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Purpose: to analyze the structure of hereditary pathology and the results of genetic studies in children in a specialized clinic.Results.1045 children from 79 regions of the Russian Federation were examined and treated in the pediatric department of congenital and hereditary diseases in 2018. There were 25% of patients from Moscow and Moscow region and 75% from other territories. After examination all patients were divided into 2 large cohorts: patients with hereditary diseases diagnosed by clinical and laboratory data (737 children; 70%) and patients with undifferentiated pathological conditions with unclear genesis at the time of discharge from the hospital (308 children; 30%). In the cohort of hereditary diseases there were the most numerous (about 100 children in each) groups of patients with Ehlers–Danlos syndrome, imperfect osteogenesis and rare heterogeneous genetic syndromes. The groups of rickets- like diseases, chromosomal syndromes and Rett syndrome included 50-70 patients. Other groups were smaller. Half of the hospitalized patients required genetic analysis. The highest percentage of molecular genetically / cytogenetically confirmed diagnoses was found in the groups of chromosomal diseases, rare genetic syndromes of lysosomal and mitochondrial diseases, Rett syndrome, and aminoacidopathy. It is worth mentioning that a primary diagnosis was not established during a genetic study in 57 children (18%) children from the general cohort of patients with hereditary diseases, so the researchers used other methods of analysis or bioinformatic revision of the results.Conclusion: The authors found a large variety of genetic diseases in children requiring examination and treatment in a specialized hospital. 1/5 of the examined children require additional genetic testing or repeated bioinformatic interpretation of the data.

Адрес для корреспонденции: Семячкина Алла Николаевна-д.м.н., гл. н.с. отдела клинической генетики Научно-исследовательского клинического института педиатрии им. акад. Ю.Е. Вельтищева Николаева Екатерина Александровна-д.м.н., рук. отдела клинической генетики НИКИ педиатрии им. акад. Ю.Е. Вельтищева, ORCID: 0000-0001-7146-7220 Харабадзе Малвина Нодарьевна-к.м.н., зав. педиатрическим отделением врожденных и наследственных заболеваний НИКИ педиатрии им. акад. Ю.Е. Вельтищева Давыдова Юлия Игоревна-врач педиатрического отделения врожденных и наследственных заболеваний НИКИ педиатрии им. акад. Ю.Е. Вельтищева Боченков Сергей Викторович-врач педиатрического отделения врожденных и наследственных заболеваний НИКИ педиатрии им. акад. Ю.Е. Вельтищева Курамагомедова Рабият Газимагомедовна-врач педиатрического отделения врожденных и наследственных заболеваний НИКИ педиатрии им. акад. Ю.Е. Вельтищева 125412 Москва, ул. Талдомская, д.2 Захарова Екатерина Юрьевна-д.м.н., рук. лаборатории генетики наследственных болезней обмена веществ Медико-генетического научного центра 115478 Москва, ул. Москворечье, д. 1

Background. Defects in pyruvate dehydrogenase complex (PDC), involved in the glycolysis products integration into the cells’ energy metabolism, are one of the reasons of mitochondrial pathology development. The diagnosis of this condition can be pretty complicated also due to the lack of description of such patients with encephalomyopathy associated with PDC deficiency in Russian population.Clinical Case Description. We have performed the analysis of clinical manifestations polymorphism of progressive mitochondrial encephalomyopathy caused by pathogenic variants in nuclear X linked gene, PDHA1 (encodes alpha subunit of pyruvate dehydrogenase), in 8 boys aged from 1 to 8 years. The adverse perinatal period was mentioned in all cases. The major features of symptom complex by the time of hospital examination were psychomotor retardation, ataxy, myopathic manifestations. Dystonic attacks were observed in 2 sibs. All patients had changes on brain magnetic resonance imaging: in basal ganglia in 6 children and ventriculomegaly in 2 children. All children had lactic acidosis. Clinical examination has shown that 4 patients had severe damage of nervous system, other 4 patients had moderate damage. Missense mutations in the PDHA1 gene were revealed in 6 children, insertions and duplications including 6 and 16 base pairs — in 2 children. The moderate positive dynamics was noticed as a result of complex treatment of children: stabilization of the overall condition, no metabolic crises, decrease in frequency of dystonic attacks.Conclusion. The clinical polymorphism of mitochondrial encephalomyopathy associated with PDC deficiency is described. The differences in manifestations of severe and moderate forms of disease are shown. The presented description may be useful for medico-genetic counseling and providing medicogenetic care for families.

Angelman syndrome is a genetic disorder characterized by mental retardation and severe speech delay, movement disorders and ataxia, dysmorphic features, and behavioral disorders. Angelman syndrome is caused by the loss of the 15q11.2-q13 region of chromosome 15 received from the mother, which leads to a violation of the expression of the UBE3A gene.Purpose. To analyze clinical manifestations in children with Angelman syndrome to identify early-onset and characteristic clinical signs.Characteristics of children and research methods. The study included 60 children. In all cases, Angelman syndrome was diagnosed on the basis of international clinical criteria and the results of genetic testing. The researchers used clinical, functional and molecular genetic research methods.Results. 80-100% of children demonstrated delayed mental and motor development, lack of speech, affective behavior, ataxia, hand stereotypes, apraxia of hand movements, strabismus, sialorrhea. 72% of children had epileptic seizures; all patients (regardless of the presence / absence of epilepsy) had a pattern characteristic of Angelman syndrome on the electroencephalogram. Differential diagnosis was based on the gene / chromosomal syndromes characterized by similar clinical signs.Conclusion. The combination of such most frequent, early clinical symptoms as difficulties in feeding, strabismus, impaired muscle tone, delayed motor and psycho-speech development, affective behavior with frequent laughter, and sleep disorders may indicate Angelman syndrome in a child.