Introduction. Bronchopulmonary dysplasia (BPD) is a complex disease with a significant genetic predisposition. The aim of the study was to determine genetic markers associated with the development of bronchopulmonary dysplasia in premature infants.

Materials and methods. At Stage 1, whole exome sequencing followed by the bioinformatic analysis of one hundred samples was provided to evaluate the genetic variants. Sequencing data were compared with the data of the children without any congenital pulmonary diseases. At Stage 2, the obtained results were validated using real-time PCR. Further the genotyping of the control group (n = 70) was performed. The obtained frequencies of nucleotide variants were compared between the groups, as well as with general population data using the RUSeq database.

Results. The prevalence of genetic variant rs12489516 in gene CPA3 was significantly higher in the control group of premature infants (p = 0.03; OR = 0.2; 95% CI: 0.02–0.94). Its presence in the genotype reduces the likelihood of developing BPD by 4.76 times. Moreover, statistically significant differences were also identified in the prevalence of rs45488997 in gene CCN2 (p = 0.023). This genetic variant was specific only for children with bronchopulmonary dysplasia. It was also identified that the prevalence of the nucleotide variant rs45488997 in the CCN2 gene was statistically more common among patients with bronchopulmonary dysplasia compared with the general population (p = 0.005). In addition, genetic variants rs5744174 in gene TLR5 and rs2476601 in gene PTPN22 were less frequently observed in the investigated group compared to the general population (p = 0.03 and p = 0.003, respectively).

Conclusion. Identification of genetic markers together with clinical and laboratory data will contribute to the development of an effective predictive model for the calculation of the probability of BPD.

Contribution:
Fisenko A.P. — development of research concept and design, text editing;
Basargina M.A. — development of research concept and design;
Sevostyanov K.V. — development of research concept and design, text editing;
Pushkov A.A. — development of research concept and design;
Davydova I.V. — development of research concept and design, text editing;
Basargina M.A. — collection and processing of data, statistical processing of material and writing text;
Bondar V.A. — data collection and processing; statistical processing of material and writing text;
Zhanin I.S. — performing laboratory research, statistical processing of material.
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 1, 20244

Accepted: March 28, 2024

Published: April 27, 2023

Introduction. Brain–lung–thyroid syndrome (BLTS, choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction) is an autosomal dominant disorder associated with mutations of the NKX2-1 gene. A triad of symptoms from three organs (brain, lungs, thyroid gland) is manifested in 50% of patients, in other cases there is an incomplete phenotype of the disease. The most common manifestations are neurological. The aim of the study was to provide genetic, clinical, laboratory, and instrumental characteristics in BLTS patients with a clinical and morphological assessment of the phenotype.

Materials and methods. Ten children from 9 families with identified mutations in the NKX2-1 gene were observed. Methods used: genealogical, Sanger sequencing, clinical and morphological assessment of the phenotype, examination of thyroid hormone levels, CT, MRI of the brain, CT of the chest, lung biopsy.

Results. The article presents the results of molecular genetic analysis, family history, age of manifestation and diagnosis. 9 out of 10 children had damage to the central nervous system, thyroid gland, lungs, and one child had a combination of neurological pathology and hypothyroidism. Neurological pathology was represented by benign hereditary chorea (2 children), delayed motor development (8), muscular hypotension (7), ataxia (5), choreoathetosis (1), clonuses (1), seizures (1), hyperkinesis (3); respiratory — respiratory distress syndrome (RDS) of newborns (6), chronic respiratory failure (5), interstitial lung disease (6), bronchial asthma (1), chronic pneumonitis of infants (1), bronchiectasis (1). There are presented changes in computed tomograms of the lungs and during preforming CT, MRI of the brain. Typical developmental microanomalia included a protruding forehead, a wide tip of the nose, elongated narrow palpebral fissure, deep-set eyes, hypertelorism of the eyes, large rotated low-lying auricles, conical fingers.

Conclusion. A combination of congenital hypothyroidism, neonatal RDS, heart disease, neurological disorders (hypotension, ataxia, delayed motor development, chorea), craniofacial dysmorphia is the basis for a molecular genetic examination to exclude BLTS.

Contribution:
Strelnikova V.A. — text writing, material collection and data processing, review of publications on the topic;
Ovsyannikov D.Yu. — patient management, text writing, material collection and data processing, concept, text editing;
Kondakova O.B. — concept, writing of the text, clinical and morphological assessment of the phenotype of patients, review of publications on the topic;
Kuzenkova L.M. — text editing, patient management, assessment of the neurological status of patients;
Savostyanov K.V. — analysis of the results of molecular genetic diagnostics, concept, text editing;
Gitinov S.A. — patient management, material collection and data processing;
Girutskaya I.V. — patient management, material collection and data processing;
Gorev V.V. — patient consultation, the concept of the article;
Zhestkova M.A. — patient consultation, material collection and data processing, review of publications on the topic;
Kravchenko N.E. — patient consultation, material collection and data processing;
Mamaeva E.A. — evaluation of neuroimaging results, text writing, material collection and data processing;
Mezhinsky S.S. — patient management, material collection and data processing;
Nikolishin A.N. — patient consultation, material collection and data processing;
Orlov A.V. — patient management, material collection and data processing;
Pushkov A.A. — conducting molecular genetic diagnostics, analysis and processing of the results of molecular genetic diagnostics;
Sudakova O.V. — patient management, material collection and data processing;
Suetina O.A. — patient consultation, material collection and data processing;
Tsverava A.G. — patient management, material collection and data processing;
Afukov I.I. — organization of medical care for patients;
Cherkasova S.V. — patient management, text writing, material collection and data processing.
All co-authors — approval of the final version of the article, responsibility for the integrity of all parts of the article.

Acknowledgements. The study had no sponsorship.

Conflict of interest. The authors declare the absence of obvious and potential conflicts of interest in connection with the publication of this article.

Received: February 16, 2024
Accepted: March 15, 2024
Published: April 27, 2023

Introduction. Speech disorders are a common problem in childhood. Speech disorders of various types are, in particular, the most common complications of epilepsy.

Objective. The clinical manifestations of speech disorders in children with epileptic encephalopathies were studied.

Materials and methods. The study included eighty nine children with epileptic encephalopathies. All patients underwent a detailed study of the anamnesis of life and disease, assessment of neurological and somatic, analysis of the semiotics of seizures, assessment of the therapy received, articulatory praxis, phonemic perception, game activity, expressive speech, impressive speech.

Results. Speech in the examined patients had the character of a gross violation after the stage of normal development (37.1%), speech development delay was noted in 38.2% of patients from birth. Phonemic perception was impaired in 73 (82.0%) patients, a violation of articulatory praxis was detected in 63 (70.8%) patients, coherent speech was not formed in 78 (87.6%) patients, play activity did not correspond to the age of the child in 50 ( 56.2%) cases, violation of the account was detected in 69 (77.5%) patients, violation of sound pronunciation was observed in 30 (33.7%) patients.

Conclusion. Articulatory apraxia and motor alalia are the most common types of speech disorders in children with epileptic encephalopathies.

Compliance with ethical standards. The study was conducted with the informed consent of parents and legal representatives of the patients. The research protocol was approved by the Ethics Committee of the St. Petersburg State Pediatric Medical University (protocol No. 04/06 of November 11, 2021).

Сontributions:
Guzeva V.I. — concept and design, text writing, editing;
Eremkina Yu.A. — concept and design, text writing, editing;
Guzeva O.V. — text editing;
Guzeva V.V. — concept, text editing;
Okhrim I.V. — text editing;
Vedernikova V.A. — text writing.
All co-authors approval of the final version of the article, responsibility for the integrity of all parts of the article.

Acknowledgements. The study had no sponsorship.

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

Received: November 23, 2023
Accepted: February 16, 2024
Published: April 28, 2024

Duchenne muscular dystrophy (DMD) is the most common lumbar-limb muscular dystrophy with an X-linked recessive type of inheritance. It is characterized by a debut at an early age, rapidly progressive atrophy of the striated musculature of the limbs, trunk, heart muscle, which leads to loss of motor skills, severe cardiovascular and respiratory complications.

Currently, a number of new drugs have appeared for the pathogenic therapy of MDD, the effectiveness of which is the most during its early initiation in the ambulatory stage of the disease. One of the new methods of MDD treatment is antisense oligonucleotide therapy. The application of this type of therapy is possible for certain mutations in the DMD gene and is recommended immediately after diagnosis. At the moment, the duration of this method of treatment in the Russian Federation is only a few years.

In our article we discuss a clinical case of the study of a patient suffering from Duchenne muscular dystrophy caused by the deletion of 50–52 exons in the DMD gene, who is on therapy with steroids and Viltolarsen.

A special feature of the case is the late application of Viltolarsen from the age of 9 years. The results of the observation demonstrate a significant effect in stabilization of motor skills, of the functioning of the cardiovascular and respiratory systems, which gives a chance to slow down the course of the disease, improve the quality of life and increase its duration, even taking into account the late initiation of pathogenic therapy.

Contribution:
Kuzenkova L.M. — concept and design of the study, writing the text, editing;
Podkletnova T.V. — concept and design of the study, writing the text, editing;
Uvakina E.V. — concept and design of the study, writing the text, editing;
Popovich S.G. — editing;
Andreenko N.V. — editing;
GlobA O.V. — editing.
All authors approval of the final version of the article, responsibility for the integrity of all parts of the article.

Acknowledgements. The study had no sponsorship.

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

Received: March 1, 2024
Accepted: March 30, 2024
Published: April 27, 2024

Neurodevelopmental disorder without speech and variable seizures (NEDALVS) is a rare autosomal dominant inherited disorder, characterized by motor development delay, mental retardation, wide-based gait, autism spectrum disorders and seizures.

Currently, fifteen cases of NEDALVS have been described worldwide.

NEDALVS caused by mutations in the WASF1 gene, located on the long arm of chromosome 6. Nonsense-, missense-, frameshift mutations and large deletion have been described in WASF1 gene.

We present the clinical case of 9-year monozygotic NEDALVS twins, accompanied by cerebral pachygyria/polymicrogyria. DNA diagnostic was performed using full genome sequencing, followed by validation using Sanger sequencing. A previously described heterozygous pathogenic variant c.1516C>T (p.R506*) in the WASF1 gene was identified.

We performed the results of a comparative analysis based on the literature and our patients. All patients had delayed motor and psycho-speech development, severe mental retardation was in 53% of cases, lack of speech — 18%, autistic manifestations and seizures — 41%, wide-based gait — 29%, strabismus and feeding problems — 35%.

Conclusion. WASF1 gene mutations caused a rare form of mental retardation in children. We present the first case of NEDALVS in Russian Federation and the world’s first description of pachygyria in patients, caused by WASF1 gene mutations. The use of NGS as a first-line test for research and diagnostic of neurodevelopmental disorder is determined by their non-specific clinical features.

Compliance with ethical standards. Informed voluntary consent was obtained from the parents of the patients for the publication of photographic materials.

Contribution:
Kondakova O.B. — concept, writing text, editing;
Gudkova A.P. — writing text, design of demonstrating materials, editing;
Grebenkin D.I. — design of demonstrating materials, writing text;
Demyanov S.V. — writing text, editing;
Davydova Iu.I. — writing text, editing;
Lyalina A.A. — design of demonstrating materials, writing text;
Kanivets I.V. — conducting laboratory molecular genetic diagnostics, editing;
Zhanin I.S. — conducting laboratory molecular genetic diagnostics, editing;
Pushkov A.A. — writing text, editing;
Savostyanov K.V. — writing text, editing.
All co-authors approval of the final version of the manuscript, responsibility 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: January 30, 2024
Accepted: February 16, 2024
Published: April 27, 202

Progressive Duchenne muscular dystrophy (DMD) (OMIM # 310200) is an inherited X-linked neuromuscular disease caused by a mutation in the DMD gene encoding the dystrophin protein, resulting in absent or deficient dystrophin function. It usually affects boys during childhood. Among mutations, large deletions are found in ~65% of cases; ~10% of mutations are represented by duplications, and the remaining cases are represented by point and small mutations, of which 10–15% are represented by nonsense mutations (stop mutation). Currently, pathogenetic therapy is available for a number of deletions and point nonsense mutations in this gene. Translarna® (ataluren) is the only drug for pathogenetic therapy of patients with DMD caused by nonsense mutations registered in the Russian Federation. We present a clinical case of the earliest and long- lasting effective treatment with Translarna® (ataluren) in a boy born in 2016 in St. Petersburg.

Contribution:
Snegova E.V. — concept, writing text, editing;
Oshchenkova N.A. — writing text;
Glebovskaia O.I. — writing text;
Sosnina I.B. — editing.
All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version.

Acknowledgement. The study had no sponsorship.

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

Received: February 6, 2024
Accepted: March, 6, 2024
Published: April 27, 2024