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<p>Data from the World Health Organization show that epilepsy affects more than 50 million people worldwide and approximately five million are diagnosed annually. Other sources place the number of patients at over 70 million, which determines and will continue to determine the relevance of research on this topic. Research into developmental epileptic encephalopathies, which lead to early disability, is particularly relevant. Approximately 900 genes in which a variety of mutations explain the development of different types of epilepsy have been identified to date. One prominent example of “channelopathy genes” is <i>KCNT1</i>, which specifies the largest subunit of the sodium-activated potassium channel, KNa1.1. Mutations in this gene are associated with a wide range of neurological disorders, such as leukodystrophy, leukoencephalopathy, West syndrome, Ohtahara syndrome, early-onset myoclonic encephalopathy, focal epilepsy, and multifocal epilepsy. A clinical case of typical <i>KCNT1</i>-associated epilepsy with early onset (in the first half of life), focal and asynchronous paroxysms, psychomotor retardation, and drug resistance is presented. The efficacy of the antiepileptic drugs (AED) used for treatment and the nature of pharmacological resistance are analyzed. The applicability of four hypotheses of drug resistance to this case is demonstrated: the genetic hypothesis, as the pathogenesis of this particular case was based on changes in the properties of potassium channels; the target hypothesis explains the intermittent nature of resistance in terms of changes in the sensitivity of the targets of AED action; the neural network hypothesis is illustrated by the dynamics of encephalographic parameters, from multifocal epileptiform activity with an unaltered background to severe dysrhythmia with periods of the burst-suppression pattern after a number of months. All these features taken together relate to the intrinsic severity hypothesis of Rogawski and Johnson, as the child’s disease was initially severe due to the intensity and frequency of the epileptic seizures. The observations led to the conclusion that the mechanisms of formation or drug resistance are complex even in cases with a simple and understandable pathogenesis of channelopathy.</p>

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Epileptic Encephalopathy Associated with a Mutation in the KCNT1 Gene

  • 期刊论文

  • 发表日期：

    2026年3月20日

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  • P. L. Sokolov,
  • N. V. Chebanenko,
  • Yu. A. Fedotova,
  • D. M. Mednaya

摘要

Data from the World Health Organization show that epilepsy affects more than 50 million people worldwide and approximately five million are diagnosed annually. Other sources place the number of patients at over 70 million, which determines and will continue to determine the relevance of research on this topic. Research into developmental epileptic encephalopathies, which lead to early disability, is particularly relevant. Approximately 900 genes in which a variety of mutations explain the development of different types of epilepsy have been identified to date. One prominent example of “channelopathy genes” is KCNT1, which specifies the largest subunit of the sodium-activated potassium channel, KNa1.1. Mutations in this gene are associated with a wide range of neurological disorders, such as leukodystrophy, leukoencephalopathy, West syndrome, Ohtahara syndrome, early-onset myoclonic encephalopathy, focal epilepsy, and multifocal epilepsy. A clinical case of typical KCNT1-associated epilepsy with early onset (in the first half of life), focal and asynchronous paroxysms, psychomotor retardation, and drug resistance is presented. The efficacy of the antiepileptic drugs (AED) used for treatment and the nature of pharmacological resistance are analyzed. The applicability of four hypotheses of drug resistance to this case is demonstrated: the genetic hypothesis, as the pathogenesis of this particular case was based on changes in the properties of potassium channels; the target hypothesis explains the intermittent nature of resistance in terms of changes in the sensitivity of the targets of AED action; the neural network hypothesis is illustrated by the dynamics of encephalographic parameters, from multifocal epileptiform activity with an unaltered background to severe dysrhythmia with periods of the burst-suppression pattern after a number of months. All these features taken together relate to the intrinsic severity hypothesis of Rogawski and Johnson, as the child’s disease was initially severe due to the intensity and frequency of the epileptic seizures. The observations led to the conclusion that the mechanisms of formation or drug resistance are complex even in cases with a simple and understandable pathogenesis of channelopathy.