A novel de novo TET3 loss-of-function variant in a Turkish boy presenting with neurodevelopmental delay and...

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.

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.

Decreased TET3 enzyme activity may be one of the new genetic etiologies of ESES.