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Background. Prion diseases or transmissible spongiform encephalopathies are a group of neurodegenerative disorders characterized by rapidly progressive dementia and movement disorders. Prion diseases can be acquired, sporadic, genetic (inherited), and are characterized by the accumulation and aggregation of prions or abnormally coiled proteins. The diseases have a long incubation period (years) but progress rapidly after the manifestation of clinical symptoms. The most common human prion diseases are sporadic in nature. Prion diseases include sporadic Creutzfeldt – Jakob disease, as well as rare cases of sporadic fatal insomnia and variable protease-sensitive prionopathy. The diseases have a long incubation period (years), but progress rapidly after the manifestation of clinical symptoms. Fatal familial insomnia (Insomnia, fatal familial; OMIM: # 600072) is a rare autosomal dominant neurodegenerative disease with high penetrance and associated with mutation in PRNP gene.Results. The article presents clinical case of 15-year-old patient with severe mental development disorder, motor excitability, hyperactivity of sympathetic nervous system and insomnia. The previously described variant in PRNP gene (D178N) was detected by whole exome sequencing. Validation of the mutation in the proband and segregation analysis were carried out: mutation c.532G>A, Asp178Asn in PRNP gene was identified in the proband and his 50-year-old father, who had no signs of prion disease. at the time of the study. Additionally, adenine in the 358th position was found in a homozygous state, which is responsible for the frequent M129M polymorphism in Sanger sequencing of PRNP gene in the proband and his father.Conclusion. The description of the clinical case of fatal familial insomnia in Russia presented by the authors clearly shows the likely difficulties that doctors may face when examining such patients. The diagnosis (clinical, genetic using massively parallel sequencing methods) remains important in relation to medical genetic counseling and family planning, since methods of pathogenetic therapy for hereditary prion diseases have not currently been developed.

PACS1 neurodevelopmental disorder (Schuurs-Hoeijmakers syndrome; MIM #615009) is a rare autosomal dominant genetic syndrome characterized by developmental delay, intellectual disability, dysmorphic features, and rare seizures. The article describes a clinical case of PACS1 syndrome in a female patient with developmental delay, speech disorder, motor development delay and epilepsy coupled to described variants in PACS1 gene (rs398123009, chr11:6621120, c.607C>T, p.Arg203Trp). Knowing PACS1 syndrome molecular mechanisms is important not only for genotype-phenotypic correlation, but also for developing new therapeutic approaches that could improve the quality of patients’ life.

In most cases, variants of nucleotide sequence in the SEMA6B gene account for developing the phenotype of progressive myoclonus epilepsy and, to a lesser extent, developmental encephalopathy with or without epilepsy. Loss-of-function variants in nucleotide sequence localized mainly in exon 17 of the SEMA6B gene contribute to production of aberrant proteins with “toxic” functions. A clinical case of status epilepsy in a patient with a variant in the SEMA6B gene (c.2506delС; p.His836ThrfsTer136; NM_032108.4) is described in the article that expands our knowledge regarding the SEMA6B gene variants resulting in progressive myoclonus epilepsy.

Focal epilepsy is the most common type of epilepsy accounting for 60–70% of all cases of this pathology. We present two familial cases of focal epilepsy associated with a nucleotide sequence variant in DEPDC5 gene. Clinical and ancestry examination was performed by using instrumental (magnetic resonance imaging, video-electroencephalography) and genetic testing methods. The nucleotide sequence variants in DEPDC5 gene were found in two probands and paired fathers with epilepsy. Focal cortical dysplasia was detected only in the father of Proband 1 as well as Proband 2 with resistant epilepsy and severe cognitive deficit. Hence, such clinical cases confirm that pathogenic variants in DEPDC5 gene are related with familial focal epilepsy, which clinical manifestation may depend on the type of identified mutation. The study of genotype-phenotype correlations is necessary to apply proper therapy. Before surgical treatment of epilepsy, the genetic testing by whole exome or whole genome sequencing should be performed.

The review presents the results of clinical studies of the efficacy and safety of Tenoten and Tenoten children’s in the treatment of anxiety, neurotic, stress-related and somatoform disorders and adjustment disorders. Technologically processed antibodies to the S100 protein in Tenoten and Tenoten children’s drugs change the conformation of the S100 protein, which is considered as a pathological link in the development of anxiety states, as well as neurodegenerative diseases. Tenoten is a well-studied daytime anxiolytic that combines a favorable safety profile with high anxiolytic activity. The efficacy of Tenoten in the treatment of anxiety disorders is comparable to that of benzodiazepine drugs. Tenoten has no inhibitory and muscle relaxant effects, does not cause drug tolerance, addiction, "withdrawal" syndrome, as well as drug interactions. Tenoten for children has been shown to be effective in the treatment of anxiety in children, including those with somatic manifestations, attention deficit hyperactivity disorder, and learning disabilities.

The article presents the clinical cases of 6 patients with epilepsy, psychomotor and speech developmental delay. The heterozygous variants of the nucleotide sequence in SPTAN1 gene were detected by whole exome sequencing. Mutations in SPTAN1 gene have been described in patients with developmental and epileptic encephalopathy 5 (ОMIM: 613477). The clinical history, electroencephalographic and magnetic resonance imaging data of our patients are similar in children with variants in SPTAN1 gene described previously. It was shown that variants in SPTAN1 gene located closer to the C-terminal region are associated with a more severe phenotype, whereas the variants near the N-region – with a milder course of the disease without structural brain anomalies. However, further research is necessary in the future to better understand genotype-phenotypic correlations in SPTAN1-associated encephalopathy.

The clinical case of a patient with congenital contractures of the lower and upper limbs, face, seizures, facial dysmorphias, motor disorders and psychomotor development delay is presented. The proband with Freeman–Sheldon syndrome had no mutations in genes associated with distal arthrogryposis. Chromosomal microarray analysis revealed terminal duplication of the long arm of chromosome 9 and terminal microdeletions of the short arm of chromosome 20 – 46,XX.arr[hg38]9q33.3q34.3 (127016168_138124666) x3,20p13 (259113_1003183)x1 in the de novo status. This clinical observation demonstrates an opportunity of using innovative molecular cytogenetic technologies in the search for disease-related genetic causes in the absence of mutations detected by whole exome sequencing.