Autosomal dominant sleep-related hypermotor epilepsy associated with a novel mutation of KCNT1

Abstract

Autosomal dominant sleep-related hypermotor epilepsy (ADSHE) is characterized by severe sleep-related rigid hypermotor seizures. The pathogenic genes of ADSHE include genes encoding subunits of the neuronal nicotinic acetylcholine receptor, KCNT1, DEPDC5, NPRL2/3, CABP4, and CRH. Individuals with KCNT1-related ADSHE are more likely to develop seizures at a younger age, have cognitive comorbidity, and display psychiatric and behavioral problems. In this study, a 12-year-old Chinese girl was referred for genetic evaluation of grand mal seizures. She had paroxysmal convulsions of the limbs and loss of consciousness just after falling asleep without obvious triggers. A novel heterozygous missense mutation c.2797C > T (p.Arg933Cys) in exon 24 of the KCNT1 was identified in the proband by whole-exome sequencing and Sanger sequencing, and the clinical symptoms were compatible with ADSHE. The proband’s father has been showing similar symptoms for more than 20 years and had the same site mutation. Her mother and sister were physically and genetically normal. The study revealed a novel variant in the KCNT1 and expanded the mutation spectrum for this clinical condition. Our results provide further evidence supporting a causative role in KCNT1 variants in ADSHE.

Efficacy of anti‐seizure medications and alternative therapies (ketogenic diet, CBD, and quinidine) in KCNT1‐related epilepsy: A systematic review

“…A benefit was also observed in 37.5% (3/8) of cases with clobazam (“most often reported to be effective” for the 3 patients 4 ) and 50% (3/6) with oxcarbamazepine (“most often reported to be effective” for 2 patients, 4 and controlled seizures for the last one 15 ).…”

“…CBD without precise details about the formulation (n = 5). 4,15 Among the 8 patients treated with Epidyolex ©, the effect of treatment was reported in only 3, with a benefit in one out of three (dosage of 25 mg/kg/day, initiation at 3.9 years, and follow-up over several years, with an impression of a decrease in seizure intensity, but no change in frequency). 11 One patient experienced digestive side effects (diarrhea and vomiting) 30 and another observed an increase in seizures frequency.…”

Fearful arousals in sleep terrors and sleep-related hypermotor epileptic seizures may involve the salience network and the acute stress response of Cannon and Selye

“…In one night, several seizures emerge, contrasting the rare DOA events. A somewhat dubious aspect is the age-distribution of the two spectra: DOA typically accumulate in childhood and manifest a descending age-slope to adulthood and older age [27] ; this may be similar, but is certainly less clear in SHE [28] , [29] .…”

Could Neonatal Electroclinical Syndromes Orchestrate Diagnosis and Treatment?

“…¾ KCNT1-DEE presents with focal tonic seizures and autonomic symptoms [18,[44][45][46]. ¾ BRAT1-DEE is an autosomal recessive disorder characterized by hypertonia, arthrogryposis, and spontaneous, nonepileptic, and multifocal myoclonus over a relatively organized EEG background.…”