GM1 gangliosidosis is an autosomal recessive lysosomal storage disorder caused by a deficiency of β-galactosidase due to pathogenic variants in the GLB1 gene. Almost 300 pathogenic or likely pathogenic variants have been identified, associated with a phenotypic spectrum ranging from GM1 gangliosidosis to mucopolysaccharidosis type IVB. Disease severity is largely determined by the extent to which specific variants impair enzymatic catalytic activity, particularly through disruption of substrate recognition and binding within the active site. We report a patient with GM1 gangliosidosis type I harboring two pathogenic missense variants, c.808T>G (p.Tyr270Asp) and c.808T>C (p.Tyr270His), in a compound heterozygous state. To the best of our knowledge, this specific allelic combination has not been previously described. Both variants affect the same codon, resulting in distinct amino acid substitutions at position 270, a residue critically involved in maintaining the structural and functional integrity of the catalytic domain of β-galactosidase. Disruption at this site is expected to severely compromise enzymatic activity. Comparative analysis with previously reported cases carrying variants at the same residue, in either homozygous or compound heterozygous states, demonstrates a possible consistent association with the infantile form of GM1 gangliosidosis, characterized by a rapidly progressive neurodegenerative course and multisystem involvement. Collectively, these findings provide additional support for the hypothesis that codon 270 can be regarded as a critical functional hotspot within GLB1, where even distinct amino acid substitutions can result in profound enzymatic dysfunction and a severe early-onset phenotype.

Mutations in the IQSEC2 gene cause developmental disorders (OMIM#309530) accompanied by epileptic encephalopathy, movement disorders, dysmorphic facial features, autism spectrum disorders and intellectual disability. The IQSEC2 protein controls excitatory synaptic transmission, regulating responses mediated by glutamate receptors at excitatory synapses, and it is also involved in transmembrane transport, lipid transformation and actin cytoskeleton reorganization, playing an important role in learning processes and memory mechanisms. Polymorphic epileptic seizures that occur at an early age contribute to developmental regression; they are pharma-resistant. The authors describe a clinical case of a patient with drug-resistant epileptic encephalopathy, dysmorphic facial features, autism spectrum disorders, intellectual disability, and absence of speech associated with a hemizygous X-linked de novo mutation in IQSEC2 (chrX:53241815C>T; c.2984G>A; p.Arg995Gln) identified using next-generation sequencing. The use of perampanel as an additional therapy to topiramate made it possible to achieve remission in a patient with focal seizures and bilateral tonic-clonic seizures in combination with other types of seizures (epileptic spasms and tonic seizures).

Tuberous sclerosis complex is an autosomal dominant hereditary disease characterized by the formation of multiple hamartomas in various organs and tissues. Although tuberous sclerosis is considered to be a rare condition, it is among the most common genetic diseases. According to the literature, 16 cases of tuberous sclerosis associated with congenital lymphedema have been revealed from 1984 in scientific publications. Only four of these cases were described in male patients. Such combinations have not been yet described in the Russian studies. The article discusses different aspects of a rare clinical case presented by the combination of tuberous sclerosis with congenital lymphedema in a male patient aged 1 year and 6 months.

The article presents an analysis of the pathogenesis of neurofibromatosis type 1, the mechanism of damage to the central nervous system. It analyzes the general clinical symptoms of neurofibromatosis type 1, its diagnostic criteria, describes the specifics of cognitive development in this disease with an emphasis on behavioral and autism spectrum disorders. The authors describe a clinical case of neurofibromatosis type 1 (a boy, 6 years and 10 months), in which, along with coffee-colored skin spots, subcutaneous fibromas, one of the first symptoms of the disease was also a congenital false joint of the bones of the left leg. Absence of speech development and autism spectrum disorders are key problems in the cognitive status of the child.

Abstract. Introduction. Juvenile myoclonic epilepsy is the most common form of genetic generalized epilepsy, which is included in the group of idiopathic generalized epilepsies. The etiology of drug-resistant forms of juvenile myoclonic epilepsy, which represent a serious clinical problem, is currently a controversial issue. Aim. To reveal the most significant risk factors of resistance in juvenile myoclonic epilepsy. Materials and Methods. The observational retrospective study included 56 patients, 46 (82%) women and 10 (18%) men. Inclusion criteria: patients diagnosed with juvenile myoclonic epilepsy based on the criteria of the International League Against Epilepsy, treatment for at least 2 years. The type and frequency of epileptic seizures, the onset and course of the disease, concomitant diseases, family history, all available results of 1-2 hours video electroencephalographic monitoring with sleep, and magnetic resonance imaging results were analyzed. Depending on the treatment effect, all patients were divided into two groups: 1 – without seizures, 2 – with seizures. Lack of complete seizure control for at least 2 years was considered intractable epilepsy. Risk ratios as outcomes for dichotomous variables in two compared groups for various characteristics and their confidence intervals were calculated using the Review Manager program (v5.3). Differences were considered significant at P<0.05. Results and Discussion. As a result, there were obtained data on the resistance of juvenile myoclonic epilepsy depending on the age of disease onset, the type of epileptic seizures, changes in the electroencephalogram, and the type of antiepileptic treatment. Conclusions. The most significant risk factors of resistance in juvenile myoclonic epilepsy have been identified: frequent generalized tonic-clonic seizures (more than 5 times a year) accompanying the basic disease, depression, anxiety, and lack of response to the treatment with valproic acid. At the same time, non-compliance, sleep disturbances, consumption of alcohol and energy drinks during therapy are factors that can be controlled during the physician’s individual work with the patient aimed at the explanation and prevention of risks in treatment.

The paper analyzes data from scientific publications and presents a clinical case study of a rare genetic epileptic encephalopathy caused by a mutation in the SYNGAP1 gene. The case study focuses on a 4-year-old girl who has been diagnosed with epileptic encephalopathy due to the mutation. The paper describes the anamnesis of the child’s illness, including family history, neurological, neuropsychological, and speech assessments, as well as the results of genetic testing, electroencephalography, and magnetic resonance imaging (MRI). The findings indicate that the main symptoms of the condition are typically epilepsy, autism spectrum disorder, difficulty with phrasal speech, and mental retardation. Common types of seizures include atypical absence seizures, myoclonic seizures, atonic seizures, and eyelid myoclonia with absences. On the electroencephalogram, there is a slowdown in occipital activity and diffuse, prolonged «peak-polypic-slow-wave» complexes. Pathognomonic neuroimaging changes in the brain are typically absent. Valproic acid, levetiracetam, and ethosuximide have been shown to be the most effective treatments for controlling epileptic seizures. Due to the rarity of this syndrome, the authors have provided a detailed clinical case report from their practice.Conclusion. SYNGAP1-related epileptic encephalopathy has a specific clinical presentation, including characteristic EEG findings and a particular pattern of seizures. The diagnostic approach for children with this condition, autism spectrum disorder, and delayed language development should include video electroencephalography with sleep deprivation, as well as genetic testing if necessary, using next-generation sequencing, to ensure early detection and appropriate treatment planning.

Objectives. To assess published data and a series of clinical cases in relation to the clinical features of epilepsy, electroencephalographic changes, and other phenotypic features in X-linked intellectual disability (ID) caused by mutations in the KIAA2022 gene. Materials and methods. Retrospective analysis of medical records from various medical institutions of the Russian Federation was conducted, addressing disease and genealogical histories, , and clinical, genetic, electroencephalographic (EEG), and neuroimaging (brain MRI) investigations. The study included seven clinical cases (five girls and two boys, 5–13 years old) with confirmed diagnoses of X-linked ID due to mutations in KIAA2022 in whom the clinical picture of the underlying disease was combined with epilepsy. Results. The main general phenotypic characteristics of patients with X-linked ID due to KIAA2022 mutations were mental retardation, speech impairment, motor developmental delay, and dysmorphism. The most frequently encountered epileptic seizures were myoclonic and atonic, with nodding, propulsion, atypical absences, and EEG changes showing diffuse “spike– multispike–slow wave” complexes. No pathognomonic brain changes were found on MRI. Antiepileptic therapy was ineffective in many cases. Conclusions. The cases of X-linked ID combined with epilepsy described here indicate that this disease can occur both in males and females and that epilepsy is more often apparent as generalized seizures and in many cases is drug-resistant. More information is needed about this rare genetic syndrome.

Introduction. Early diagnosis of autism spectrum disorder in children is significant clinical problem due to the ever-increasing incidence of this condition in children. Aim. The aim of the study is a comprehensive analysis of data on the features of the bioelectrical activity of the brain in children with autism spectrum disorders, identification of the electroencephalography significance in the diagnosis of these disorders, including the ability to differentiate their subtypes. Material and Methods. The materials for the review were scientific articles indexed in Russian and international databases (Russian Science Citation Index, Scopus, Pubmed) for the period from 1995 to 2022. Results and discussion. The article presents systematized data related to the analysis of electroencephalograms in children with autism spectrum disorder which is carried out in different ways: visual and quantitative. The authors analyzed the changes in the electroencephalograms obtained using spectral analysis, identifying the functional connections of different areas of the brain, with the implementation of non-linear assessment methods. The theory of «mirror neurons» was discussed in connection with the peculiarities of the sensorimotor rhythm reactivity in children with autism spectrum disorder. Conclusion. The presence of electroencephalographic changes in children with autism spectrum disorders is confirmed, especially in the period from 3 to 12 months, although the degree of the sensitivity of methods for their detection at this stage is insufficient for accurate diagnosis. Dynamic electroencephalographic monitoring should be recommended for children with autistic disorders, especially if subclinical epileptiform activity is detected. It is also worth paying attention to the change in functional rhythms in dynamics. In general, results of electroencephalography are often more informative than neuroimaging methods, which in most cases do not reveal organic brain damage in the presence of obvious developmental disorder in a child. The most promising at present are non-linear methods of electroencephalograms analysis.

For integer k≥2 and prime power q, the algebraic bipartite graph D(k,q) proposed by Lazebnik and Ustimenko (1995) is meaningful not only in extremal graph theory but also in coding theory and cryptography. This graph is q-regular, edge-transitive and of girth at least k+4. For its exact girth g=g(D(k,q)), Füredi et al. (1995) conjectured g=k+5 for odd k and q≥4. This conjecture was shown to be valid in 2016 when (k+5)/2 is the product of an arbitrary factor of q−1 and an arbitrary power of the characteristic of Fq. In this paper, we determine all the girth cycles of D(k,q) for 3≤k≤5, q>3, and those for 3≤k≤14, q=3.

The purpose of the research was to study the impact of age on the incidence of disanapsis in children and adolescents with bronchial asthma (BA) taking into consideration the anthropometric features of the patients as well. Materials and methods used: a single-center observational cross-sectional pilot study was conducted with data obtained from 334 patients with atopic BA aged 7 to 17 years old (12.0 [9.0; 14.0] y/o), of which 241 (72.2%) were boys. All of the participants have undergone the spirometry and the diagnostics for disanapsis. Results: the incidence of disanapsis was higher in prepubertal children compared to adolescents, 57.0% (77 of 135) and 30.7% (61 of 199), respectively (p<0.001). These patterns were also typical for children with normal body weight (BW): 53.0% (44 of 83) vs. 22.3% (23 of 103); and for patients with excessive BW: 68.6% (24 of 35) vs. 33.3% (22 of 66) (p<0.001 and p<0.001, respectively). Incidence of disanapsis in patients with obesity was comparable in prepubertal age: 52.9% (9 of 17); and adolescence: 53.3% (16 of 30) (p=0.980). Conclusion: the incidence of disanapsis is higher in prepubertal age than in adolescence in patients with both normal and excessive BW. Incidence of disanapsis is comparable in prepubertal age and adolescence in patients with BA coupled with the obesity.

Background . Alexithymia is traditionally regarded as a factor which influences the development of psychosomatic diseases and contribute to a more severe and prolonged course of somatic diseases the high level of alexithymia indicates the deficit in cognitive processes associated with awareness, exteriorization and regulation of feelings and emotions. In recent years, a lot of research has been conducted on the comorbidity of alexithymia and psychosomatic diseases in adults, but there are very few studies in relation to children and adolescents. The aim . To analyze psychosomatic diseases associated with the high level of alexithymia in adolescents, to study the correspondence of alexithymia and central sensitization (CS) in adolescents with primary headaches (migraine and tension-type headache). Methods . The diagnosis of headache was based on the criteria for the International Classification of Headache, 3rd edition. The study group included 84 adolescents, average age – 14 [13; 16] (51 females, 33 males). CS was assessed using the Russian version of “Central Sensitization Inventory” (2020) for adolescents. Alexithymia was assessed using the Russian version of “Alexithymia questionnaire for children” (2019). Headache intensity was measured using the Visual Analogue Scale. There were also assessed the number of months and days per month with headaches; duration of night sleep; age of phrasal speech start. Results and discussion . The results showed the direct correlation between levels of alexithymia and central sensitization (rS = 0.49; p = 0.00001), the number of days with headaches per month and central sensitization severity (rS = 0.24; p = 0.027). There was no significant correlation between alexithymia severity and headaches duration (rS= 0.06; p = 0.5), no reliable results on the correspondence of alexithymia severity, age of phrasal speech start and nocturnal sleep. Conclusion . A high level of alexithymia is observed in adolescents with various somatic diseases. Primary headaches are associated with a high level of alexithymia and the severity of central sensitization. Pediatricians and neurologists should be advised to assess the level of alexithymia and central sensitization in adolescents with headaches.