We (Gururaj et al. 2017) described a male child with a severe developmental and epileptic encephalopathy phenotype, with generalised seizures from 3 months of age, evolving to epileptic spasms, who had a rare de novo missense variant in KCNT2. His seizures have continued into childhood and are intractable to multiple antiepileptic medications. Predominant seizure types are prolonged tonic seizures, myoclonic jerk and atypical absences. EEG is persistently abnormal with disorganised background, multifocal epileptogenic activity or hypsarrhythmia. On brain MRI there is white matter thinning, especially in the corpus callosum. Developmental impact is profound, he is nonverbal and non-ambulant.
Subsequently, Ambrosino et al. (2018) reported 2 unrelated females with separate de novo missense variants in KCNT2, and severe epilepsy phenotypes: one had West syndrome which evolved to Lennox Gestaut syndrome and the other had a developmental and epileptic encephalopathy (DEE) with migrating focal seizures. Both children had a rare missense variant affecting the same amino acid residue, Arg190 (p.Arg190His and p.Arg190Pro). Both children’s epilepsy was persistent despite multiple antiepileptic drugs and trial of ketogenic diet. Both children had general developmental delay and moderate to severe intellectual disability. Both can walk unassisted; one is non-verbal and the other can talk in short sentences. The two girls were noted to have subtle distinctive features including bushy eyebrows and long eyelashes with broad mouths.