Hypertrophic cardiomyopathy is the leading cause of sudden cardiac death in children and adolescents, which in most cases is caused by life-threatening arrhythmias. The article highlights the main risk factors and problems of preventing sudden cardiac death in children with hypertrophic cardiomyopathy. The modern problems of stratification of the risk of sudden cardiac death in children based on the assessment of risk factors and multifactorial mathematical models of risk are considered. The clinical, functional and genetic markers of the risk of sudden death in children in comparison with the adult population are considered. Indications for cardioverter defibrillator implantation for the prevention of sudden death are presented and its effectiveness is evaluated.

The last weeks of pregnancy are a critical period of intrauterine development of the central nervous system. In late preterm infants born at gestational age 340/7 — 366/7 weeks, the maturation of the central nervous system continues postnatally, which determines its high vulnerability to various pathologic effects. Morphofunctional immaturity and frequent complications of the neonatal period increase the likelihood of early brain lesions leading to further disorders of neuropsychiatric development. Even in the absence of clinically significant neurological abnormalities in the neonatal period, late preterm neonates have a risk of social-adaptive, behavioral, motor and cognitive impairments in later life. Predicting the outcome of central nervous system lesions in late preterm neonates is possible with the help of neuroimaging methods, as well as with the use of specialized tools to assess various areas of psychomotor development. Modern approaches to prevent neurological complications include prevention and treatment of hypoxia, hypoglycemia, hyperbilirubinemia, infections, provision of adequate nutritional support and adherence to vaccination in late preterm neonates.

The literature review presents current concepts of the pathogenesis, features of phenotype, course, and prognosis of orphan disease — generalized arterial calcification of infancy, type 1 due to mutation of the ENPP1 gene and type 2 due to mutation in the ABCC6 gene. The published results of clinical observations confirmed the effectiveness of bisphosphonate therapy in pediatric patients with generalized arterial calcification of infancy type 2. The enzyme replacement therapy with recombinant ENPP1, which can prevent arterial calcification and intima proliferation, reduce hypertension and mortality in an experiment on mouse models of ENPP1 deficiency, is promising.

There is currently an increase in the number of patients diagnosed with autism spectrum disorders due to the broad interpretation of the criteria for this diagnosis and an actual increase in the number of children with impaired communication and behavioral functions. There are different in their cause, but clinically similar conditions that are attributed to this group. However, the difference in pathogenetic causes may require different approaches to treatment — selection of pharmacological and pedagogical methods of therapy and rehabilitation of these clinical conditions.

In this article, we plan to discuss possible causes of idiopathic (primary) autism spectrum disorders complex, i.e., when there is no indication that the child has conditions or diseases that may lead to the autism spectrum disorders symptom complex (syndromal autism): perinatal disorders, microanomalies of brain structures, sluggish infections (e.g., CMV infection with smoldering encephalitis), and autoimmune brain damage, chromosomal and genetic diseases with an identified gene with pathogenic significance. When discussing autism spectrum disorders or autism without the above conditions, a genetic model is also assumed, but with the inclusion of a large number of candidate genes, without specifying a clear contribution of each gene to pathogenicity.

Numerous studies show that the mechanism of these disorders in autochthonous disease is related to the disruption of synaptic transmission, changes in the ontogenesis of the nervous system in the context of combinations of genetic disorders, as well as the resulting mechanisms of autoinflammatory changes in the structures of the central nervous system. Changes in the permeability of the hematoencephalic barrier, inflammation and disturbance of the glymphatic system are also considered as probable mechanisms of autism spectrum disorders pathophysiology. As a result of impaired synaptogenesis, differentiation and neurogenesis, the resulting excitotoxicity of neurotransmitters and their metabolites, reliably contribute to the formation of the maintenance of this process.

X-linked Alport syndrome is multisystem disease caused by mutation in COL4A5. Aortic dilatation described in X-linked Alport syndrome is considered a specific manifestation of the disease.

Purpose. To define prevalence and risk factors for aortic dilatation in boys with X-linked Alport syndrome.

Methods. Retrospective cross-section single center study included boys with X-linked Alport syndrome (n=67, age 10.2±4.6), comparison group consisted of boys with congenital urinary tract abnormalities (n=20, age12.2±4.8). All patients underwent on clinical-laboratory examination and echocardiography. Aorta was measured in the parasternal long-axis view at level of the sinus of Valsalva, aortic dilatation was determined by z-score >2 for BSA.

Results. The prevalence of sinus of Valsalva dilatation did not differ between two groups (0.1 vs 0.15; p=0.47). The sinus of Valsalva dilatation was associated with body mass index (p=0.019), left ventricular diastolic diameter (p=0.01) and left ventricular mass (p=0.01) in children with congenital urinary tract abnormalities, with body mass index (p=0.02) and left ventricular diastolic diameter (p=0.03) in boys with Alport syndrome. No statistically significant effect of blood pressure level, proteinuria, eGFR and type of COL4A5 mutation on aortic dilatation has been demonstrated.

Conclusion. The prevalence of aortic dilatation in boys with X-linked Alport syndrome is higher than in general population, but comparable to children with congenital urinary tract abnormalities. The body mass index and left ventricular diastolic diameter were associated with aortic dilatation in Alport syndrome males. We did not show the relationship between blood pressure load, proteinuria, eGFR and aortic dilatation. Study limitations: small sample size, prevalence of young patients with chronic kidney diseases stage 1–2 and missense mutations in the COL4A5 gene.

Pregnancy in patients with CKD is associated with maternal and fetal risks.

Purpose. To evaluate course and outcome of pregnancy in Alport syndrome women.

Material and methods. Single-center retrospective study included 88 women with genetically confirmed disease. The information about clinical data at conception, course of pregnancy, delivery (preterm delivery <37 gestation weeks; early preterm delivery <34 gestation weeks), fetus characteristics (intrauterine fetal growth restriction: height <2 z-score for gestation age; small for gestation age: weight <2 z-score) were obtained from medical charts and a cross-sectional survey of women.

Results. Information about 117 term pregnancies (2 — in 26, 3 — in 3 patients) was obtained. The 1/3 of women (q=0.37) had complications of pregnancy: proteinuria (q=0.23), blood hypertension (q=0.1), threat of miscarriage (q=0.21). Preterm and early preterm delivery were seen in 1/4 of women (q=0.26), including early preterm in 3% of cases. Intrauterine fetal growth restriction and small for gestation age were recorded in 9% and 11% neonates, respectively; 7% of babies required a neonatal intensive care unit stay. Proteinuria was the risk factor for preeclampsia (OR=42.35 3±1.1; p<0.001), preterm delivery (OR=11.8±0.5; p<0.001), intrauterine fetal growth restriction (OR=12.2±0.7; p<0.001), small for gestation age (OR=7.2±0.6; p<0.001).

Conclusion. The risk of preeclampsia and fetal growth restriction in women with Alport syndrome and normal kidney function appears comparable to that in the general population. But the disease should be considered as a potential risk factor for preterm delivery. Proteinuria is associated with unfavorable pregnancy and fetal outcome in Alport syndrome.

Neonatal Marfan syndrome (ORPHA:284979) is a severe form of the syndrome that manifests in infancy and rapidly progresses in childhood. The causative variant of the disease is most often localized in exons 24–32 of the FBN1 gene, in the so-called “neonatal region.” The range of clinical manifestations and their severity depend on the type of mutation, its location and the influence of genetic modifiers. Four clinical cases of the neonatal form of Marfan syndrome are presented. Two patients with the same missense mutations and different clinical presentations, a milder patient with a splice site mutation leading to protein shortening, and a girl with severe skeletal damage with deletion of exons 25–29. The purpose of this publication is to analyze the genotype-phenotype correlation of neonatal Marfan syndrome patients with mutations in exons 24–32 of the FBN1 gene.

The impact of the new coronavirus infection (SARS-CoV-2) on the state of the cardiovascular system in minor athletes is uncertain. The “golden” standard for their detection is cardiac magnetic resonance imaging with gadolinium contrast. However, mass screening of athletes using magnetic resonance imaging has not shown any advantage over conducting research according to indications. An analysis of the results of an in-depth medical examination of 1505 young athletes, members of youth teams of the Russian Federation, who were examined at the Center for Syncope and Cardiac Arrhythmias from September 1, 2021 to June 31, 2022, was carried out. 236 athletes (15.7%) suffered SARS-CoV-2 infection for the 6 months preceding the in-depth medical examination. Stage I of the examination included examination, electrocardiography, echocardiography, and bicycle ergometry. 22 athletes (9.3%) required a more in-depth examination due to the identified changes in the first stage (stage II). It included Holter monitoring with assessment of heart rate turbulence, microvolt alternation of the T wave and heart rate variability, and high-resolution electrocardiography. Seven athletes (32%), with changes identified at this stage, were sent for magnetic resonance imaging (stage III). Based on its results, myopericarditis was diagnosed in 4 cases (1.7% of 236), and the necessary treatment and observation were prescribed. Conclusion. There is a low (less than 2%) involvement of myocardial damage in young elite athletes who have had SARS-CoV-2 infection. Additional methods of non-invasive electrocardiology, such as high-resolution electrocardiography, Holter monitoring with assessment of heart rate variability, heart rate turbulence and microvolt alternation of the T wave, make it possible to determine indications for cardiac magnetic resonance imaging.

Thrombophilias are hereditary and acquired conditions characterized by an excessive tendency of the body to form thrombi in the blood vessels. Idiopathic venous thrombosis can often occur in childhood and can also be associated with certain genetic variants of hereditary predisposition to thrombophilia.

Purpose. To analyze the association of 8 genetic variants (F2 20210G>A, F5 1691G>A, F7 10976G>A, F13 G>T, ITGA2 807C>T, ITGB3 1565 T>C, PAI-1–675 5G>4G) with venous thrombosis in children born to mothers with a burdened obstetric and gynecological history.

Material and methods. The patient group included 322 children aged 7 to 14 years (average age 9.3 years), who had a history of episodes of venous thrombosis of various locations, born to mothers with obstetric and gynecological history. The comparison group included 159 healthy children also aged from 7 to 14 years (average age 9.5 years), who did not have a history of episodes of venous thrombosis and who were also born to mothers with obstetric and gynecological history. Molecular genetic analysis was carried out using real-time PCR with automatic analysis of melting curves.

Results. Based on the results of an analysis of the association of genetic variants with venous thrombosis in children born to mothers with obstetric and gynecological history, a connection with this pathology was established for genetic variants F5 1691G>A (genotype GA+AA, OR=3.33, 95% CI: 1.19 — 9.36), ITGA2 807C >T (TT genotype (OR=1.92, 95% CI:1.20 — 3.06) and heterozygous CT (OR=1.46, 95% CI: 1.10 — 1.93)) and ITGB3 1565 T>C (CC genotype (OR=2.77 95% CI:1.08 — 7.02) and TC (OR=1.40, 95% CI: 1.07 — 1.83)).

Conclusion. Thus, we established an association of 3 genetic variants (Leiden mutation, ITGA2 807C>T and ITGB3 1565 T>C) with venous thrombosis in children born to mothers with obstetric and gynecological history.

Prader-Willi syndrome (PWS) (OMIM #176270) is a neurobehavioral disorder that is caused by various genetic mechanisms. These mechanisms include a deletion in the q11.2–q13 region of the paternal chromosome 15, maternal uniparental disomy of chromosome 15, or a pathology of gene imprinting in the proximal part of the long arm of chromosome 15. The most common cause of PWS is a 15q11.2–q13 deletion of approximately 6 Mb, which typically occurs spontaneously. However, there have been rare cases of 15q11.2–q13 deletion associated with unbalanced translocations involving chromosome 15. In order to accurately diagnose PWS and determine the mechanisms behind the chromosomal imbalance, various diagnostic methods such as conventional cytogenetics, fluorescence in situ hybridization (FISH) or microarray comparative genomic hybridization are necessary.

The aim. To determine the origin of an atypical 15q deletion in a patient with Prader–Willi syndrome.

Methods. Conventional cytogenetic study, FISH with DNA probes for chromosomes 13 and 15, and chromosomal microarray analysis.

Results. Showed that the patient had an 8.7 Mb deletion in the 15q11.2–q13.3 region, which was found to be a consequence of a meiotic malsegregation of a reciprocal translocation between chromosomes 13 and 15 in the patient’s father. The scope of the results is in informing medical genetic counseling of patients and families with a hereditary disease.

Conclusion. A comprehensive cytogenomic approach in diagnosis of genetic variations associated with Prader–Willi syndrome allows for accurate determination of copy number variations and provides information on the structure and origin of genomic imbalance. This information can be valuable for guiding medical genetic counseling and making decisions regarding future prenatal or preimplantation diagnoses.

Purpose. To analyze the incidence, structure and methods of treatment of active retinopathy of prematurity (ROP) in a modern hightech perinatal center by specialists from the federal ophthalmology clinic.

Material and methods. The results of ophthalmological monitoring of 979 premature babies were analyzed. The children’s body weight at birth were 460–2200 g. The gestational age of the children was 22–36 weeks. The children were nursed in the perinatal center “Kaluga Regional Clinical Hospital” from 2021 to 2023. Indications for the treatment were the identification of the 2nd and 3rd stages of active ROP with an unfavorable course, aggressive posterior ROP and ROP of the 1st zone.

Results. For the analyzed period, active ROP was registered in 125 children (12.77%), the aggressive posterior ROP was registered in 4 (0.4%) cases. In the structure of morbidity, ROP with a favorable course accounted for 72% of cases (90 children). The proportion of the 2nd and 3rd stages of ROP with an unfavorable course, subject to treatment was 2.4% and 22.4%, respectively, and aggressive posterior ROP was 3.2%. Treatment of active ROP with an unfavorable course was required in 28% of cases. In 2021, among the used treatment methods, the leading place belonged to laser coagulation of the retina — 72.2%. The technique of intravitreal injections of an angiogenesis inhibitor was used in 2022 in 46.2% of cases, and in 2023 it reached 100%. By 2023, the effectiveness of the treatment with achieving regression of ROP was 100% of cases.

Conclusion. Modern high-tech capabilities for providing care to premature infants in Perinatal Centers, combined with the use of advanced technologies from specialized ophthalmological centers, allow for timely high-tech treatment of active ROP, which ensures that the incidence of severe, disabling forms of the disease is minimized.

Juvenile psoriatic arthritis is a chronic inflammatory disease of the peripheral joints, spinal joints and entheses, which occurs in 10–25% of patients with psoriasis. Studying the features of the juvenile psoriatic arthritis debut will increase early diagnosis and will help to avoid disability, socialize and integrate the child into society.

Purpose. To identify the relationship between the onset of juvenile psoriatic arthritis and the age and gender of the child, to trace the nature of the articular syndrome in our patients from the onset to the height of the disease.

Methods. 155 patients with an established diagnosis of juvenile psoriatic arthritis were examined. To analyze the data, universal nonparametric (randomization-permutation) algorithms for constructing confidence intervals (CI) and statistical comparisons based on the bootstrap and Monte Carlo methods were used.

Results. It was possible to identify a relationship between the onset variant and the gender of the child. The incidence of asymmetric oligoarthritis in boys and girls at onset was approximately the same, 68% and 59%, respectively, and did not differ significantly. At onset, girls had a higher incidence of rheumatoid-like arthritis (37%) (p<0.005), and boys had a higher incidence of spondyloarthritis (26%) (p<0.005). A relationship was also revealed between the onset, gender and age of the child. Girls aged 0–6 years most often debuted with asymmetric oligoarthritis (90%) (p<0.005), and at the age of 11–15 years — with the rheumatoid-like (polyarticular) variant (73%) (p<0.005). In boys aged 0–6 and 7–10 years, asymmetric oligoarthritis predominated (100% and 100%, respectively) (p <0.005), and at the age of 11–15 years, spondyloarthritis with damage to peripheral joints was more common (73%) (p<0.005). A transformation of the articular syndrome was revealed: if at the onset of the disease asymmetric oligoarthritis was most common (63%), then 5 years from the onset of the disease, 40.7% of the observed children had a rheumatoid-like (polyarticular) variant of the disease.

Conclusion. The course of juvenile psoriatic arthritis may be influenced by the gender and age of the child at onset; a certain pattern of the course of juvenile psoriatic arthritis from oligoarthritis to the polyarticular (rheumatoid-like) variant has been identified.

The prevalence of smoking, use of tobacco and nicotine-containing products among children and adolescents is a significant problem of our time. The continuing high prevalence of child and adolescent smoking and contradictory statistical data for certain regions of the Russian Federation determine the need to study this topic.

Purpose. To study the prevalence and risk factors of smoking among children and adolescents in the Republic of Bashkortostan.

 Material and methods. A one-stage continuous study oftobacco smoking among children aged 7 to 17 years was conducted using an anonymous voluntary online questionnaire of schoolchildren using the Google questionnaire form. 76 543 respondents took part in the study.

Results. The study showed that 2.5% of children and adolescents are smokers. More than 3/4 of them smoke daily, most of them prefer electronic cigarettes. Every fourth child is not motivated to quit smoking. Half of smoking children first try smoking at the age of 12–17 years, 1/3 — at the age of 10 years. The reasons for introducing children to smoking are the example of parents, friends and classmates, the availability of smoking products. Every third child who smokes feels a deterioration in their health. Every second child is open to communication with adults and is ready to listen to medical conversations.

Conclusion. To reduce the prevalence of smoking among children and adolescents, competent, scientifically based multidisciplinary work is needed with the introduction of regional multicomponent prevention programs.

X-linked filaminopathies are a diverse group of orphan diseases caused by mutations in the FLNA gene which encodes the cytoskeletal actin-binding protein filamin A. Pathogenic variants in this gene cause a wide range of genetic syndromes with signs of organ and tissue damage — skeletal dysplasia, cardiovascular and renal abnormalities. One of a group X-linked filaminopathies is frontometaphyseal dysplasia 1 (OMIM 305620). A clinical case of a 15-year-old boy with congenital anomalies of the kidney and urinary tract: posterior urethral valves, bilateral megaureter, neurogenic bladder was presented. In addition, the patient had congenital heart disease: atrial septal defect, valvular pulmonary artery stenosis and secondary chronic cicatricial-granular stenosis of the larynx. Phenotypic deviations were manifested by skeletal abnormalities that included facial dysmorphism — prominent brow ridges, wide bridge of the nose, orbital hypertelorism, small pointed chin; high-degree scoliosis; valgus deformity of the lower extremities; contractures of various joints. The child was short stature and had multiple congenital developmental features. New-generation whole-exome sequencing (Illumina, NextSeq 550) made it possible to detect a non-synonymous hemizygous variant of the FLNA gene: c.3557G>A (p.S1186L, rs137853312). The identified mutation was confirmed by Sanger sequencing. Genetic testing of the parents was carried out and the c.3557G>A hemizygous mutation was found in the patient’s mother. The use of NGS makes it possible to identify rare hereditary syndromes and make an accurate diagnosis, which is very important for choosing the right management of patient. 

Mucolipidosis type IV is a rare autosomal recessive disease from the group of lysosomal accumulation diseases caused by a malfunction of the cation channel due to mutations in the MCOLN1 gene. The clinical symptom complex includes a combination of neurological symptoms (impaired speech and motor development, spasticity, rigidity), corneal opacity and achlorhydria with iron deficiency anemia. The literature data on this disease and the medical history of a 13-year-old girl who was observed in the Department of Clinical Genetics of the Veltischev Institute are presented. The child had a characteristic clinical picture, including damage to the nervous system: decreased intelligence, muscular dystonia and spasticity, salivation, strabismus, hypoplasia of the corpus callosum; damage to the organ of vision — corneal opacity, cataracts, myopia, photophobia in combination with persistent iron deficiency anemia (apparently due to achlorhydria). The diagnosis was confirmed by the results of DNA diagnostics — a known pathogenic mutation NM_02533.3 was detected in the MCOLN1 gene: c.304C>T (p.Arg102Term) in a homozygous state; in the girl’s mother — in a heterozygous state. A differential diagnosis was made with phenotypically similar diseases, primarily with cerebral palsy, mucopolysaccharidosis, and other types of mucolipidosis. Further medical supervision of the child should be carried out with the obligatory participation of a neurologist, an optometrist, a gastroenterologist, an orthopedist and a nephrologist. Knowledge of the clinical features of pathology ensures more successful medical care with the prevention of complications. 

Chronic mucocutaneous candidiasis is a complication occurring in patients with congenital immune disorders, characterized by recurrent infections of the skin, nails, and mucous membranes caused by C. albicans. The STAT1 gain of function (GOF) defect is a primary immunodeficiency condition resulting from heterozygous gain of function mutations in the STAT1 gene. STAT1 is a regulatory transcription factor and a key component of the JAK-STAT pathway mediating interferon-α/β/γ signaling. GOF mutations in the STAT1 gene lead to hyperphosphorylation of the protein of the same name and increased signaling along the JAK-STAT pathway, which also leads to impaired development of type 17 T helper cells (Th17). This disease most often debuts in childhood, and clinically, it is characterized by chronic mucocutaneous candidiasis, multiorgan autoimmune complications and an increased risk of infectious complications. The article describes the clinical observation of a girl with a rare variant of primary immunodeficiency STAT1 GOF.