding the clinical and genetic landscape of (developmental) epileptic encephalopathy with spike-and-wave activation in sleep: results from studies of a Turkish cohort
Authors: Ayberk Türkyılmaz
Safiye Güneş Sağer
Emine Tekin
Kerem Teralı
Hanife Düzkalır
Metin Eser
Yasemin Akın
Publication date: 22-02-2024
Publisher: Springer Berlin Heidelberg
Keywords: Valproate
Encephalopathy
Clobazam
Epilepsy
Autism Spectrum Disorder
Published in: Neurogenetics / Issue 2/2024
Print ISSN: 1364-6745
Electronic ISSN: 1364-6753
DOI: https://doi.org/10.1007/s10048-024-00751-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Expanding the clinical and genetic landscape of (developmental) epileptic encephalopathy with spike-and-wave activation in sleep: results from studies of a Turkish cohort

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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