Responsibility of medical professionals has been discussed with varying degrees of intensity for many years among healthcare professionals and in the media. The established practice of holding a medical professional accountable when claims are received from patients and their legal representatives in the event of unfavorable treatment outcomes indicates that the guilt of a specialist in most cases is determined by his or her actions or inactions. The authors give arguments and discuss that, along with errors that occur directly to the medical professional, there are factors that influence the outcome of the treatment, including those caused by the characteristics of the patient himself, which cannot be foreseen and which generally remain unknown to the society.

   The review describes the mechanism of T2 inflammation and its relationship with chronic polypous rhinosinusitis. The authors conducted a search and systematization of data on the treatment of polypous rhinosinusitis using monoclonal antibodies that act on various biomarkers, and touched upon the problem of local IgE inflammation in the nasal mucosa.

   Proximal spinal muscular atrophy 5q is an autosomal recessive neuromuscular disease. This disorder is characterized by progressive symptoms of flaccid paralysis and muscular atrophy due to degeneration of α-motor neurons in the anterior horns of the spinal cord. The disease is caused by the lack of a fully functional SMN protein due to homozygous deletion of exon 7 in the SMN1 gene. For a long time, spinal muscular atrophy was the leading genetic cause of infant mortality. With the introduction of modern pathogenetic treatment methods that modify the disease, the duration and quality of life of patients increases, and a “blurring of boundaries” between types of spinal muscular atrophy and the formation of new phenotypes happens. In this regard, approaches to patient management, including approaches to the assessment and correction of respiratory disorders, are changing. The review of the available medical literature was conducted. The clinical studies on spinal muscular atrophy in the natural course of the disease and with the use of pathogenetic drugs were analyzed, as well as the data on the state of the respiratory system of the patients.

   Currently, there is a large number of studies indicating that preterm infants have reduced levels of T-receptor and kappa-deletion recombination excision rings (TREC and KREC) as indicators of impaired T- and/or B-cell immunity. Studies aimed at in-depth study of the causative factors that led to the decrease in the estimated indicators remain relevant.

   Purpose. Determination of the influence of somatometric parameters and prenatal factors on the level of TREC and KREC in newborns, as well as evaluation of the dynamics of these indicators from gestational age.

   Material and methods. The study included 203 neonates with gestational ages ranging from 22 to 41 weeks. TREC and KREC were isolated by PCR from dried blood spots on Guthrie cards. Blood sampling was performed as part of neonatal screening. The estimated parameters were analyzed according to gestational age, somatometric data and prenatal factors (mode of delivery, number of fetuses in pregnancy). Statistical analysis was performed using the StatTech v. 4.1.4 software.

   Results. It was found that the increase in gestational age by 1 week increases the KREC level by 44.610·105 (rxy = 0.271, p < 0.001), TREC level by 27.274·105 (rxy = 0.264, p = 0.002). Linear regression analysis showed weak direct relationships between TREC and KREC levels and anthropometric data. Children from multiple pregnancies had significantly higher TREC values than infants from singleton pregnancies (p < 0.001).

   Conclusion. The immune system of premature newborns is capable of producing adequate amounts of TREC and KREC. Between 22 and 28 weeks of age, the most intense increase in the assessed indicators occurs, after which their levels relatively stabilize. Since TREC and KREC levels tend to decrease in preterm newborns, a comprehensive evaluation of the dynamics of these indicators depending on significant prenatal and somatometric data is extremely important.

   Currently, oxidative stress is considered as one of the most important factors in the pathogenesis of many pathological processes occurring in the newborn baby.

   Purpose. To establish the relationship of the polymorphism of genes, encoding antioxidant enzymes (glutamyl cysteine ligase, manganine superoxide dismutase) with unfavorable neurological outcomes in preterm children at various age periods.

   Material and methods. A prospective cohort continuous study included 151 preterm children, with a gestational age of 26–32 weeks and body weight of 590–1990 grams. Cord blood was sampled in children to determine allelic polymorphisms of 4 genetic markers: the SOD2 gene rs4880 (с.47C>Т, р.Ala16Val), the SOD2 gene rs1141718 (с.58T>C, р.Thr58Ile), the SOD2 gene rs11575993 (с.60С>Т, р.Leu58Phe), GCLC gene rs17883901 (с.–129 С>Т). The division of children into groups was carried out based on the assessment of neurological outcomes at the following control points: 1 control point — at the time of discharge from hospital, 2 control point — corrected age of 1 year of life, 3 control point — 4 years of life.

   Results. The cohort of children with unfavorable neurological outcomes was found to increase from 36.4 % at the time of hospital discharge to 70 % by the age of 4 years. Children who joined the cohort of children with unfavorable neurological outcomes at corrected age of 1 year of life were carriers of 47 CT of the gene of the mitochondrial superoxide dismutase (SOD2) rs4880, and those, attached by 4 years of age, were carriers of heterozygous 129 CT genotype of the gene of the catalytic subunit of glutamate cysteine ligase (GCLC) rs17883901 and 47 CT mitochondrial superoxide dismutase (SOD2) rs4880. Children with a favorable neurological outcome at corrected age of 1 year of life were more often diagnosed with homozygous 47 CC genotype of SOD2 rs4880 and 60 CC SOD2 rs11575993, and at the age of 4 years of life — with homozygous 129 CC genotype of GCLC rs17883901 gene and 47 TT
SOD2 rs4880.

   Conclusion. The study of single nucleotide exchange in the antioxidant enzyme genes will establish the risk group of children exposed to free-radical injuries of CNS and begin neuroprotective therapy with the inclusion of antioxidant treatment.

   Abstract. Diseases of the nervous system, among which perinatal lesions of the central nervous system and their consequences, occupy a leading place in the structure of morbidity and disability in infants of the first year of life. An urgent clinical task is to search for new objective criteria for the effectiveness of ongoing treatment and rehabilitation measures in patients who suffered perinatal lesions of the nervous system.

   Purpose. To assess the dynamics of postural control indicators during the postneonatal medical habilitation in infants with impaired motor development, born at different gestational ages.

   Material and methods. We examined 64 infants of the first year of life with impaired motor development, born at different stages of gestation (main group) and 16 healthy full-term infants (control group). Patients of the main group were divided into 4 subgroups: 1^st (n = 16) were extremely premature, 2^nd (n = 16) — moderately premature, 3^rd (n = 16) — late preterm and 4^th (n =  16) — full-term infants. The examination was conducted at 3–4 months of calendar (for full-term) and corrected (for premature babies) age and included a clinical assessment of postural control and computer stabilography, which were conducted before and after completion of the course of medical habilitation.

   Results. The severity of the dynamics of postural control indicators in infants of different gestational ages with impaired motor development was different and was maximum in very premature patients.

   Conclusion. The identified features of the dynamics of clinical and functional indicators in infants of the studied subgroups indicate the prospect of further development of objective criteria for assessing the effectiveness of treatment and habilitation measures. Their use will help ensure a personalized approach to the management of patients with motor development disorders and increase the effectiveness of medical habilitation.

   The development of personalized medicine is inextricably linked with the study of the patient’s genetic profile, which determines not only the features of the course of the disease, but also the risks of its occurrence.

   Purpose. The aim of the work was to study possible associations between the genetic polymorphisms GSTT1, GSTM1, NAT2 and predisposition to the development of acute lymphoblastic leukemia in children of the East Siberian region.

   Material and methods. A total of 82 children with acute lymphoblastic leukemia and 227 healthy volunteers with no history of hematological pathology were examined. Deletion polymorphisms in the glutathione S-transferase GSTT1 and GSTM1 genes were detected by polymerase chain reaction (PCR) with electrophoretic detection of amplification products in agarose gel; the type of acetylation was determined by genotyping SNP rs1495741 of the NAT2 gene by conducting a polymerase chain reaction in real time. The material for the study was DNA samples isolated from buccal epithelium samples.

   Results. Statistical processing allowed us to draw the following conclusions: the rate of acetylation of xenobiotics does not affect the risk of acute lymphoblastic leukemia in children of the Caucasian ethnic group of the East Siberian region.

   Conclusion. There is no associative relationship between deletions in the GSTM1 and GSTT1 genes and the risk of developing acute lymphoblastic leukemia in children of the Caucasian ethnic group of the East Siberian region. It was found that the risk of developing acute lymphoblastic leukemia in children was significantly higher with the variant of combinations of alleles of the rapid type of NAT2 acetylation and normal activity of GSST1 and GSTM1 (G/G, active, active).

   The relevance of the problem of hereditary cystic kidney diseases (cystosis) is due to the wide variability of the renal phenotype and the genotype that determines the prognosis, the progression to renal failure as early as in childhood.

   Purpose. To present the results of the analysis of the correlation of genotype and phenotype, renal function in isolated cystic kidney diseases with an autosomal recessive type of inheritance in children.

   Material and methods. in 14 children (from 13 families) aged 9 months — 17 years, the features of the clinical phenotype of kidney cysts with autosomal recessive type of inheritance and gene mutation were evaluated according to the results of a molecular genetic study.

   Results. In 3 (23 %) of 13 families, the family history is burdened by kidney cysts. The characteristic of gene mutation in cystic kidney diseases with autosomal recessive type of inheritance in 13 patients is presented (in 2 tables). Of the 21 identified variants in the genes PKHD1, INVS, NPHP1, TMEM67, 15 (71 %) had known pathogenic significance, 6 (29 %) had previously undescribed variants in data-bases. Variants of the PKHD1 gene were identified in 11 children with the phenotype of polycystic kidney disease with autosomal recessive type of inheritance and liver fibrosis. In the study, variant C.107C>T (Thr36Met) is the most common among children with identified variants of the PKHD1 gene in autosomal recessive polycystic kidney disease in 5 out of 21 (23.8 %), c.664A>G (Ile222Val) in 1 (4.8 %), c.6992T>A (Ile2331Lys) in 1 (4.8 %), c.10444C>T (Arg3482Cys) at 1 (4.8 %). Infantile (n=1) and juvenile (n = 2) nephronophthysis were confirmed in 3 children with homozygous and compound heterozygous pathogenic variants in the INVS, NPHP1, TMEM67 genes.

   Conclusion. The features of the genotype and phenotype are presented in 14 children with autosomal recessive type of inheritance of isolated kidney cysts in autosomal recessive polycystic kidney disease (n = 11) and nephronophthysis (n = 3), of whom chronic kidney disease was established in 13 children aged 2–17 years: in 4 (30.8 %) C1, in 4 (30.8 %) C2, in 3 (23 %) C3, in 1 (7.7 %) C4, in 1 (7.7 %) C5.

   Despite the significant effectiveness of steroid therapy, specialists face serious difficulties in managing patients with steroid-dependent nephrotic syndrome, which requires the prescription of immunosuppressive therapy. Among the available adjuvant drugs, mycophenolate mofetil stands out as a preferred option due to its safety profile, good tolerability, and high efficacy. Currently, only a few studies are presented in the literature on the effectiveness of the use of mycophenolic acid in children with nephrotic syndrome, which is explained by the complexity of the pharmacokinetics of the drug.

   The article presents the results of a study whose purpose was to evaluate the value of determining mycophenolic acid in patients with steroid-dependent nephrotic syndrome to maintain stable clinical and laboratory remission of the disease.

   The study examined 78 patients aged 1 to 18 years with steroid-dependent nephrotic syndrome. The results demonstrated that determination of mycophenolic acid concentrations in children with steroid-dependent nephrotic syndrome is an effective method for monitoring therapy for nephrotic syndrome in aunts. Determining the concentration of mycophenolic acid at the C0 point is a highly specific and sensitive method for predicting the development of relapses of the disease, while a mycophenolic acid concentration level of more than 3.2 μg/ml can serve as a minimum guideline for monitoring the use of mycophenolic acid in children with steroid-dependent nephrotic syndrome.

   Diseases of the urinary system in children are a pressing problem due to the development of chronic kidney disease.

   Purpose. To identify predictors of the development of chronic kidney disease in young children, develop a treatment and rehabilitation complex and evaluate its effectiveness based on the dynamics of structural and functional disorders of the urinary system.

   Material and methods. 69 children (14.5 ± 9.6 months) with aged kidney diseases and 35 children (11.7 ± 5.9 months) of the control group without kidney disease were examined.

   Results. 76.1 % of children have chronic secondary pyelonephritis, their likelihood increases if the mother has a history of pathology of the placenta the blood and digestive organs; when these are combined with gestational diabetes mellitus, there are relationships with congenital hydronephrosis, pyelocalicectasia, vesicoureteral reflux, with a reliability of the model of 86 %. Relationships between VEGF-A and urinary syndrome, indicators of renal blood flow in children with unfavorable maternal medical history factors were found.

   Conclusion. Somatic pathology, diseases of the placenta and gestational diabetes mellitus in the mother’s history increase the likelihood of pathology of the urinary system and are associated with hydronephrosis, pyelocalicoectasia, vesicoureteral reflux in children. VEGF-A levels may be markers of an unfavorable or favorable course of pyelonephritis. 26 % of children with secondary pyelonephritis require surgical correction. The complex, including antibiotics, calcium metabolism regulators, diuretics of plant origin (Canephron N), physiotherapy, influenced the restoration of the structures and functions of the kidneys.

   Literary data on the speech status of children with congenital heart defects are presented. The results of a study of word-formation function in adolescents after radial correction of septal congenital heart defects are described.

   Purpose. To assess the speech status of adolescents operated on for congenital heart defects using the example of word formation.

   Material and methods. A prospective study of the word-formation function of 37 adolescents in the early postoperative period after radical correction of septal heart defects under artificial circulation was conducted at the Research Institute of Complex Problems of Cardiovascular Diseases.

   Results. The most difficult task was the formation of diminutive nouns. The respondents completed this task with a score of 55.31 %. Teenagers coped better with tasks on the formation of different categories of adjectives. Score of the task of forming relative adjectives — 60.54 %. The children coped with the task of forming possessive adjectives even more successfully — by 63.24 %. The respondents were most successful in completing the task of forming qualitative adjectives — by 81.44 %.

   Conclusion. Despite successful cardiac surgery, patients require interdisciplinary monitoring in the postoperative period.

   Parenti–Migno neurodevelopmental disorder is a rare syndromal form of intellectual disability in children, associated with the CHD5 gene, the prevalence of which is not established. Currently, 16 patients with this pathology have been described. CHD5 belongs to the conservative family of chromatin remodeler proteins, is part of the histone deacetylase NuRD complex, and is crucial for the early differentiation of neurons in the central nervous system and acts as a tumor suppressor. Recently, thanks to the application of whole-exome sequencing, the association of this gene with Parenti–Migno neurodevelopmental disorder was first described in patients with developmental delay, psycho-neurological disturbances, facial phenotype features, and skull pathology. We present a unique case of the disease associated with a new variant p.Arg1521Thr in the CHD5 gene, in a girl with intellectual and neurological impairments, craniofacial dysmorphism, as well as previously undescribed symptoms such as cleft lip and palate, hydrocephalus, and renal pathology. The cause of the disease was determined through whole-genome sequencing, which highlights the value of this method in the diagnosis of undifferentiated forms of intellectual disabilities.

   Multilocus imprinting disturbances (MLID) is a molecular subtype of imprinting disorders (IDs), in which multiple methylation abnormalities of imprinted regions and genes are observed in combination with polymorphic clinical manifestations, including overlapping phenotypic features of individual imprinting disorders. The causes of MLID are mutations in genes encoding oocyte and zygotic factors of embryo development, which increases the risk of recurrent birth of children with imprinting disorders in mothers carrying such mutations. Due to the need to understand the exact risk for repeated childbirth, it is advisable to diagnose MLID in patients with an ambiguous phenotype and a negative result of studies on individual imprinting disorders, followed by a search for mutations in MLID-associated genes.

   The purpose of the work is to describe the clinical and epigenetic characteristics of a patient with MLID.

   A clinical case of a comorbid patient aged 12 years with an established molecular genetic diagnosis of MLID by the method of methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) is presented. The features of the patient’s phenotype allow us to demonstrate the effect of hypomethylation of several differentially methylated regions of imprinted genes on the formation of a polymorphic phenotype, including overlapping signs of individual imprinting disorders, and to assess the difficulty of making an unambiguous clinical diagnosis for this patient. Pronounced clinical polymorphism, negative results of previously conducted molecular genetic studies on certain forms of imprinting disorders allow us to consider the MLID study as a first-line test for the diagnosis of methylation abnormalities in MLID and imprinting disorders.

   Klinefelter syndrome is one of the most common chromosomal abnormalities and the most common genetic cause of male infertility. About 85 % of patients have 47,XXY karyotype, other patients have other non-mosaic and mosaic Klinefelter syndrome variants. We report a unique clinical case — Klinefelter syndrome patient with double Y autosomal translocation. The proband is a 15-year-old male patient (height 180 cm, weight 50 kg, normal IQ) who was admitted for cytogenetic examination and genetic counseling due to delayed puberty. He was diagnosed with testicular hypoplasia, hypergonadotropic hypogonadism, pituitary microadenoma and left-sided varicocele. The proband was born in a nonconsanguineous marriage after in vitro fertilization due to paternal male factor infertility. Cytogenetic analysis was performed on cultured peripheral blood lymphocytes using standard chromosome analysis with GTG staining and FISH analysis. Molecular analysis of the Y chromosome was performed by multiplex PCR. Complex cytogenetic examination revealed a 46,XX,der(Y) t(Y;15)(q12;q11.1),der(13)t(Y;13)(q12;p11.2),-15 karyotype in the proband. Molecular analysis showed that the proband is SRY positive; no microdeletion of the Y chromosome was found. The detected double Y autosomal translocation is a chromosomal abnormality independent of KS. The father of the proband is an oligozoospermic man with robertsonian translocation 13;15 — 45,XY,der(13;15)(q10;q10), the mother has a normal karyotype 46,XX. Apparently, the der(13) and der(Y) chromosomes result from abnormal meiotic recombination in paternal meiosis between the heterochromatic region Yq12 and the centromeric/pericentromeric heterochromatin of chromosomes 13 and 15 involved in the paternal robertsonian translocation, and Klinefelter syndrome is due to the presence of two X chromosomes in the karyotype in the presence of a derivative Y chromosome. The detected double Y-autosomal translocation is a chromosomal abnormality unrelated to Klinefelter syndrome, arising on the background of the paternal robertsonian translocation.

   Anaphylaxis is a serious allergic reaction that is life-threatening. Insect anaphylaxis is diagnosed in one in 10 patients with anaphylaxis. Timely treatment and a clear algorithm of tactics to manage the condition can save the patient’s life. Diagnostics and properly selected recommendations will bring more understanding of the principles of exclusion of future reactions. This article presents data on the prevalence, clinical manifestations, diagnosis and treatment of patients with insect anaphylaxis. A clinical case of wasp sting anaphylaxis is also presented.

   Vitamin D is an important component of immune function, and deficiency in childhood is associated with an increased risk of acute respiratory viral infections.
   Purpose. To assess the dynamics of vitamin D supply in children after a new coronavirus infection with the use of cholecalciferol.

   Material and methods. We examined 55 children aged 0–17 years (10.0 [9.2; 10.6] years), 52.7 % boys with COVID-19, who received cholecalciferol in a dose of 1000 to 3000 IU for 30 days in depending on the concentration of 25(OH)D. After 30 days of taking vitamin D3, the levels of total vitamin D in the blood serum were re-determined.

   Results. The median 25(OH)D level in children with COVID-19 was 24.5 [23.9; 26.7] ng/ml. 34.5 % of children had vitamin D deficiency status (≤ 20 ng/ml), 32.7 % had insufficiency (21–30 ng/ml), a third of patients had normal vitamin D status (≥ 30 ng/ml). As a result of treatment with cholecalciferol, the number of children with hypovitaminosis D decreased by 2 times (35.4 %, p < 0.05), with an adequate level — doubled (65.5 %, p < 0.05). Depending on the level of 25(OH)D, no statistically significant differences were found in the severity of coronavirus infection (χ² = 0.872, p = 0.929).

   Conclusion. In 2/3 of cases, children infected with SARS-CoV-2 had hypovitaminosis D. Children under 6 years of age were more likely to have vitamin D insufficiency, while patients 7–17 years of age had a deficiency. The distribution of vitamin D levels did not differ depending on the severity of coronavirus infection. Doses of cholecalciferol taken for 30 days were sufficient to increase the concentration of vitamin D in the blood serum of children with deficiency but did not reach standard values in patients with vitamin D deficiency.

   The aim of the study is to show the application of the case method for studying diagnosis of rare diseases on a specific example.

   The article presents the possibilities of virtual diagnosis of a clinical case — a child with congenital hypothyroidism complicated by fever of unclear genesis. The authors presented a web application that allows reproducing the process of differential diagnosis in order to clarify the genesis of prolonged subfebrile fever. At each stage of virtual diagnosis, a user is supposed to analyze all the information about the patient and make a decision: plan further examination, «refer» the patient to specialists for consultations, while forming diagnostic hypotheses. As a result of passing the case, the integral score — the sum of points for correct answers — is calculated and displayed on the screen. Repeated performing of virtual diagnosis usually increases the score, and, most importantly, helps to consolidate the knowledge necessary for correct diagnosis. Interactive clinical case can be used in the training process of clinical residents, medical students as an additional tool. It can also be applied for pediatricians’ professional upgrade for they can be exposed to this pathology. Application of case method in education allows to guide the learning physician through the stages of virtual diagnosis, to evaluate the accuracy of his decisions and to explain the mistakes made while solving the case.