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.

Compliance with ethical standards. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the institution’s human research committee and was approved by the Ethics. The design of the study was approved by the ethics committee of the National Research Center for Children’s Health of the Russian Ministry of Health.

Contribution:
Gandaeva L.A. — concept, editing;
Kaverina V.G. — writing text;
Basargina E.N. — editing;
Pushkov A.A. — editing;
Savostyanov K.V. — concept, editing.
All co-authors are responsible for the  integrity of all parts of the manuscript and approval of its final version.

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

Acknowledgment. The study had no financial support. All authors are grateful to the patients and their families for their continuous contributions and support of our research. The authors express their gratitude to the director of the National Research Center for Children’s Health, professor A.P. Fisenko for support and technical assistance in the implementation of this work.

Received: June 28, 2023
Accepted: August 30, 2023
Published: October 13, 2023

Spinal muscular atrophy (SMA) is an autosomal recessive, disabling neuromuscular disease characterized by the death of motor neurons in the spinal cord, giving rise in the development both of muscle weakness and, subsequently, flaccid tetraparesis, swallowing and breathing disorders. There are 4 types of SMA, depending on the age of manifestation, the most severe is type I (not counting type 0 — prenatal type).

Modern diagnosis of SMA includes a molecular genetic study looking for mutations in the SMN1 gene and determining the copy number of the SMN2 gene. Instrumental and biochemical methods for evaluating the effectiveness of therapy for spinal muscular atrophy are currently under study. Neurofilament proteins have been investigated as potential biomarkers for several diseases characterized by axonal damage and degeneration. In clinical studies, there are isolated data on the use of blood neurofilaments as markers of SMA. This review considers the literature data of foreign authors and clinical studies of neurofilaments as perspective biomarkers of SMA, both heavy and light chains.

Contribution:
Fisenko D.A. — concept and design of the review, writing the text, editing;
Kuzenkova L.M. — concept and design of the review, editing;
Kurenkov A.L. — concept and design of the review, editing;
Uvakina E.V. — concept and design of the review, editing;
Popovich S.G. — concept and design of the review, 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: June10, 2023
Accepted: August 30, 2023
Published: October 13, 2023

Cerebral tumors are among the most menacing pathologies occurring in children. Of all the cerebral tumors, posterior cranial fossa tumors have been most widespread in children. The review of literature provides a detailed description of clinical pattern. The sources related about earlier occurrence of non-focal symptoms, rather than focal signs: lack of energy, nausea, vomiting and headache. The authors provided detailed description of cerebellum damage in case of tumors, and split the symptoms of the hemisphere and vermis injuries as ataxy and typical cerebellar gait are common to spot the malignant process in the vermis, whereas dyssynergia and hypomyotonia occur in case of hemisphere damage. The clinical picture of hydrocephalus in tumor pathology of posterior cranial fossa is discussed: rapidly growing child head circumference, separation of cranial sutures, bulging of fontanelle, child restless behavior, and other signs. The need for CT and MRI was substantiated as the most important diagnostic techniques; the benefits of each were also stated. Discussion was given to the clinical pattern of hydrocephalus in tumor pathology of the posterior cranial fossa, and the authors put special emphasis on the significance of presurgical correction of hydrocephalus. The authors mentioned the use of a neuronavigation system during surgical intervention and characterized the major accesses (access via the median aperture, transvermial, telovelar access) and methods of craniotomy, indications for resection and osteoplastic trepanation. This article discussed the basic principles of radio and chemotherapy used to achieve a sustained remission, approximate treatment patterns for various posterior cranial fossa tumors are described. In addition, the authors mentioned the need for MRI with contrast agent each 3 months, and subsequent visits to the specialist in oncology.

Contributions:
Ngankam Leon — concept, writing the text, text editing.
Dolgopolov I.S. — concept, writing the text.
Chichanovskaya L.V. — text editing.
Guseva E.V. — writing the text.
All the coauthors — approval of the article final version, responsibility for integrity of all the article parts.

Acknowledgements. The study had no sponsorship.

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

Received: July 04, 2023
Accepted:  August 30, 2023
Published: October 13, 2023

Introduction. Spinal muscular atrophy (SMA) 5q is a rare genetically determined progressive neuromuscular disorder, is the most frequent cause of infant death not long ago. Nowadays onasemnogen abeparvovec as pathogenetic therapy is successfully used in clinical practice to combat this disease. Gene replacement therapy (GRT) with onasemnogen abeparvovec for SMA patients may come amid non-target changes in the cardiovascular system that require early diagnosis and monitoring.

Objective. To present clinical reports considering children with genetically confirmed SMA and elevated troponin I levels after onasemnogen abeparvovec gene replacement therapy.

Materials and methods. We monitored forty two children with genetically confirmed SMA who received gene replacement therapy with onasemnogen abeparvovec in the pediatric neurology department. All patients were tested for troponin I before and after the infusion, additional tests of N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP), creatine phosphokinase-MB (CPK-MB), electrocardiogram, echocardiography were made if needed.

Results. In 11 (26.2%) of 42 SMA children troponin I was elevated and detected up to the eighth week after drug administration. At the same time, an increased concentration of troponin I in the majority of cases (41 out of 42 children) was not associated with clinically significant manifestations. There was only one case when acute myocarditis, confirmed by clinical and instrumental methods of investigation occurred. It was a girl with a long-term (10 months) elevation of troponin I, who had an intercurrent infection.

Conclusions. Troponin I elevations detected after GRT with onasomnogene abeparvovec in SMA patients are often asymptomatic. This myocarditis case highlights the importance of longer cardiac monitoring of troponin I elevations, especially in the presence of intercurrent bacterial and viral infections.

Compliance with ethical standards. The study was approved by the Local Ethics Committee of the Pirogov Russian National Research Medical University, Ostrovitianov str. 1, Moscow, 117997, Russia (Protoсol No. 226 of 20.02.2023).

Contribution:
Papina Y.O. — research design, coordination of the study, material collection and data processing, text writing, review of publications on the topic of the article
Artemyeva S.B. — coordination of the study, obtaining data for analysis, analyzing the data obtained, article editing
Groznova O.S. — obtaining data for analysis, analyzing the data obtained, text writing
Lukyanova I.V. — obtaining data for analysis, analyzing the data obtained, text writing
Melnik E.A. — analyzing the data obtained, article editing
Tutelman K.M. — obtaining data for analysis, article editing
Vlodavets D.V. — coordination of the study, article editing

Acknowledgements. The study had no sponsorship.

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

Received: June 26, 2023
Accepted: August 30, 2023
Published: October 13, 2023

Wada test is an effective diagnostic method for determining the hemispheric localization of speech functions. The vast majority of epileptological centers use this technique in pre-surgical diagnosis in adult patients with medial temporal lobe epilepsy. According to international literature, the use of this test in the pediatric population is extremely rare due to the need for adequate contact with the patient. We present a clinical case of a patient with structural pharmacoresistant epilepsy caused by post-stroke changes in the left middle cerebral artery. Wada test was used as part of a pre-surgical examination to determine the lateralization of the patient’s speech function. The test results allowed determining the right hemisphere to be  dominant in speech function. After the surgical intervention — transylviar periinsular functional hemispherectomy — the girl had no deterioration in speech functions, which confirmed the specificity and sensitivity of the Wada test in a child with impaired cognitive development.

Contribution:
Russkin V.O. — concept, writing text, editing;
Kuznetsova A.A. — concept, writing text, editing;
Solovyov V.B. — concept, editing;
Levov A.V. — concept;
Schederkina I.O. — writing text, editing;
Livshits M.I. — concept.
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 12, 2023
Accepted: August 30, 2023
Published: October 13, 2023

A genetic disease caused by pathogenetic nucleotide variants in the SCN8A gene (Sodium channel protein type 8 subunit alpha, also known as Nav1.6), encoding the α-subunit of the Na channel type 8, is included in the group of early epileptic encephalopathies. In most cases, this pathology is characterized by the development of polymorphic pharmacoresistant epileptic seizures over the first year of a child’s life, a lag in psychomotor development or regression, loss of skills. In some patients, seizures may appear during the first days of life, while in others they appear later (at the age of 2 to 7 months), against the background of a pronounced or slight developmental delay. Types of seizures may include generalized, tonic-clonic seizures, infantile spasms, absences and focal seizures. Other signs and symptoms of encephalopathy caused by mutations of the SCN8A gene may include low muscle tone (hypotension), high pain threshold, motor disorders (such as dystonia and ataxia), mild to severe mental retardation, sleep problems and autistic traits. In some people with SCN8A encephalopathy, various other pathological changes in the body have been reported, including hearing or vision impairment, scoliosis, and thermoregulation difficulties. The disease is inherited by an autosomal dominant type.

To date, the disease in the OMIM system is referred to as «Developmental encephalopathy and epileptic encephalopathy type 13». Previously, the disease was called «Early infantile (infantile) epileptic encephalopathy, type 13». The serial number «13» indicates this form of early epileptic encephalopathy to be caused by a heterozygous mutation in the gene on the long arm of chromosome 12 in chromosome region 12q13.13.

This report also presents a clinical description of a patient suffering from early infantile epileptic encephalopathy, type 13.

Contribution:
Nikolenko D.S. — concept, text writing, text editing;
Zholudova A.A. — concept, text writing, text editing;
Globa O.V. — concept, text writing, text editing;
Kuzenkova L.M. — concept, text editing;
Savost’yanov K.V. — concept, text editing;
Buksh A.A. — concept.
All co-authors are responsible for the integrity of all parts of the manuscript and approval of its final version.

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

Acknowledgements. The study had no sponsorship.

Received:  May 15, 2023
Accepted:  August 30, 2023
Published: October 13, 2023

Sciatic neuropathy is rare and difficult to diagnose in pediatrics and often associated with difficult to control neuropathic pain. The most common causes of sciatic nerve damage in children include trauma and iatrogenic lesions, less often the cause is tumor and vascular formations, among which intraneural venous malformations are the rarest. We present a clinical case of a 13-year boy suffered from right sciatic pain neuropathy with unexpressed neuropathic pain syndrome, asymmetry of the feet, scant impairment of motor and sensory function of the limb for five years, which changed the  gait. Neurophysiological testing showed possible location of the process, an asymmetry of sensory and motor responses when testing the nerves of the legs, and abnormal EMG in sciatic-innervated muscles. The magnetic resonance imaging (MRI) showed focal enlargement of the right sciatic nerve in the pelvic region with enhancement upon administration of contrast. Due to the presence of pain in the limb and its forced position — bent at the knee joint, surgical treatment — endoneural neurolysis in combination with targeted therapy by immunosuppressant, was chosen as a therapeutic strategy. The histological study of the intraneural formation confirmed the presence of a venous malformation (VM) in the form of heterogeneous thick– and thin-walled vascular cavities by the presence of fibrosis and lymphocytic infiltration. The result of the treatment was the relief of neuropathic pain syndrome and the recovering of the child gait.

Compliance with ethical standards. Voluntary informed consent was obtained from the patient’s legal representative for treatment and publication of data.

Contribution:
Druzhinina E.S. — review of publications on the topic of the article, collection and analysis of data, writing the text of the manuscript;
Isaev I.V. — performing a surgical intervention, writing the text of an article;
Kostylev F.A. — data collection, writing the text of article;
Narbutov A.G. — performing a surgical intervention, writing the text of an article;
Zavadenko N.N. — writing the text of the article, checking critical intellectual content, final approval for publication of the manuscript.
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: March 13, 2023
Accepted:  March 27, 2023
Published: October 13, 2023