Features of epileptic encephalopathy caused by SCN1A mutation
Authors: Kyrylova L.G. , Yuzva O.O. , Miroshnikov O.O. , Berehela O.V. 
Published: September 2023

Background. The development and availability of genetic research open both new possibilities in the diagnosis of epileptic encephalopathies and require the search for correlations between detected pathological mutation and the clinical and instrumental examination of a child. In particular, seizure disorders in children in whom SCN1A has been detected cover a spectrum that varies from simple febrile seizures and mild generalized epilepsy with febrile seizures plus, which was first described in 2003, to severe myoclonic epilepsy in infancy (more commonly known as Dravet syndrome) or severe intractable childhood epilepsy with generalized tonic-clonic seizures. Materials and methods. In our study, we examined 4 children (2 boys and 2 girls) with clinical and instrumental signs of epileptic encephalopathy with resistant seizures who were treated in the psychoneurology department for children with perinatal pathology and orphan diseases of the SI “Lukyanova Institute of Pediatrics, Obstetrics and Gynecology named of the National Academy of Medical Sciences of Ukraine”. The average age of patients was 2.20 ± 1.55 years. In addition to the laboratory and instrumental examination, all children underwent a medical genetic analysis (whole exome sequencing or next-generation sequencing) and the mutation of the SCN1A gene was detected. Subsequently, the relationship between the obtained laboratory instrumental and clinical anamnestic data was analyzed using statistical research methods. Results. It should be noted that the onset of genetic disorders caused by SCN1A occurs at the age of 5.5–6 months. During the onset, focal clonic seizures predominate, mainly against the background of hyperthermia, which are later modified into generalized tonic-clonic, myoclonic ones, and even absences. In three of four cases, the epileptiform activity was focal, with a predominant localization in the fronto-central regions followed by generalization. In all children, taking into account the focal onset of attacks, therapy was started with the use of carbamazepine, which is contraindicated in children with this mutation. After analyzing our cases, we saw that the course of the disease and the resistance of attacks were more severe in girls. The study of this phenomenon requires observation of a larger number of children. Conclusions. In children with genetically determined epileptic encephalopathy caused by the SCN1A mutation, the onset of the disease occurs in the first half of life and is usually manifested itself by focal seizures. In children with SCN1A mutation, frontal localization of epileptiform activity prevails. Considering this feature of the disease and based on our own long-term observation of children with epileptic encephalopathies of early age, we would like to warn against the use of carbamazepines in this age group. The course of SCN1A epileptic encephalopathy (Dravet syndrome) is difficult, given the resistance of attacks and regression in the development of a child, and often requires the use of more than 2–3 antiepileptic drugs, but a correctly selected combination allows long-term remission to be achieved.