Rimma Gabdulbarovna Gamirova

We present a clinical case of a boy with lissencephaly and a pathogenic mutation in the DCX gene, detected by a molecular genetic test using next-generation sequencing (NGS). The clinical presentation, cognitive development features, and results of magnetic resonance imaging of the brain and electroencephalography are described. Also, a systematic review of the clinical, neuroimaging, and neurophysiological features of lissencephaly typical for the DCX gene mutation is provided. The citation databases PubMed and Google Scholar were searched for publications on clinical cases of DCX-associated diseases, and papers were selected according to the PRISMA protocol. The most common clinical symptoms are subcortical band heterotopia, epilepsy, and intellectual disability.

The increasing incidence of speech development disorders is one of the most significant issues in pediatrics and child neurology. The aim of the study . To identify statistically significant differences in the influence of perinatal risk factors on the occurrence of specific and nonspecific speech development disorders. Materials and methods . The longitudinal study included 525 children with specific and nonspecific speech development disorders (324 boys, 201 girls, born between 2005 and 2021). The group with specific speech disorders consisted of 322 children, while the group with comorbid disorders included 203 children. The authors analyzed anamnesis data related to the prenatal and perinatal periods of development, the results of neurological examinations during the first year of life, and their relationship with data on the children's motor and subsequent speech development. A comparative analysis was conducted in the groups. Results . Statistically significant differences (higher incidence in the group with comorbid disorders) were revealed for the following risk factors: in vitro fertilization (p=0.02); threatened miscarriage (pConclusion . Pediatricians and neurologists should be vigilant in identifying these risk factors when assessing the development of a child under three years of age, since they may be harbingers of further delays in psychomotor development, and promptly refer children for neuropsychological diagnostics for the purpose of early intervention in the habilitation process.

GM1 gangliosidosis is a rare autosomal recessive hereditary disorder caused by mutations in the GLB1 gene. The deficient activity of the enzyme β-galactosidase leads to the pathological accumulation of GM1 ganglioside, primarily in the cells of the central nervous system and visceral organs, resulting in progressive neurodegeneration and systemic symptoms. The clinical presentation is highly heterogeneous and can include neurological deterioration, epilepsy, skeletal abnormalities, facial dysmorphism, organomegaly, and ophthalmological manifestations. This clinical polymorphism, along with the variable age of onset and the differing degrees of neurological and systemic involvement, is attributed to the specific mutations and their impact on the residual enzyme activity. Based on this, three types of GM1 gangliosidosis are distinguished: the infantile, juvenile, and late-onset forms. This article reviews current knowledge on the etiology, biochemical defects, pathogenesis, and clinical manifestations of GM1 gangliosidosis. It also analyzes novel potential therapeutic approaches for patients, with insights from animal model studies. While no effective cure for GM1 gangliosidosis currently exists, several strategies show significant promise. The most advanced therapeutic approaches include enzyme replacement therapy, substrate reduction therapy, chaperone therapy, hematopoietic stem cell transplantation, and gene therapy using adeno-associated viral vectors, some of which have already progressed to clinical trials.

Noonan-like syndrome with anagen hair loss is a RAS pathology and is characterized by craniofacial features resembling Noonan syndrome, a spectrum of cardiovascular abnormalities, cognitive deficits and behavioral distorders, short stature usually associated with growth hormone deficiency, a unique combination ectodermal disorders. It results from a missense variant (c.4A>G, c.Ser2Gly) in the SHOC2 gene, located on chromosome 10q25, which encodes a protein that facilitates signaling through the RAS mitogen-associated protein kinase pathway, triggering a number of cellular processes. The prevalence of the syndrome is less than 1 in 1,000,000 (worldwide). Evidence has been obtained that disturbances in the level of expression and activation of the Ras family signaling pathway and its downstream kinases, such as Raf/MEK/ERK1-2, contribute to the pathogenetic mechanisms of the development of autoimmune diseases. Description of a clinical case. We present a previously undescribed clinical case of the development of juvenile arthritis associated with Crohn’s disease in a 13-year-old girl with Noonan-like syndrome with hair loss in the anagen phase. At birth, the patient was diagnosed with a congenital heart defect (multiple atrial septal defect), corrected at 4 years, articular syndrome debuted at 8 years 4 months, intestinal syndrome at 10 years 4 months. Genetic analysis was carried out only at 10 years 7 months, DNA sequencing results were obtained and a pathogenic variant of the nucleotide sequence of the SHOC2 gene was identified in a heterozygous state (c.4A>G, p.Ser2Gly). As a result of the analysis of clinical data, laboratory and instrumental studies, a diagnosis was made: “Juvenile arthritis (pauciarticular variant) associated with Crohn’s disease (ulcerative bauginitis, ulcerative ileitis, catarrhal jeunitis, aphthous left-sided colitis, erosive gastritis). Noonan-like syndrome with hair loss in the anagen stage 1. Hypopituitarism. Partial growth hormone deficiency. Condition after ASD repair.” The girl received treatment: a course of glucocorticosteroids (methylprednisolone) with gradual withdrawal, methotrexate, adalimumab and mesalazine with positive dynamics. Conclusion. Pediatricians need to remember the possibility of developing autoimmune diseases in children with NPS, the need for their early diagnosis, timely referral to specialists and adequate therapy.

Introduction. Post-stroke anxiety, depression, and pain are relevant to medical practice, since they represent a significant obstacle to the effective rehabilitation of patients. Information related to post-stroke anxiety and depression is analyzed in the literature, data on the level of central sensitization (CS) which also indicates the presence of comorbid disorders are insufficient. Furthermore, such studies have not been conducted in samples of native speakers of various languages of the Russian Federation until recently due to the lack of diagnostic tools in these languages. Aim. To compare the levels of СS, anxiety, and depression in patients after ischemic stroke in the early recovery period, using the same instrument in different languages in comparable samples. Materials and methods. The authors analyzed the level of CS, anxiety, and depression in 4 groups. Study groups: 1) Russian-speaking patients who had suffered ischemic stroke (30 people, early recovery period); 2) Tatar-speaking patients who had suffered ischemic stroke (30 people, early recovery period). Comparison groups: 1) Russian-speaking informants without neurological deficit (30 people); 2) Tatar-speaking informants without neurological deficit (30 people). The Central Sensitization Inventory (CSI, Russian and Tatar versions) and the Hospital Anxiety and Depression Scale (HADS, Russian and Tatar versions) were used to assess the level of CSI, depression, and anxiety. Results. Analysis of CSI data revealed statistically significant differences between the study and comparison groups in the subclinical CS parameter. Among stroke patients, the subclinical variant of CS is less common than in healthy controls; clinically significant variants predominate. Statistically significant differences were found in HADS anxiety subscale and HADS depression subscale for both the Russian-speaking and Tatar-speaking study and comparison groups. Conclusion. The data were obtained in samples of native speakers of different languages; the results are comparable, which confirms the universality of the diagnostic scales CSI and HADS for use in the diagnosis of anxiety, depression and CS in post-stroke patients.

Cat eye syndrome is a rare genetic pathology characterized by the presence of an additional small supernumerary marker chromosome formed from copies of a region of chromosome 22, resulting in partial tetrasomy. However, Cat eye syndrome cases with partial or complete trisomy of chromosome 22 are also reported. This article presents descriptions of three atypical clinical cases of the syndrome, one of which is comorbid by epilepsy, and therefore its description is more detailed. The clinical picture of these three cases did not include the classic triad of the syndrome. Current study provides new information on possible variants of the Cat eye syndrome phenotype, including comorbidity with epilepsy, and contributes to the formation of a database that allows for a detailed and comprehensive study of the Cat eye syndrome.

Neurofibromatosis type 1 is a multisystem genetic disorder characterized by the development of benign and malignant tumors, among which plexiform neurofibromas occupy a special place. These tumors, which occur in 10–30% of patients, significantly impair the quality of life, causing pain, disfigurement and functional impairment. Traditional treatment of plexiform neurofibromas was limited to surgical intervention, but the possibility of radical resection of tumors exists only in a small number of patients. The use of the selective MEK inhibitor selumetinib has opened a new stage of therapy for inoperable plexiform neurofibromas. Clinical studies demonstrate a significant reduction in tumor volume (68% of patients showed a partial response with long-term improvement) and improvement in clinical symptoms, such as pain and motor impairment. Despite predominantly mild or moderate toxicity, the most common adverse events included skin reactions, gastrointestinal disorders, and increased creatine phosphokinase levels, requiring careful monitoring and timely correction. The introduction of selumetinib into clinical practice has significantly changed the approach to managing patients with neurofibromatosis type 1, allowing for effective control of plexiform neurofibromas growth, improving the quality of life of patients, and minimizing the need for repeated traumatic surgical interventions. However, further study of optimal doses, duration of treatment, and monitoring of adverse events during targeted therapy of inoperable plexiform neurofibromas in children with neurofibromatosis type 1 is required.

The review summarizes the data on Noonan-like syndrome with loose anagen hair (NSLH) from the group of RASopathies. The genetic aspects of the syndrome, its pathogenesis, clinical signs, and comorbitant conditions are considered. Particular attention is paid to the differential diagnosis between two genetically heterogeneous types of NSLH associated with mutations in the SHOC2 gene (NSLH1) and in the PPP1CB gene (NSLH2). Clinical case description of the patient with confirmed NSLH1 is presented. This review is intended to increase physicians’ awareness specifically on NSLH genotype-phenotype correlations. This is crucial for genetic counseling, diagnosis, and development of new management and rehabilitation methods.

The chapter considers issues of sleep ontogenesis from the prenatal period to adolescence and the neurobiological basis of changes in the structure of sleep as the brain matures, including the neurophysiological features of sleep in newborns, sleep state organization in premature infants, and the importance of fetal/neonatal rapid eye movement sleep for brain development and plasticity. It describes: (а) the dynamics of changes in sleep structure, (b) EEG specificity at different age periods, (c) sleep-related behavioral features in children, (d) biomarkers of normal and abnormal brain function, and (e) the pathophysiology of various childhood sleep disorders.

Noonan-like syndrome with anagen hair loss is a RAS pathology and is characterized by craniofacial features resembling Noonan syndrome, a spectrum of cardiovascular abnormalities, cognitive deficits and behavioral distorders, short stature usually associated with growth hormone deficiency, a unique combination ectodermal disorders. It results from a missense variant (c.4A>G, c.Ser2Gly) in the SHOC2 gene, located on chromosome 10q25, which encodes a protein that facilitates signaling through the RAS mitogen-associated protein kinase pathway, triggering a number of cellular processes. The prevalence of the syndrome is less than 1 in 1,000,000 (worldwide). Evidence has been obtained that disturbances in the level of expression and activation of the Ras family signaling pathway and its downstream kinases, such as Raf/MEK/ERK1-2, contribute to the pathogenetic mechanisms of the development of autoimmune diseases. Description of a clinical case. We present a previously undescribed clinical case of the development of juvenile arthritis associated with Crohn’s disease in a 13-year-old girl with Noonan-like syndrome with hair loss in the anagen phase. At birth, the patient was diagnosed with a congenital heart defect (multiple atrial septal defect), corrected at 4 years, articular syndrome debuted at 8 years 4 months, intestinal syndrome at 10 years 4 months. Genetic analysis was carried out only at 10 years 7 months, DNA sequencing results were obtained and a pathogenic variant of the nucleotide sequence of the SHOC2 gene was identified in a heterozygous state (c.4A>G, p.Ser2Gly). As a result of the analysis of clinical data, laboratory and instrumental studies, a diagnosis was made: “Juvenile arthritis (pauciarticular variant) associated with Crohn’s disease (ulcerative bauginitis, ulcerative ileitis, catarrhal jeunitis, aphthous left-sided colitis, erosive gastritis). Noonan-like syndrome with hair loss in the anagen stage 1. Hypopituitarism. Partial growth hormone deficiency. Condition after ASD repair.” The girl received treatment: a course of glucocorticosteroids (methylprednisolone) with gradual withdrawal, methotrexate, adalimumab and mesalazine with positive dynamics. Conclusion. Pediatricians need to remember the possibility of developing autoimmune diseases in children with NPS, the need for their early diagnosis, timely referral to specialists and adequate therapy.