Clinical and genetic characteristics of young children with epileptic encephalopathies and their role in the development of autism spectrum disorders

Abstract

Purpose - to analyze the clinical and genetic characteristics of young children with developmental and epileptic encephalopathies and to determine their role in the formation of autism spectrum disorders (ASD). Materials and methods. The study included 58 children aged 0-3 years with the onset of epileptic seizures in the first year of life, clinical manifestations of developmental and epileptic encephalopathies with genetic etiology. The examination included assessment of neurological status, collection of anamnesis, assessment of semiology and determination of seizure type, assessment of development and screening for ASD at the age of 18 and 24 months, night sleep electroencephalography (video EEG), brain magnetic resonance imaging (MRI), screening for pathogenic variants by whole-exome sequencing or examination of relevant gene panels. Pathogenic variants of 33 different genes were found in the examined children. Pathogenic variants of genes responsible for the function of ion channels (41.3%), intracellular signaling systems (17.2%), organelles and intracellular membranes (12.1%) were most frequently found. 44.8% of children had symptoms of ASD at the age of 18 months, and 68.9% of children at the age of 24 months. The predominant types of epileptic seizures were myoclonic (37.9%) and focal clonic (34.4%). According to video EEG monitoring, interictal focal (39.6%) and multifocal (22.4%) epileptiform changes dominated in the examined children. According to MRI, structural changes of the brain were found in 86.2% of children. Conclusions. It is shown that children with a history of myoclonic seizures (RR=1.264) and infantile spasms (RR=1.44) have a high risk of developing ASD at 24 months. It has been established that there is a positive relationship between the presence in the child of mutations in the genes responsible for the functioning of ion channels (RR=1.32), as well as for the functioning of synapses, neurotransmitters and receptors (RR=1.5) and the development of ASD in 24 months. The research was carried out in accordance with the principles of the Declaration of Helsinki. The research protocol was approved by the Bioethics and Deontology Commission. Informed consent of the children’s parents was obtained for the research. No conflict of interests was declared by the authors.