Early Infantile Epileptic Encephalopathy Type 14: Three Cases of Infantile Epilepsy with Migrating Focal Seizures Due to Mutations in the KCNT1 Gene

• Published in: Neuroscience and behavioral physiology 2020-06, Vol.50 (5), p.534-540
• Main Authors: Kholin, A. A., Zavadenko, N. N., Fedonyuk, I. D., Antonets, A. V., Mukhin, K. Yu, Malov, A. G., Vshivkov, M. I., Anisimov, G. V., Il’ina, E. S.
• Format: Article
• Language: English
• Subjects: Amino acid substitution; Amino acids; Behavioral Sciences; Biomedical and Life Sciences; Biomedicine; Chromosome 9; Convulsions; Convulsions & seizures; DNA sequencing; EEG; Encephalopathy; Epilepsy; Hyperemia; Mutation; Neonates; Neurobiology; Neurosciences; Seizures; Serine
• ISSN: 0097-0549; 1573-899X
• DOI: 10.1007/s11055-020-00933-y

Objectives. To study the clinical and electroencephalographic characteristics of early infantile epileptic encephalopathy (EIEE) type 14, due to mutations in the KCNT1 gene. Materials and methods. Over the period 2017–2019, three unrelated girls (M.V. aged three years three months, T.V. aged nine months, and M.U. aged five months) with the clinical picture of infantile epilepsy with migrating focal seizures (IEMFS) were investigated and mutations in the KCNT1 gene were identified. New-generation DNA sequencing (Inherited Epilepsy panel) was run on an Illumina NextSeq 500 platform (USA). Video EEG monitoring was with an Encephalan Video system based on an Encephalan-RM RM-EEG-19/26 instrument (Medikom MTD, Russia). Results and conclusions. M.V. showed a previously undescribed mutation in exon 12 of the KCNT1 gene (chr9:138656907C>T) with amino acid substitution Arg356Trp. T.V. had a known mutation in chromosome 9, 138651532G>A with amino acid substitution of glycine by serine as position 288, i.e., Gly288Ser (OMIM: 608167.0010). M.U. showed a previously undescribed heterozygous mutation in exon 15 of the KCTN1 gene (chr9:138660712A>G), leading to an amino acid substitution in position 480 (Asp480Gly). In M.V., the onset of EIEE was at age four months with hypomotor dialeptic and tonic versive seizures. Epilepsy in T.V. started at age 4.5 months with hypomotor seizures with ophthalmoclonia and facial hyperemia. In M.V., neonatal convulsions were seen with bilateral tonic-clinic seizures and cyanosis, and subsequent development of status epilepticus with alternating hemiconvulsions. All girls went on to develop seizures of multiregional genesis to the level of migrating status epilepticus with the typical electroclinical picture of IEMFS. Thus, these findings lead to the conclusion that the KCNT1 gene may be the main gene determining the development of EIEE.