Members of the working group:

Svetlana B. Artemyeva, MD, PhD, Head of the Neurological department of the Research Clinical Institute of Pediatrics named after Yu.E. Veltishchev; Russian Federation;
Elena D. Belousova, MD, PhD, DSci, Professor, Head of the Department of psychoneurology and epileptology of pediatrics, Research Clinical Institute of Pediatrics named after Yu.E. Veltishchev, Russian Federation;
Dmitry V. Vlodavets, MD, PhD, President of the Association of Pediatric Neurologists in the field of myology NeoMyo, Head of the Russian Children’s Neuromuscular Center at the Research Clinical Institute of Pediatrics and Pediatric Surgery named after Yu. E. Veltishchev; leading researcher, Department of psychoneurology and epileptology, Research Clinical Institute of Pediatrics and Pediatric Surgery named after Yu.E. Veltishchev; Associate Professor of the Department of neurology, neurosurgery and medical genetics named after L.O. Badalyan, Faculty of pediatrics, Russian National Research Medical University named after N.I. Pirogov, Russian Federation;
Sergey V. Voronin, MD, PhD, chief physician of the Medical Genetic Research Center named after N.P. Bochkov, сhief freelance specialist in medical genetics of the Ministry of Health of Russia in the Far Eastern Federal District, Russian Federation; 
Andrey S. Glotov, MD, PhD, DSci., Head of the Department of genomic medicine named after V.S. Baranov of the Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott, Russian Federation;
Valentina I. Guzeva, MD, PhD, DSci., Prof., chief freelance children’s specialist of the Russian Ministry of Health in Neurology, Honored Scientist of the Russian Federation, Head of the Department of neurology, neurosurgery and medical genetics, St. Petersburg State Pediatric Medical University, member of the Presidium of the Russian Society of Neurologists, Russian Federation;
Altynshash K. Jaxybayeva, MD, PhD, DSci., Head of the Department of neurology, Astana Medical University, chief freelance pediatric neurologist of the Ministry of Health of the Republic of Kazakhstan, Republic of Kazakhstan;
Irina V, Zhevneronok, MD, PhD, Associate Professor of the Department of pediatric neurology of the Belarusian Medical Academy of Postgraduate Education, chief specialist of the Ministry of Health of the Republic of Belarus on hereditary neuromuscular diseases in children; Head of the Department of hereditary neuromuscular diseases of the Republican Scientific and Practical Center “Mother and Child”, Republic of Belarus; 
Viktoria S. Kakaulina, neurologist, Center for Orphan and Other Rare Diseases, Morozov Children’s Municipal Clinical Hospital, Russian Federation;
Lyudmila M. Kuzenkova, MD, PhD, DSci., Prof., Head of the Center for Child Psychoneurology, Head of the Department of Psychoneurology and Psychosomatic Pathology of the National Medical Research Center for Children’s Health; prof. of the Department of pediatrics and pediatric rheumatology of the Sechenov First Moscow State Medical University, Russian Federation;
Svetlana V. Mikhailova, MD, PhD, DSci., Professor of the Department of neurology, neurosurgery and medical genetics named after Badalyan, Faculty of Pediatrics, Professor of the Department of general and medical genetics, Faculty of Medicine and Biology, Head of the Department of medical genetics of the Russian Children’s Clinical Hospital of the N.I. Pirogov Russian National Research Medical University, Russian Federation;
Kristina S. Nevmerzhitskaya, MD, PhD, Assistant of the Department of nervous diseases, Ural State Medical University, Head of the Department of neurology, Sverdlovsk Region Clinical Hospital, Russian Federation;
Tatyana M. Pervunina, MD, PhD, DSci., Director of the Institute of Perinatology and Pediatrics named after V.A. Almazov, Russian Federation;
Sofia G. Popovich, junior researcher, Department of psychoneurology and psychosomatic pathology, National Medical Research Center for Children’s Health, Russian Federation;
Irina B. Sosnina, chief physician of the St. Petersburg Consultative and Diagnostic Center for Children, chief freelance children’s specialist neurologist of the Committee on Health of St. Petersburg, Russian Federation;
Eugeniya V. Uvakina, junior researcher, Department of psychoneurology and psychosomatic pathology, National Medical Research Center for Children’s Health, Russian Federation;
Lyudmila M. Shchugareva, MD, PhD, DSci., Professor of the Department of pediatric neuropathology and neurosurgery, North-Western State Medical University. I.I. Mechnikov, head of the Department of neurology, St. Petersburg Children’s City Multidisciplinary Clinical Specialized Center for High Medical Technologies, Russian Federation

Introduction. Mucopolysaccharidosis type II (MPS II, Hunter syndrome)  (mucopolysaccharidosis type II, MPS II) is a progressive multisystem disorder. Neurodegenerative course characterizes the severe (neuronopathic) form of MPS II. Pathogenetic therapy for the severe form of the disease is under development, and symptomatic neurological treatment is to be improved. Natural history data are required for rationalization of symptomatic care and assessment of emergent treatment effectiveness.

The aim of the study. To describe the course of neurodegenerative disease in children with neuronopathic form of MPS II.

Materials and methods. Fifty eight boys with established diagnosis of MPS II were included in the study. The course of  the disease  in 42 patients was classified as neuronopathic. Data on complaints, anamnesis and neurological examination obtained from medical documentation and within the framework of this study, as well as descriptions of video-EEG monitorings, performed in  National Medical Research Center of Children’s Health, were used.

Results. The spectrum and chronology of neurological symptoms in children with severe Hunter syndrome were described. 64% of patients were found to achieve the level of phrasal speech at any time of the development. Laughter or crying paroxysms in children with neuronopathiс MPS II were judged to be a manifestation of pseudobulbar affect. Burden of sleep disorder was demonstrated to increase through the course of the disease. Absence of epileptic seizure was significantly more frequent than epilepsy manifestation during the first two years after epiactivity appears on EEG (75 vs 25%; p = 0.046).

Conclusion. Obtained natural history descriptions of severe MPS II cases are intended to be used in optimization of neurological care for patients and in assessment of emergent treatments’ effectiveness in real clinical practice.

Contribution: 
Osipova L.A. — concept; complaints and anamnesis data collection; neurological examination; data processing and analysis; text writing; text editing;
Kuzenkova L.M. — concept; text editing; 
Podkletnova T.V. — concept; complaints and anamnesis data collection; text editing.
All co-authors — are responsible for the integrity of all parts of the manuscript and approval of its final version.

Acknowledgements. The study had no sponsorship.

Conflict of interest. The authors declare participation in educational activities with the support of Takeda Pharmaceutical Company.

Received: May 4, 2023
Accepted:  May 23, 2023
Published: June 30, 2023

Introduction. Idiopathic generalized epilepsies account for approximately 15-20% of individuals with epilepsy. However, there is no consensus on how to cancel anticonvulsant therapy in patients with these epileptic syndromes after achieving remission, and what can be considered as risk factors for relapse of seizures.

Purpose: identification of predictors of seizure recurrence after discontinuation of anticonvulsant therapy in patients with idiopathic generalized epilepsy.

Materials and methods. Retrospective analysis of seizure recurrence after discontinuation of anticonvulsant therapy in patients with idiopathic generalized epilepsy. The analysis included two hundred thirty eight patients with genetic generalized epilepsy (GGE), of which 209 (88%) patients were with idiopathic generalized epilepsy (IGE) and 29 (12%) patients with GGE. 143 (68%) patients with IGE achieved remission. An attempt to cancel anticonvulsant was made in 78 (54%) patients.

Results. Seizure recurrence was observed in 57 (73%) patients. 90% of seizure relapses occurred in the first 5 years after discontinuation of therapy, half of the relapses occurred in the first year. In group of patients with childhood absence epilepsy (CAE), therapy was discontinued in 6 patients, relapse — 0. 8/14 (57,1%) patients with juvenile absence epilepsy (JAE) had relapse after therapy discontinuation. The relapse in patients with juvenile myoclonic epilepsy (JME) was 23/25 (92%) and in group of patients with isolated generalized tonic-clinic seizure (IGTCS) was in 26/33 (78,8%).

Conclusion. Among the epileptic syndromes included in the group of idiopathic generalized epilepsies, CAE has the most favourable prognosis after discontinuation of anticonvulsant therapy, and JME has the least, with a recurrence risk of more than 90%.

Contribution. Each author made an equal contribution to the writing of the article. All co-authors are responsible for the integrity of all parts of the manuscript and approval of its final version.

Compliance with ethical standards. The study does not require the submission of the opinion of the biomedical ethics committee or other documents.

Acknowledgements. The study had no sponsorship. We express our gratitude to Alexandra Demidova for her contribution to the statistical processing of the obtained data.

Conflict of interest. The authors declare no conflict of interest.

Received: April 10, 2023
Accepted:  May 23, 2023
Published: June 30, 2023

The fetal environment and circulatory patterns are very different from that of extrauterine life. The fetus evolved to thrive and grow in a relative hypoxemic environment adapted several mechanisms in response to changes in oxygen concentration in the blood to ensure optimal oxygen delivery to the brain and heart. However according to estimates of the World Health Organization in the world from 4 to 9 million newborns are born annually in a state of perinatal asphyxia. In economically underdeveloped countries, this indicator is higher than in developed countries, but in general, the frequency of perinatal asphyxia remains at a rather high level in the modern world. Perinatal asphyxia or hypoxic-ischemic encephalopathy, in newborns can cause multiple organ dysfunction in the neonatal period, severe diseases in the future, lead to disability and infant mortality. Perinatal asphyxia is characterized by a violation of gas exchange, which can lead to varying degrees of hypoxia, hypercapnia and acidosis, depending on the duration and degree of interruption of air flow, however, obstructed perinatal gas exchange does not have precise biochemical criteria. In addition, the exact mechanisms of pathophysiology of perinatal asphyxia have not been fully studied, as a result of which the “gold standard” of treatment remains an active area of research. The publication reflects modern views on the main stages of the pathogenesis of perinatal asphyxia, shows changes in blood circulation during delivery and the neonatal period, presents current data on emerging disorders in the newborn’s body against the background of hypoxic ischemic encephalopathy.

Contribution:
Petrova A.S. — concept, writing text;
Zubkov V.V. — concept;
Zakharova N.I. — editing;
Lavrent’ev S.N. — writing text;
Kondrat’ev M.V. — writing text;
Gry‘zunova A.S. — writing text;
Serova O.F. — editing.
All co-authors are responsible for the  integrity of all parts of the manuscript and approval of its final version.

Acknowledgements. The study had no sponsorship.

Conflict of interest. The authors declare no conflict of interest.

Received:  May 4, 2023
Accepted:  May 26, 2023
Published: June 30, 2023

Wieacker–Wolff syndrome (WWS) (OMIM 314580, 301041) is rare, slowly progressive, X-linked hereditary disorder. It is characterized by fetal akinesia, which results in congenital multiplex arthrogryposis, spasticity, and development delay. WWS is caused by the point mutations or extended deletions in the ZC4H2 gene, located on the long arm of the X chromosome (Xq11.2). Currently, about 100 cases have been described.

We present the case of WWS 5-year girl. DNA diagnostic was performed using full exome sequencing and confirmed by Sanger sequencing. Determination of non-random X-chromosome inactivation was performed by methyl-sensitive PCR of GAAA-repeat RP2 gene. 

The main clinical symptoms in our case are stiffness of large and small joints, specific facial phenotype, spasticity and lack of independent walking. We revealed  heterozygous mutation с.22_23delAT (p.Met8fs) in ZC4H2 gene. Non-random inactivation of the X chromosome was detected (XCI = 96.1%).

Conclusions. Clinical symptoms of the disease, the nature of the detected mutation and the literature data indicate to the presence of an X-linked dominant pattern of inheritance of WWS in our patient. We described the case referred to the group of ZC4H2-associated rare disorders.

Contribution:
Kondakova O.B. — concept, writing text, editing text;
Kuzenkova L.M. — concept, editing text;
Lyalina A.A. — writing text; editing text;
Nezhelskaya A.A. — writing text; editing text;
Davydova Yu.I. — design of demonstrating materials, writing text;
Grebenkin D.I. — design of demonstrating materials, writing text;
Zhanin I.S. — writing text, editing text;
Alekseeva E.A. — conducting laboratory molecular genetic diagnostics, editing text;
Kanivets I.V. — conducting laboratory molecular genetic diagnostics, editing text;
Pushkov A.A. — writing text, editing text.
All co-authors are responsible for the integrity of all parts of the manuscript and approval of its final version.

Acknowledgements. The study had no sponsorship.

Conflict of interest. The authors declare no conflict of interest.

Received: April 15, 2023
Accepted: May 22, 2023
Published: June 30, 2023

Propionic aciduria (PA) is an autosomal recessive hereditary disease from the group of organic aciduria, caused by a deficiency of propionyl-CoA carboxylase, leading to impaired metabolism of methionine, threonine, valine, isoleucine, and fatty acids with an odd number of carbon atoms and cholesterol. The neonatal form of PA manifests itself during the first week of life, is characterized by an acute onset and a crisis course, which is accompanied by severe metabolic acidosis, hypoglycemia, hyperketonemia, hyperammonemia. Clinical symptoms are dominated by neurological disorders up to stupor or coma, which can lead to death. Since 2023, expanded neonatal screening has been introduced throughout the Russian Federation, which includes 36 groups of nosologies, as well as a number of hereditary metabolic diseases. Despite the inclusion of this pathology in expanded neonatal screening, doctors’ awareness of clinical manifestations and necessary therapy remains insufficient. Often such patients are diagnosed with, for example: hypoxic-ischemic damage to the central nervous system, acute meningoencephalitis, and others, which leads to inadequate therapy with the development of fatal neurological consequences. Therefore, the totality of knowledge and alertness of doctors regarding diseases from the group of hereditary metabolic diseases will help not only to suspect this pathology in a timely manner, but also to prescribe adequate therapy in time, which in the future will make it possible to prevent serious consequences and neurological disorders, as well as disability of patients.

Contribution:
Sokolova A.V. — concept, text writing;
Bushueva T.V. — correction diet therapy, concept, text editing;
Kuzenkova L.M. — concept, text writing;
Borovik T.Е. — concept, text writing;
Globa O.V. — concept, text writing;
Podkletnova T.V. — concept, text writing;
Lyalina A.A. — concept, text writing;
Pushkov A.A. — conducting molecular genetic diagnostics, analysis and processing of the results of molecular genetic diagnostics;
Mazanova N.N. — conducting molecular genetic diagnostics, analysis and processing of the results of molecular genetic diagnostics;
Savosl’yanov K.V. — analysis and processing of the results of molecular genetic diagnostics;
Zakharovа E.Yu. — conducting molecular genetic diagnostics, analysis and processing of the results of molecular genetic diagnostics;
Aksyanova K.F. — primary examination, observation of the child at the place of residence;
Khamidova M.M. — design, editing the article;
Khubieva M.U. — design, editing the article.
All co-authors are responsible for the integrity of all parts of the manuscript.

Acknowledgements. The study had no sponsorship.

Conflict of interest. The authors declare no conflict of interest.

Received:  May 15, 2023
Accepted:  May 26, 2023
Published: June 30, 2023