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

Türkyılmaz A., Sağer S. G., Tekin E., Teralı K., Düzkalır H., Eser M., ...Daha Fazla

NEUROGENETICS, cilt.11, sa.10, ss.1-10, 2024 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 11 Sayı: 10
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1007/s10048-024-00751-1
  • Dergi Adı: NEUROGENETICS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Biotechnology Research Abstracts, MEDLINE
  • Sayfa Sayıları: ss.1-10
  • Karadeniz Teknik Üniversitesi Adresli: Evet

Özet

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.