Svetlana Ya. Volgina

Familial intrahepatic cholestasis is a heterogeneous group of genetic disorders affecting the secretion and transport of bile acids. Progressive familial intrahepatic cholestasis (PFIC) may debut at different periods of childhood and in adults. Currently, 13 types are known, associated with changes in various genes and extreme phenotypic variability. PFIC2 type is associated with changes in the ABCB11 gene, causing deficiency or dysfunction of the ATP-binding transport protein that excretes bile acids from the hepatocyte into the bile canaliculi against the concentration gradient. Accumulation of bile acids in hepatocytes leads to the development of cholestasis, ranging from transient to fatal progressive familial intrahepatic cholestasis, accompanied by jaundice, growth retardation, liver cirrhosis, liver failure. Timely diagnosis is extremely important for the initiation of therapy to prevent cholestatic liver damage. The presented clinical case demonstrates the possibility of nosological diagnosis of a rare hereditary pathology and the effectiveness of the therapy at this stage. The conducted genetic study allowed us to diagnose familial intrahepatic cholestasis. The clinical phenotype in this patient does not fully correspond to benign recurrent intrahepatic cholestasis type 2 (OMIM # 605479) and PFIC2 (OMIM # 601847), an intermediate phenotype is likely to occur. Dynamic observation and control of clinical, laboratory and imaging characteristics are necessary in order to timely detect disease progression.

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.

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.

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.

BACKGROUND: The preservation and promotion of children’s health remain pivotal aspects of the Russian healthcare. AIM: The study aimed to identify prevalent health patterns among preschool and school-age children in the Novo-Savinovsky district of Kazan between 2018 and 2022. METHODS: The analysis included screening reports from 32 preschool education and care facilities and 20 schools in the Novo-Savinovsky district of Kazan. The reports were provided by medical professionals from the regional child health center and detailed laboratory tests and clinical investigations covering the years 2018 through 2022. In 2018 and 2022, the number of preschool-age children (3–7 years old) examined was 7257 and 6362, respectively. The health status of grade 1–11 students was assessed by analyzing medical statistical data collected between 2018 and 2022. A total of 14,917 and 18,141 schoolchildren were examined in 2018 and 2022, respectively. The population included adolescents aged 15–17 years (2775 and 3841, respectively). A comprehensive health assessment included the distribution of health groups and allocation to special medical groups, physical development, and primary and overall incidence (per 1000 age-matched children). The statistical analysis was performed using StatTech software, with the Mann–Whitney U test used for quantitative variables and the χ2 test used for qualitative variables, with a significance level of p = 0.05. RESULTS: The study period showed a decrease in the proportion of healthy children (p = 0.04) and an increase in the number of preschool children with structural and functional impairments (p = 0.001). The overall incidence demonstrated a 24.3% increase. The most significant increase was observed for respiratory, musculoskeletal, visual, gastrointestinal, and neurological, genitourinary, psychiatric, and behavioral disorders (p = 0.001). Schoolchildren demonstrated a decrease in the proportion of healthy individuals and an increase in the number of children with structural and functional impairments (p = 0.001). The overall incidence decreased by 24.7% (p = 0.001), yet the prevalence of psychiatric disorders (p = 0.03), congenital anomalies, deformities, and chromosomal abnormalities increased (p = 0.0011). The study found a significant increase in school-related diseases throughout the years of school (p = 0.001). CONCLUSION: Between 2018 and 2022, a decline in the overall health of preschool and school-age children in the Novo-Savinovsky district of Kazan was observed, as indicated by a decrease in the proportion of healthy children, an increase in the incidence of structural and functional impairments, and a higher prevalence of school-related diseases.

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.

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.

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.

The issue of autism spectrum disorder (ASD) in children is a significant concern at present. In the Russian Federation, there has been a rapid increase in the incidence of ASD and the number of children diagnosed with this condition, making childhood autism a major medical and social issue. Pediatricians need to be trained in the diagnostic criteria for early identification of this disorder. The main diagnostic methods involve monitoring the child’s development, with the district pediatrician playing a crucial role. The knowledge and expertise of the doctor significantly influences the timeliness of diagnosis and the prescription of appropriate interventions, which can lead to positive outcomes and prevent further symptom progression. It is essential for pediatricians to carefully listen to families’ concerns about any developmental or behavioral issues in their children. According to our research, 32% of families did not receive timely assistance. The most common complaint made by parents was delayed speech development and impaired communication. To identify autism spectrum disorders, doctors should regularly assess a child’s neuropsychiatric development and monitor them in various situations to assess their behavior and interaction with others. If any deviations are detected, a questionnaire such as the M-CHAT (a modified list of questions for detecting autism in children) should be used and the patient referred to a psychiatrist for further consultation. Our study highlighted the need for pediatricians to better understand the signs and symptoms of autism spectrum disorders.