[Epileptic encephalopathy associated with a mutation in the KCNT1 gene]

According to the World Health Organization, more than 50 million people worldwide have epilepsy, and about 5 million new cases are reported annually. According to other data, the number of patients exceeds 70.000.000, highlighting the relevance of this condition. Studies of developmental epileptic encephalopathies leading to early disability are particularly relevant. About 900 gene mutations associated with different types of epilepsy have been identified so far. One of the prominent «channelopathy genes» representatives is KCNT1, coding the largest subunit of the sodium-activated potassium channel, KNa1.1. Its mutations are associated with many neurological disorders, such as leukodystrophy, leukoencephalopathy, West syndrome, Ohtahara syndrome, early myoclonic encephalopathy, focal epilepsy, and multifocal epilepsy. A clinical case of a typical course of KCNT1-associated epilepsy with early onset (in the first half of life), focal and asynchronous paroxysms, psychomotor retardation, and drug resistance is presented. The effectiveness of the anticonvulsants used and the nature of pharmacological resistance were analyzed. The applicability of four «Drug Resistance Hypotheses» to this case is shown: genetic, since the pathogenesis of this particular case is based on a change in the properties of potassium channels; a change in the sensitivity of the anticonvulsant targets explains the intermittent (according to Schmidt and Löscher) nature of resistance. The «Neural Networks Hypothesis» is illustrated by the change of encephalographic indicators from multifocal epileptiform activity with an intact background to pronounced dysrhythmia with periods of the «burst-suppression» pattern after several months. All these features, combined, refer to the «Intrinsic Severity» hypothesis by Rogawski and Johnson, since the child's disease was initially severe due to the intensity and frequency of epileptic seizures. As a result, a conclusion was made about the complexity of the refractoriness formation mechanisms, even in cases with a simple and understandable pathogenesis of channelopathy.