Developmental and epileptic encephalopathies in children: clinical, neurophysiological, neuroimaging and genetic characteristics

Background. The purpose of the study to analyze the clinical, neurophysiological, neuroimaging and genetic characteristics of young children with developmental and epileptic encephalopathy and to determine risk predictors for the development of autism spectrum disorders, with the aim of forming a cohort of children in need of dynamic monitoring and early intervention. Materials and methods. Thirty-eight children aged 0–3 years with developmental and epileptic encephalopathy were included in the study. The examination included assessment of neurological status, history taking, assessment of semiology and determination of seizure type, assessment of development and screening for autism spectrum disorders at the age of 18 and 24 months, video-EEG monitoring during night sleep, magnetic resonance imaging of the brain, screening for pathogenic variants by whole exome sequen-cing. Results. A feature of this group of disorders is the presence of subtle, often unrecognized epileptic seizures, which are manifested by persistent focal (60.5 %) or generalized (31.6 %) activity with medium (55.3 %) or high (15.8 %) index of spike-and-wave activity during the stage of slow sleep and the amplitude emphasis over the frontal (52.6 %) or temporal (28.9 %) lobes. According to magnetic resonance imaging, structural changes in the brain were found in 91.1 % of children, including focal or diffuse changes in the white matter of the brain in 36.8 %, hypoplasia of the corpus callosum in 21.1 %, atrophic changes in the cerebral cortex in 15.8 %, congenital malformations in 13.2 % of cases. Pathogenic variants of 35 different genes were found in the examined children with the onset of seizures during the first year of life. Pathogenic variants of genes responsible for the synthesis and repair of DNA and RNA (28.9 %) and the activity of intracellular enzymes were the most common — 8 cases (21.1 %). The share of children with general developmental delay at the age of 24 months was 11.9 %, and cognitive impairment — 34.2 %. Conclusions. It was shown that children with a history of generalized tonic-clonic seizures (RR = 2.13) had a high risk of developing autism spectrum disorders at 24 months. A positive relationship was found between the presence of mutations in genes responsible for DNA synthesis and repair (RR = 1.88) and an increased risk of developing ASD at the age of 24 months (90.9 % of children).