A novel de novo TET3 loss-of-function variant in a Turkish boy presenting with neurodevelopmental delay and electrical status epilepticus during slow-wave sleep

Sager S. G., TÜRKYILMAZ A., Gunbey H. P., Karatoprak E. Y., Aslan E. S., Akın Y.

Brain and Development, vol.45, no.2, pp.140-145, 2023 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 45 Issue: 2
  • Publication Date: 2023
  • Doi Number: 10.1016/j.braindev.2022.09.004
  • Journal Name: Brain and Development
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, EMBASE, MEDLINE, Psycinfo
  • Page Numbers: pp.140-145
  • Keywords: Electrical status epilepticus during slow-wave sleep, Epilepsy, TET3 gene, Status epilepticus, Treatment, DYNAMICS, TET3
  • Karadeniz Technical University Affiliated: Yes


© 2022 Association for Behavioral and Cognitive TherapiesBackground: Beck-Fahrner syndrome is caused by homozygous or heterozygous mutations in TET3 on chromosome 2p13. The general characteristics of this syndrome include behavioral abnormalities such as autistic features, attention-deficit hyperactivity disorder, learning disabilities, and epilepsy. Case presentation: Six years old male patient was found to have a de novo TET3 loss-of-function variant by whole-exome sequencing (WES) analysis and was diagnosed with electrical status epilepticus during slow-wave sleep (ESES) based on clinical and electroencephalogram (EEG) characteristics. The patient had a neurodevelopmental delay from the age of 3 months and started experiencing generalized tonic–clonic seizures and regression at the age of 5 years. EEG findings were consistent with ESES, and WES analysis revealed a novel heterozygous nonsense NM_001366022.1:c.1594C > T (p.Arg532*) variant in TET3. Valproic acid and immunotherapy were administered for the first 6 months, and clobazam was administered orally in addition to oral valproic acid therapy for the next 6 months. Clinical improvement was noted regardless of EEG improvement for the first 6 months. EEG improvement was achieved with clobazam. No regression was observed following the discontinuation of immunotherapy. Conclusion: Decreased TET3 enzyme activity may be one of the new genetic etiologies of ESES.