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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.

This article presents a clinical case of Gerstmann–Sträussler–Scheinker syndrome (GSS) – a progressive inherited prion disease with an extremely rare phenotype that changed dynamically during the course of the disease and eventually led to the misdiagnosis of a motor neurone disease. An important feature of this case is a progressive myelopathy, probably due to the deposition of prion protein plaques, with the development of symptoms of lower motor neuron involvement (muscle atrophy, areflexia, fasciculations and muscle hypotonia). Clinical, laboratory, electrophysiological and neuroradiological features of this case are presented. The final diagnosis was verified by whole-exome sequencing – a typical mutation p.P102L in the prion protein gene PRNP was identified. It is discussed whether GSS should be included in the differential diagnosis in patients with progressive motor disorders, a family history and unchanged long nerve conduction function according to electromyography.

The article presents a description of the family case of rare hereditary prion disease – Gerstmann–Sträussler–Scheinker syndrome with a verified p.P102L mutation in the PRNP gene. The clinical picture was represented by progressive cerebellar ataxia, pyramidal signs, bulbar syndrome, and neuropathy, which made it possible to establish a preliminary diagnosis of autosomal dominant spinocerebellar ataxia. Subsequently, the final diagnosis was verified using the massive parallel sequencing technology. The features of this observation are the variable age of onset within the family, with the unusually early age of the disease onset in the proband (age of 25 years), the absence of cognitive impairment, as well as the absence of pathological changes in the electroencephalography and brain MRI study. The possible modifying role of polymorphism in codon 129 of the PRNP gene (129Val) in the disease phenotype formation, as well as the clinical findings and diagnostic methods of this syndrome are discussed.

Fatal familial insomnia (FFI) is a rare genetic human prion disease with an autosomal dominant pattern of inheritance caused by a D178N mutation in the PRNP gene. FFI is characterized by a variable clinical presentation and subacute manifestation. The latter prompts to consider autoimmune encephalitis as a differential diagnosis in the diagnostically challenging patients. Here, we present a clinical case of FFI that was initially misdiagnosed with autoimmune encephalitis. A 26-year-old woman presented with rapid development of diverse neurological features, autonomic and endocrine disturbances, which initially were considered as manifestations of an autoimmune disease due to the lack of clear indications of positive family history. She was started on corticosteroids with temporary stabilization and even with a mild improvement for several months. Progressive deterioration of her symptoms with development of the psychiatric and cognitive impairment, as well as subsequently received additional information regarding positive family history, prompted us to perform a PRNP gene test that revealed a D178N mutation and confirmed an FFI diagnosis.

Gerstmann-Sträussler disease (GSD) is a very rare autosomal dominant late-onset neurodegenerative disorder related to prion protein gene PRNP . Mutation p.Pro102Leu produces about 80% of cases, which are often named GSD-102. DNA testing provides exact diagnosis. In the presented Russian family there were 3 patients: a female index case, age 32 years, her brother, age 37 years (age of onset in both is 27 years) and their deceased father (onset in 35 years, death in 44 years). GSD was not suspected until whole exome sequencing in the female detected PRNP mutation p.Pro102Leu confirmed in her and in the brother by Sanger sequencing. Atypical features of the case are: early onset in siblings, absence of mental and behavioral problems in the female and in the father and mild disturbances in the brother; epilepsy in the brother; atypical onset with transient signs in the brother. Other intrafamilial differences are prevailing spastic paraparesis in the female in contrast to predominant ataxia in the brother and dysarthria absence in the female. The case illustrates GSD-102 variability, complicating clinical diagnostics.