Dravet and Dravet-like syndromes

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Introduction. Dravet syndrome, previously called severe myoclonic epilepsy of infancy, is a complex form of genetic epilepsy that was first described in France in 1978. Since the myoclonic component is not always present in the symptoms and there is some variability, the name was changed to Dravet syndrome in 1989 [4].

The genetic etiology of this syndrome was discovered in 2001, and since then numerous studies have contributed to a better understanding of this disease. About 70% of patients carry a mutation in the alpha subunit of the SCN1A gene.  In addition to mutations in the SCN1A gene (alpha subunit of the sodium channel mapped on chromosome 2q24), mutations in other genes were also detected. Thus, syndromes characterized by similar clinical manifestations, but caused by mutations in other genes, were called Disease-like.[6],[7].

At the moment, there are more than 12 of them, and all of them are inherited in an autosomal dominant type. Thus, genetic epilepsy with febrile seizures plus, which includes Dravet and Dravet-like syndromes, is characterized by locus heterogeneity. [5],[6],[8].Dravet-like syndromes include: borderline severe myoclonic epilepsy of infancy (SMEB), intracurable childhood epilepsy with generalized tonic-clonic seizures (ICE-GTC), severe infantile multifocal epilepsy (SIMFE), X-linked epileptic encephalopathy associated with the PCDH19 gene, Dose syndrome – epilepsy with myoclonic-atonic seizures and focal epilepsy with febrile seizures plus (FEFS+) [5].

A reliable confirmation of Dravet and Dravet-like syndromes is the conduct of genetic counseling, namely, exome sequencing using the panel "hereditary epilepsies". Untimely treatment leads to significant developmental delay, impaired cognitive functions such as speech, memory, attention, and pyramidal insufficiency, which prompted us to conduct a study [4].

The purpose of the work. To identify the pathological genetic variants associated with febrile seizures. Evaluate the genetic polymorphism.

Materials and methods of research. A retrospective study of patients with febrile seizures hospitalized in PNO1 in VODKB No. 1 in the period from 09/20/2010 to 06/30/2024 was conducted.

Patients with a history of febrile seizures were selected.Inclusion criteria: current febrile seizures or a history of febrile seizures, informed parental consent for inclusion in the study.

Exclusion criteria: absence of febrile seizures, inflammatory diseases of the nervous system, neurodegenerative progressive diseases of the nervous system.

Statistical processing of the obtained data was carried out using Microsoft Excel 2019, STATISTICA6.0., using methods of variational statistics for parametric data with the calculation of average values of indicators (M). The difference between the compared values was recognized as statistically significant with an error probability of p <0.05.

The results of the study. The number of patients diagnosed with febrile seizures is 58. Of these, the number of patients with a confirmed mutation in the SCN1A gene (Dravet syndrome) is 7 patients, which is 12%. In the course of the conducted studies, it was found that the average age of onset in patients with confirmed Dravet syndrome was 10.8 months. The maximum age of the debut was 2.5 years, the minimum age was 4.5 months. Cognitive functions were reduced in 100% of patients at the time of examination. Pyramidal insufficiency (ataxia) was also present in 100% of patients (Figure 1).

Figure 1 "Number of confirmed mutations among all patients"

Confirmed Dravet-like seizures were registered in 6 patients, which is a percentage of 10%.  Of these, 1 patient had a mutation in the HNRPUN de novo gene, 1 patient had a missense mutation described as RME type 31, 1 patient had a heterozygous variant in the SYNGAP1 gene, 1 patient had a GRIA3 mutation, 1 patient had exome sequencing using the hereditary epilepsy panel RAII, described in Smith syndrome-Magnisa, 1 patient has a mutation in the SCN8A gene. The analysis revealed the average age of onset in patients with confirmed Drave–like syndromes - 1 year and 2 months (Figure 2). The maximum age of the debut was 2.5 years. The minimum is 5 months. Cognitive functions were reduced in 100% of patients at the time of examination. Pyramidal insufficiency (ataxia) in 100% of patients.

Figure 2 "Age of debut"

Similar clinical manifestations were found in patients of both groups, such as an early age of onset of the disease, regression of cognitive functions associated with the age of onset – 100% in both groups, and pyramidal insufficiency (ataxia) – 100% in both groups. This, in turn, leads to early disability of patients. Currently, one of the most important priorities of neurologists is the timely diagnosis of Grave and Grave-like syndromes based on a number of characteristic features, followed by the appointment of necessary therapy and genetic counseling.

Conclusion. The genetic polymorphism of Dravet and Dravet-like syndromes was studied and similar clinical manifestations were identified, such as the early age of onset of the disease, regression of cognitive functions associated with the age of onset, and pyramidal insufficiency (ataxia). All of the above indicators are indications for the NGS genetic examination (according to the panel of hereditary epilepsy) for the appointment of further therapy.

About the authors

Anastasia Andreevna Lopatina

Voronezh State Medical
University named after N. N. Burdenko

Author for correspondence.
Email: lopatina220anasta@gmail.com
ORCID iD: 0000-0001-8665-4846

student,Faculty of Medicine

Russian Federation, 10 Studencheskaya str., Voronezh, 394036, Russia

Ekaterina Igorevna Sheshnikova

Voronezh State Medical
University named after N. N. Burdenko

Email: catherine.sheshnikova@yandex.ru
ORCID iD: 0009-0009-1503-2164

student,Faculty of Medicine

Russian Federation, 10 Studencheskaya str., Voronezh, 394036, Russia

Nataliya Alexandrovna Ermolenko

Voronezh State Medical
University named after N. N. Burdenko

Email: ermola@bk.ru
ORCID iD: 0000-0001-7197-6009

Head of the Department of Neurology, Professor

10 Studencheskaya str., Voronezh, 394036, Russia

References

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