Introduction. Oxidative phosphorylation deficiency, type 10 is a rare variant of mitochondrial disease characterized by lactate acidosis, damage to the cardiovascular and central nervous systems. Given the variability of phenotype-genotypic correlations, a detailed description of the clinical picture of the disease is important for understanding possible variants of the course of the disease.Materials and methods. During a molecular genetic study of three hundred fourteen pediatric patients with a guiding diagnosis of hypertrophic cardiomyopathy, one patient with a deficiency of oxidative phosphorylation, type 10, was identified.Results. The analysis of the nature of the disease course during the period of dynamic follow-up (over 3 years) was carried out.Conclusion. Deficiency of oxidative phosphorylation, type 10, is a rare cause of the hypertrophic phenotype of cardiomyopathy. Isolated cases of this disease have been described in the literature, which makes the observation significant for a wide range of specialists (pediatricians, neurologists, cardiologists).Compliance with ethical standards. Voluntary informed consent was obtained from the patient’s legal representative for the publication of material related to the patient in Russian and foreign medical periodicals (dated October 1, 2024). Contribution:Shifova N.A. — concept and design of research, collection and processing of material, writing, editing;Gandaeva L.A. — editing;Globa O.V. — editing;Silnova I.V. — editing;Davydova Yu.I. — editing;Basargina E.Y. — editing;Savostyanov K.V. — the concept and design of the study.All co-authors are responsible for the integrity of all parts of the manuscript and approval of its final version.Funding. The study had no sponsorship.Conflict of interest. The authors declare no conflict of interest.Received: August 18, 2025Accepted:September 30, 2025Published: January 31, 2026

Background. The genetic etiology of hypertrophic cardiomyopathy (HCM) is complex and population-specific, yet Russian HCM patients remain understudied. Methods. Between 2015-2025, unrelated pediatric and adult HCM patients were genotyped in a single laboratory. Children were sequenced with a 404-gene panel and adults with a 17-gene panel. Genotype-phenotype correlations were assessed for carriers of the most frequent variant, MYBPC3 c.3697C>T, and compared with patients harboring other MYPBC3 variants. Haplotype analysis explored its potential founder effect. Results. The cohort comprised 315 children (mean age 11.7 years, 61% male; 127 infant-onset) and 3,409 adults (mean age 47.5 years, 58% male). Genotype-positive rates were 89% in children and 28% in adults. Sarcomeric and RASopathy variants accounted for 35% and 33% of infant-onset, 56% and 17% of childhood-onset, and 22% and 0.4% of adult-onset genotyped cases, respectively. The MYBPC3 c.3697C>T variant was identified in 83 patients (2.2%). Compared with controls (n = 85), carriers (n = 58) more often had left ventricular ejection fraction below 50% (9% vs. 1%, p = 0.038), left atrial dilation (76% vs. 47%, p = 0.001), and supraventricular arrythmias (45% vs. 25%, p = 0.027). Pediatric carriers showed no left ventricular outflow tract obstruction (0% vs. 29%, p = 0.024) and fewer conduction disturbances (13% vs. 48%, p = 0.029). Intervention rates and outcomes were similar across ages. Haplotype analysis was inconclusive for founder effect. Conclusions. The genetic spectrum of HCM in Russian population largely mirrors Western data. Within MYBPC3-associated HCM, the c.3697C>T variant is linked to a milder, nonobstructive pediatric phenotype and increased hypokinetic progression in adults but does not influence overall outcomes. Its high prevalence likely reflects a combination of founder and recurrent mutational events. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee/IRB of National Medical Research Center for Children Health gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors

Barth syndrome (BS) is an orphan disease whose variability of clinical manifestations does not always allow its timely diagnosis, which in its turn reduces the quality of medical care and worsens the prognosis for outcomes. Currently there are some scientific publications in Russia on isolated cases of the disease and none of a kind dedicated to the long-term observation of patients with assessment of the clinical picture. The purpose of this research was to analyze the dynamics of clinical manifestations in children with BS. Materials and methods used: a cohort study included observation of 9 boys with BS in 2015-2022. Results: all patients with genetically confirmed BS were diagnosed with cardiomyopathy with non-compact myocardium, while a dilated remodeling phenotype was noted in 78% of cases. In 67% of children, against the background of complex drug therapy, a decrease in the size of the left ventricle with an increase in ejection fraction was recorded. Neutropenia was detected in 89% of patients, requiring the use of granulocyte colony-stimulating factor in two cases. Frequent detection of prolongation of the QT interval (78%) and ECG patterns simulating the phenomenon of pre-excitation against the background of intraventricular conduction disturbances, acceleration of AV conduction, secondary disturbances of repolarization processes (44%) without fixation of ventricular arrhythmias were noted. The severity of the condition was determined by a combination of severe heart failure, conduction disturbances and clinically significant neutropenia. Fatal outcomes were recorded in 2 children (22%) at the age of 8 months old and 3.5 years old against the background of progressive heart failure and sudden death, respectively. Conclusion: a comprehensive multidisciplinary approach and early diagnosis of BS have an impact on the outcome of the disease.

Introduction. Generalized infantile arterial calcification (IAC) is a rare autosomal recessive disease. The diagnosis of IAC is associated with great difficulties due to the variability of clinical manifestations. The high mortality rate in patients at the onset of the disease in early childhood is characterized due to limited possibilities of drug treatment. Aim: to present two clinical reports concerning patients with a genetically verified diagnosis of IAC with long-term catamnestic follow-up (from 2016 to 2023). Results. When coronary vessels are affected with IAC, pronounced ischemic changes are detected on the ECG with confirmed normal anatomy of the coronary arteries, which should alert clinicians and contribute to the inclusion of this form of pathology in the spectrum of differential diagnoses. Conclusion. For the diagnosis of genetically determined IAC, it is extremely important to conduct molecular genetic studies using high-throughput sequencing methods.

Introduction. Acyl-CoA dehydrogenase 9 deficiency (mitochondrial complex I deficiency) is an autosomal recessive disease from the heterogeneous group of disorders of mitochondrial β-oxidation of fatty acids caused by mutations in the ACAD9 gene. The disease is characterized by a wide range of clinical manifestations, the most common of which are metabolic acidosis, hypertrophic cardiomyopathy, muscle hypotonicity, and impaired motor skills. The article presents the first Russian clinical observation of a rare variant of hypertrophic cardiomyopathy with early debut in a patient with mitochondrial complex I deficiency caused by homozygous mutation c.659C>T (p.A220V) in the ACAD9 gene and emphasizes the importance of early diagnosis of the disease and complex drug therapy to prevent the development of severe complications. Objective: to describe the clinical course and management of a patient with the pathogenic c.659C>T (p.A220V) variant of the ACAD9 gene. Detailed analysis of anamnesis data, results of clinical, laboratory, instrumental diagnostic methods, and molecular genetic research performed using high-throughput sequencing and direct Sanger sequencing technology. The article presents a literature review and detailed data on clinical observation of a child with homozygous c.659C>T (p.A220V) mutation in the ACAD9 gene diagnosed on the basis of the cardiology department of the National Medical Research Center for Children’s Health. Early disease markers and possibilities of complex drug therapy to prevent the development of severe complications are described. Conclusion. Disruption of mitochondrial beta-oxidation of fatty acids is a heterogeneous group of inherited diseases due to abnormal mitochondrial beta-oxidation and transport of carnitine and fatty acids in mitochondria. A feature of these diseases is the multisystem nature of the lesion and its progressive course. In some cases, the initial clinical manifestations may be various disorders of the cardiovascular system (cardiomyopathy, heart rhythm disturbances), which may cause death in neonatal period and early childhood. Early molecular genetic research provides accurate diagnosis and, accordingly, timely prescription of complex therapy.

Objective. To evaluate the results of 72-hour monitoring of Holter electrocardiograms with telemetry in children with hypertrophic cardiomyopathy (HCM). Patients and methods. A randomized retrospective study of 55 children with the confirmed diagnosis of HCM was conducted on the basis of the Federal State Autonomous Institution of the Ministry of Health of Russian Federation "National Children Medical Research Center"; all patients were hospitalized in the cardiology department for the examination and treatment in the period 2021–2023. The study included 33 boys and 22 girls aged 6 to 17.8 years; age and documented functional limitations in both groups were comparable. All patients underwent electrocardiography (ECG) on the 12-channel electrocardiograph; 3-channel 3-day monitoring of Holter electrocardiograms with telemetry using the Astrocard-Telemetry 3G complex (Meditek, Russia); magnetic resonance imaging (MRI) of the heart with intravenous contrast. Parents of 43 patients filled out questionnaires identifying direct and indirect signs of sleep disorders. The obtained data were presented in fractions, as well as as M ± m; minimum, Q1, Q3, maximum; and the Kendall rank correlation coefficient and the Friedman criterion were calculated daily. The differences were considered significant at p < 0.05. The work has been approved by an independent local ethics committee. All parents (or legal representatives) of the children signed the voluntary informed Results. 12-channel ECG revealed various and non-specific disorders (arrhythmias, signs of overload of the heart chambers) in 50 (90.9%) patients. Long-term (3-day) Holter monitoring revealed practically no significant differences in the mean values of the studied indicators between days; by the 3rd day of the study, two trends were revealed: an increase in the average number of episodes of ventricular tachycardia (p = 0.058) and an elongation of the QTc interval in boys (p = 0.053). The significant decrease in heart rate was recorded in girls on the 3rd day of the study (p = 0.011). According to the results of MRI, intramyocardial fibrosis was detected in 37 (67.3%) cases: in 23 (69.7%) boys and 14 (63.6%) girls. In 16 (29.1%) patients, the volume of myocardial lesion was ≥10%. Direct and/or indirect signs of respiratory disorders during sleep were recorded in 28 (65.1%) children. In children with signs of sleep disorders, significant positive correlations were found with the number of supraventricular and ventricular extrasystoles and episodes of ventricular tachycardia. Signs of an increased risk of sudden vascular death were recorded in 8 (14.5%) children. Conclusion. Long-term (3-day) Holter monitoring of electrocardiograms is well adapted to children; all major rhythm disturbances were detected during the first 24 hours. Prolongation of the study may be recommended to solve certain clinical problems (diagnosis of syncopal conditions, paroxysms of unclear etiology, sleep apnea). In children with HCM, it is necessary to identify direct and indirect signs of sleep disorders that have significant correlations with cardiac arrhythmias, including those that are an integrative indicator of the risk of sudden cardiac death. Key words: sudden cardiac death, hypertrophic cardiomyopathy, children, multi-day monitoring of electrocardiogram with telemetry, rhythm disturbances, sleep disorders

Introduction. Noonan syndrome is a clinically and genetically heterogeneous disease with multiple organ involvement associated with mutations in the genes of the RAS/MAPK signalling pathway. Most patients with Noonan syndrom (up to 50–80%) have disorders of the cardiovascular system, presented by a wide range of congenital heart defects and/or cardiomyopathy, predominantly hypertrophic phenotype. Thanks to the introduction of high-throughput sequencing, knowledge of the genetic causes of Noonan syndrome has expanded significantly, so since 2014, the LZTR1 gene (OMIM 601247) has been included in the list of genes responsible for the development of Noonan syndrome. The nucleotide variants of this gene are known to be inherited both in an autosomal dominant and autosomal recessive manner. However, the number of reports describing the clinical and genetic characteristics of patients with LZTR1 gene mutations is scarce in the world scientific literature. Objective. To describe the clinical features of Noonan syndrome with an autosomal recessive type of inheritance caused by biallelic variants c.1259A>G (p.Q420R) and c.2051T>C (p.I684T) in the LZTR1 gene. Materials and methods. A detailed analysis of the history data, the results of clinical, laboratory, and instrumental studies, a molecular genetic study using high-throughput sequencing technology and direct Sanger sequencing was carried out. After verifying the biallelic variants in the proband, a search was made for the identified nucleotide substitutions in the venous blood samples of the parents and sibs. Results. The article presents the data of a clinical observation of a rare case of Noonan syndrome caused by pathogenic variants in the LZTR1 gene with an autosomal recessive type of inheritance by the Department of Cardiology of the National Medical Research Center for Children’s Health of the Ministry of Health of Russia. Conclusion. The diversity of clinical manifestations makes it difficult to diagnose Noonan syndrome based on phenotype alone. The possibility of using high-throughput sequencing improves the quality of diagnostics, contributes to the replenishment of data on new pathogenic variants and the establishment of genotype-phenotypic correlations.

Introduction. In 2006, the American Heart Association identified two main groups of cardiomyopathies (CM) as primary and secondary, referring to the primary CM heart diseases of genetic, acquired or mixed etiology, and to the secondary — pathological involvement of the myocardium as a part of a systemic pathology. Aim: to determine the most common phenocopies of hypertrophic CM (HCM) in children, due to the accumulation of pathological substances in the myocardium and present their differences. Materials and methods. Instrumental diagnostic methods (echocardiography, electrocardiography, 24-hour Holter ECG monitoring), laboratory tests (N-terminal propeptide of natriuretic hormone, creatine phosphokinase, creatine phosphokinase-MB, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, lactate, ammonia), and molecular genetic tests were used. Results. Nucleotide variants in non-sarcomeric genes causing myocardial hypertrophy were identified in one hundred four (39%) patients: infiltrative diseases with heart damage were diagnosed in 46 cases, syndromes from the RAS-pathy group were diagnosed in 58 cases. Patients with storage diseases included 12 children with Pompe disease, 2 cases with PRKAG2 syndrome, 11 cases had Danon disease, 15 — Corey–Forbes disease, and 6 — Friedreich ataxia. Adverse events were reported in group of patients with Pompe disease (9 deaths), and with Danon’s disease (2 deaths). Conclusion. The phenocopy varieties of HCM in children are represented by a wide variety of genetic variants and often by diseases from the group of glycogen metabolism disorders, fatty acid oxidation disorders, and mitochondrial diseases. Identification of the genetic causes of ventricular myocardial hypertrophy in children is the key to early diagnosis of rare diseases, timely and adequate treatment, as well as predicting the course and outcome of the disease.

Introduction. Noonan syndrome is a clinically and genetically heterogeneous disease with multiple organ involvement associated with mutations in the genes of the RAS/MAPK signalling pathway. Most patients with Noonan syndrom (up to 50–80%) have disorders of the cardiovascular system, presented by a wide range of congenital heart defects and/or cardiomyopathy, predominantly hypertrophic phenotype. Thanks to the introduction of high-throughput sequencing, knowledge of the genetic causes of Noonan syndrome has expanded significantly, so since 2014, the LZTR1 gene (OMIM 601247) has been included in the list of genes responsible for the development of Noonan syndrome. The nucleotide variants of this gene are known to be inherited both in an autosomal dominant and autosomal recessive manner. However, the number of reports describing the clinical and genetic characteristics of patients with LZTR1 gene mutations is scarce in the world scientific literature. Objective. To describe the clinical features of Noonan syndrome with an autosomal recessive type of inheritance caused by biallelic variants c.1259A>G (p.Q420R) and c.2051T>C (p.I684T) in the LZTR1 gene. Materials and methods. A detailed analysis of the history data, the results of clinical, laboratory, and instrumental studies, a molecular genetic study using high-throughput sequencing technology and direct Sanger sequencing was carried out. After verifying the biallelic variants in the proband, a search was made for the identified nucleotide substitutions in the venous blood samples of the parents and sibs. Results. The article presents the data of a clinical observation of a rare case of Noonan syndrome caused by pathogenic variants in the LZTR1 gene with an autosomal recessive type of inheritance by the Department of Cardiology of the National Medical Research Center for Children’s Health of the Ministry of Health of Russia. Conclusion. The diversity of clinical manifestations makes it difficult to diagnose Noonan syndrome based on phenotype alone. The possibility of using high-throughput sequencing improves the quality of diagnostics, contributes to the replenishment of data on new pathogenic variants and the establishment of genotype-phenotypic correlations.

Successful therapy in a cohort with early onset Danon disease (DD) highlights the potential importance of earlier disease recognition. We present experience from the largest National Pediatric Center in Russia for cardiomyopathy patients. This report focuses on identification of early clinical features of DD in the pediatric population by detailed pedigree analysis and review of medical records. RESULTS: Nine patients (3 females) were identified with DD at the Russian National Medical Research Center of Children's Health ("National Pediatric Center") aged birth to 16 years. At presentation/evaluation: all patients had left ventricular hypertrophy (LVH), ECG features of Wolff-Parkinson-White (WPW), and an increase in hepatic enzymes (particularly lactate dehydrogenase (LDH)); three had marked increase in NT-proBNP; two had HCM with impaired LV function; one had LVH with LV noncompaction; five had arrhythmia with paroxysmal supraventricular and/or ventricular tachycardia. Two teenagers died at ages 16-17 from refractory heart failure and two underwent heart transplantation. All patients were found to have a pathogenic/likely pathogenic variant in the LAMP2 gene, six patients had no family history and a de novo evolvement was documented in 4/6 of those available for genetic tested. Retrospective review related to family background and earlier clinical evaluations revealed a definitive or highly suspicious family history of DD in 3, early clinical presentation with cardiac abnormalities (ECG, echo) in 3, and cerebral, hepatic and/or neuromuscular symptoms in 5. Abnormalities were detected 9,5 months to 5,8 years, median 3,5 years prior to referral to the National Pediatric Center. CONCLUSION: The earliest clinical manifestations of Danon disease occur in the first 12 years of life with symptoms of skeletal muscle and cerebral disease, raised hepatic enzymes, and evidence of cardiac disease on ECG/echo.

The few foreign papers of the last decade have shown the relationship of various pathogenic variants of the ELAC2 gene to heterogeneous phenotypic manifestations, for which the unfavorable prognosis is common, caused by severe cardiomyopathy in the first year of life. The article presents the first clinical observation of a rare variant of the hypertrophic phenotype cardiomyopathy with a fatal outcome in the first year of life, and variants c.887T>C, p.L296P and c.1979A>T, p.K660I of the ELAC2 gene in Russia. The purpose of the work is to present clinical observation of a child with an early manifestation of a hypertrophic phenotype of cardiomyopathy caused by pathogenic variants of the ELAC2 gene.

PRKAG2 syndrome is a rare genetic disease that isinherited in an autosomal dominant fashion and is caused by mutationsin the PRKAG2 gene. Clinical symptoms include early onset, ventricular preexcitation, cardiac hypertrophy, and progressive atrioventricular block. The PRKAG2 syndrome is characterized by genetic heterogeneity, which makes early detection difficult; genophenotypic correlations have been documented. In this article, we provide an overview of the literature data and experience from the cardiology department of the National Medical Research Center for Children’s Health of the Russian Ministry of Health in the diagnosis and management of patients with PRKAG2 syndrome, and present the clinical and genetic characteristics of the p.R302Q and p.H383R variants of the PRKAG2 gene.

Гандаева Л.А., Каверина В.Г., Басаргина Е.Н., Пушков А.А., Савостьянов К.В. Гипертрофическая кардиомиопатия в структуре RAS-патий у детей. Детские болезни сердца и сосудов. 2022; 19 (4): 297–303. DOI: 10.24022/1810-0686-2022-19-4-297-303 HTML

About 80-90% of patients with Noonan syndrome have changes in the cardiovascular system, 30% of which include cardiomyopathy, hypertrophic phenotype in particular. The treatment of cardiomyopathy patients with Noonan syndrome is carried out according to the clinical recommendations for the treatment of chronic heart failure (CHF) and cardiomyopathy. Surgical treatment of progressive nature of heart failure with left ventricular outflow tract obstruction and mitral regurgitation can be one of the possible methods. The review presents our experience with septal myectomy (SM) in children suffered from hypertrophic obstructive cardiomyopathy with Noonan syndrome. Objective. To assess the efficiency of septal myectomy in children suffered from hypertrophic obstructive cardiomyopathy with Noonan syndrome. Materials and methods. Clinical examination (family history, patient examination), lab tests (NT-proBNP level), echocardiography, electrocardiography, Holter monitoring, Chest X-rays and molecular genetic methods using mass parallel sequencing (NGS) and direct automatic Sanger sequencing. The indications for the SM were determined according to the clinical guidelines for the diagnostic and treatment of hypertrophic cardiomyopathy. Results. 7 patients out of 48 with Noonan syndrome underwent SM and 1 with Noonan syndrome with multiple lentigo (LEOPARD). Two of them required the removal of obstruction of the outflow tracts of both ventricles, followed by plastic removal of the right ventricle and pulmonary artery valve. Related surgical interventions included aortic (n = 1) and mitral valves (n = 2), permanent pacemaker (n = 1) in the early postoperative period. After a year, all children recorded a decline of NT-proBNP from the average of 16,198 to 3,865 pg/ml, a significant improvement in health, disappearance of shortness of breath, increased physical activity tolerance, improved physical (weight, growth) and speech development. When assessing the dynamics of the Echo parameters 1 year after the SM, normalization of the size of both atria in 4 cases, reduction of severity of isolated dilation of the left atrium in 2 cases was noted. No cases of repeated obstruction have been reported. Conclusion. Hypertrophic cardiomyopathy (HCM) can be in structure of hereditary syndromes such as Noonan syndrome. Septal myectomy (SM) can now be used in the case of progressive nature of heart failure with left ventricular outflow tract obstruction in children with Noonan syndrome.

Left ventricular non-compaction cardiomyopathy (LVNC) is a rare heart disease, with or without left ventricular dysfunction, which is characterized by a two-layer structure of the myocardium and an increased number of trabeculae. The study of familial forms of LVNC is helpful for risk prediction and genetic counseling of relatives. Here, we present a family consisting of three members with LVNC. Using a next-generation sequencing approach a combination of two (likely) pathogenic nonsense mutations DSG2-p.S363X and TBX20-p.D278X was identified in all three patients. TBX20 encodes the cardiac T-box transcription factor 20. DSG2 encodes desmoglein–2, which is part of the cardiac desmosomes and belongs to the cadherin family. Since the identified nonsense variant (DSG2-p.S363X) is localized in the extracellular domain of DSG2, we performed in vitro cell transfection experiments. These experiments revealed the absence of truncated DSG2 at the plasma membrane, supporting the pathogenic relevance of DSG2-p.S363X. In conclusion, we suggest that in the future, these findings might be helpful for genetic screening and counseling of patients with LVNC.

Introduction. Pompe disease (PD) or type II glycogenosis is a rare multisystem hereditary accumulation disease caused by a deficiency of the enzyme acid maltase (acid alpha-1,4-glucosidase), which leads to reduced activity to the accumulation of glycogen in various organs and tissues of the body. The aim of the study is to develop a high-performance method of early biochemical diagnosis of PD and optimization of its molecular genetic diagnosis. Materials and methods. The characteristics of the relative frequencies and spectrum of the detected mutations were studied using a sample of 7670 patients with suspected Pompe disease admitted to the National Medical Research Center of Children’s Health of the Ministry of Health of Russia as part of the selective screening, as well as eight patients with PD, whose laboratory diagnosis was made outside the framework of this selective screening. Results. As a result of selective screening of PD in Russian patients from high-risk groups, the detectability was 0.47%. PD’s clinical and age characteristics in both children and adults are described. The relative frequencies are calculated, and the spectrum of 47 pathogenic variants of the GAA gene responsible for the occurrence and development of Pompe disease in 44 patients is characterized. Seventeen new mutations of the GAA gene, unknown previously, have been identified and described, adding 2.7% to the HGMD database. Conclusion. Optimization of the algorithm of molecular diagnosis of Pompe disease in Russian patients is proposed.

Aim. To identify the proportion of restrictive cardiomyopathy (RCM), as well as cardiomyopathy (CMP) with a restrictive type of hemodynamics among all cases of genetic CMP and to determine the relative frequencies and spectrum of nucleotide variants in Russian children with RCM, as well as to search for phenogenotypic correlations.Material and methods. The study included 689 children with CMPs. All children underwent a molecular genetic testing of the target regions of 419 genes responsible for various cardiomyopathies and channelopathies using the method of massively parallel sequencing (MPS).Results. In 668 (97,0%) children, pathogenic, likely pathogenic nucleotide variants, as well as nucleotide variants with unknown clinical significance, were identified. Of these, 45 (6,7%) patients were selected to determine the molecular genetic characteristics of RCM, 20 of whom had clinical symptoms and morphofunctional structure of RCMP (3,0%), while the remaining 25 (3,7%) children were diagnosed with another CMP type with a restrictive type of hemodynamics. In total, these patients had 41 nucleotide variants in 15 different genes, while 19 (46,3%) variants were pathogenic, 12 (29,3%) — likely pathogenic, 10 (24,4%) — uncertain clinical significance. Pathogenic and likely pathogenic variants were identified in a total of 38 (84,4%) patients, while in 19 (42,2%) patients, the pathogenic variants described earlier were found. The most common genetic marker of RCM in Russian children was TNNI3 gene mutations. In total, they were identified in 12 (25%) children: with RCP — 8 (40%) patients; with CMP with a restrictive type of hemodynamics — 4 (16%) patients. At the same time, the most common mutation of the TNNI3 gene was the nucleotide variant c.575G>A, leading to the amino acid variant p.R192H, described earlier in patients with RCM and identified by us in three (15%) unrelated children with RCM. In addition, a significant difference was found between the averaged values of N-terminal pro-brain natriuretic peptide in patients with mutations in the MYH7 and TNNI3 genes (0,0039, p<0,05), as well as between the peak flow gradient values in children with mutations in TNNI3 and FLNC genes (0,0016, p<0,05), TNNI3 and MYH7 genes (0,039, p<0,05).Conclusion. The results of this study indicate a significant genetic heterogeneity of RCM in Russian children and the need for further research aimed at finding genotype-phenotype associations in order to predict the course of the disease and select the proper therapy.

The article presents the examination of three generations of a family with diagnosed left ventricular noncompaction (LVNC) and various phenotypic manifestations of the disease (isolated, hypertrophic and dilated type of LVNC). As a result of a molecular genetics tests, a previously undescribed single nucleotide deletion in the PRDM16 gene was revealed in all family members with the LVNC phenotype, leading to a frameshift mutation in exon 9 and the formation of a premature termination codon. This gene encodes a transcription factor responsible for after-birth suppressing the expression of genes involved in prenatal and postnatal development. Despite the presence of previous studies showing the relationship of the PRDM16 gene with LVNC development, currently there are insufficient data to prove the pathogenicity of the identified variant. However, the segregation of the symptomatic variant in three generations supports the association of the identified variant with LVNC. With the accumulation of information about changes in PRDM16 in patients with cardiomyopathies, it is possible to change the status of this gene and clarify its contribution to primary heart diseases.

AIM:To analyze and demonstrate various phenotypes in patients with familial left ventricular noncompaction (LVNC).MATERIALS AND METHODS:In 2013 was created a multicenter registry of LVNC patients. On its basis 30 families with a familial LVNC were selected.RESULTS:30 LVNC families were selected from the register. From a total of 115 people (probands and relatives) in 71 (61.7%) LVNC was diagnosed (30 probands and 41 relatives with non-compact myocardial criteria). The most common type of remodeling in patients was the dilated type (DT) (n=30), the isolated LVNC with preserved ejection fraction (EF) was slightly less common (n=23), and the hypertrophic type (GT) was detected in 8 patients. 4 patients were diagnosed with the isolated LVNC with a reduced EF. 3 patients were with a combination of non-compact myocardium with congenital heart disease and with a combination of DT and GT (DT+GT). During the analysis of cases a combination of different phenotypes in the same family was observed. The largest number of families was diagnosed with a combination of DT and the isolated LVNC with preserved EF. The development of cardiovascular complications was associated with DT.CONCLUSION:Family cases of LVNC had different types of myocardial remodeling and variants of clinical course. In one family a combination of different types of left ventricular remodeling is possible. DT is associated with the most severe clinical manifestations. The clinical picture of the isolated LVNC with preserved EF, is the most favorable, but in rare cases, serious clinical manifestations were observed.