Introduction. Pathogenic variants of the FLNA gene cause damage to various organs and systems formed in the embryonic period. The most frequently affected organs are the brain (epilepsy), cardiovascular system (congenital heart defects, pulmonary hypertension — PH), and lungs (emphysema).

The aim of the study: genetic, clinical, laboratory, and instrumental characteristics of patients with a disease caused by pathogenic variants of the FLNA gene.

Materials and methods. Six girls with identified pathogenic variants of the FLNA gene were observed. The methods used: genealogical, whole exome sequencing, Sanger sequencing, electroencephalography, brain MRI, echocardiography, right heart catheterization with determination of pressure and resistance in the pulmonary circulation and pulmonary capillary wedge pressure, CT of the chest organs.

Results. The article presents the results of a molecular genetic study of the FLNA gene. All patients were diagnosed with periventricular nodular heterotopia and psychomotor retardation, 2 of them had epilepsy; 4 children had heart valve dysplasia; 3 had patent ductus arteriosus, 3 had septal defects, 2 had bicuspid aortic valve, 5 had pulmonary hypertension; 5 had pulmonary emphysema; 1 had congenital diaphragmatic hernia. Two patients died during the observation period.

Conclusion. Diagnosis and observation of patients with pathogenic variants of the FLNA gene is a challenge for a multidisciplinary team of doctors at a multidisciplinary pediatric hospital. The presented cohort of 6 patients reflects the most typical manifestations of this pathology, the severity and rate of development of disease in infants.

Compliance with ethical standards. The study was conducted in accordance with the Helsinki Declaration (2013) and Federal Law No. 152-FZ of July 27, 2006 (as amended on December 31, 2017) “On Personal Data”. Voluntary written informed consent was obtained from the patients’ legal representatives.

Contribution:
Miroshnichenko V.P. — patient management, text writing, material collection and data processing, reviewing publications on the topic;
Ovsyannikov D.Yu. — patient management and consultations, text writing, material collection and data processing, concept, text editing;
Abramyan M.A. — patient management, concept, text editing;
Kuzenkova L.M. — text editing, patient management, assessing the neurological status of patients;
Aisina V.A. — analysis and interpretation of electroencephalography data, collecting material and processing data;
Boytsova E.V. — reviewing publications on the topic;
Gitinov Sh.A. — patient management, material collection and data processing;
Gneusheva O.A. — patient management, material collection and data processing;
Gorbunov A.V. — neuroimaging results assessment, material collection and data processing;
Gorev V.V. — medical care organization for patients;
Ivanova A.V. — patient management, material collection and data processing;
Kovalev I.A. — patient consultation, material collection and data processing, medical care organization for patients;
Kondakova O.B. — patient consultation, material collection and data processing;
Kotlukova N.P. — patient consultation, concept, material collection and data processing;
Kravchenko N.E. — review of publications on the topic;
Kuznetsova A.A. — patient consultation, material collection and data processing;
Lyalina A.A. — text editing, assessment of neurological status and phenotype of patients;
Miklashevich I.M. — patient management, material collection and data processing;
Petrova S.I. — patient consultation, material collection and data processing;
Pushkov A.A. — molecular genetic diagnostics, analysis and processing of molecular genetic diagnostics results;
Simonova O.I. — patient consultation, material collection and data processing;
Solomatina N.M. — patient management, material collection and data processing;
Strelnikova V.A. — material collection and data processing;
Suetina O.A. — review of publications on the topic;
Telezhnikova N.D. — patient management, material collection and data processing;
Trunina I.I. — patient consultation, material collection and data processing;
Savostyanov K.V. — analysis and processing of molecular genetic diagnostics results, concept, text editing.
All co-authors — responsibility for theintegrity 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 22, 2025
Accepted: May 28, 2025
Published: August 20, 2025

Introduction. RASopathy pathologies are a unique group of diseases with a multisystem lesion. In the structure of RASopathy, causal genetic variants of the RAF1 are the most common cause of HCM. Among all registered variants of the RAF1, the variant c.770C>T, p.S257L accounts for approximately 50% of cases. Due to the heterogeneity of clinical manifestations in patients with pathogenic variants of the RAF1 gene, the establishment of clinical and genetic features remains an urgent task.

The aim of the study. To establish clinical and molecular genetic characteristics of Russian children with Noonan syndrome caused by variants of the RAF1 gene.

Materials and methods. Single-center retrospective and prospective cohort study of a sample of ninety eight RASopathy patients aged from 1 month to 18 years.

Results. In 19 of 98 patients with RASopathy, there were detected causal variants in the RAF1 gene, which amounted to 19.0%. All genetic variants detected in the RAF1 gene are localized in the cluster part of the gene in the CR2 domain. The c.770C>T, p.S257L variant was the cause of the disease in 10.22% of cases of all RASopathy diagnosed by us and 52.6% of cases of all children with RAF1 gene variants. All patients with RAF1 gene variants showed characteristic extracardiac signs of Noonan syndrome from the first months of life. Myocardial hypertrophy (MCH) was present in all patients, in the vast majority (89.4%) — with LVOT obstruction. When analyzing the course of remodeling, cases of MCH progression were more often noted (78.9%). In 35.7% of patients, one of the adverse cardiovascular events was recorded.

Patients with the c.770C >T, p.S257L variant, compared with patients with other genetic variants, already from the first hospitalization demonstrated a more severe phenotype with pronounced signs of HF (p = 0.104), the highest level of NTproBNP (p = 0.003) and LVOTO (p = 0.040).

Conclusion. RAF1 gene variants children demonstrate the classic phenotype of Noonan syndrome with the most severe damage to the cardiovascular system and require a comprehensive and dynamic examination with the involvement of specialists of various profiles.

Compliance with ethical standards. The study was approved by the Local independent ethics committee at the National Medical Research Center for Children’s Health of the Ministry of Health of the Russian Federation (protocol No. 4 dated 04/28/2022).

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

Funding. The study had no sponsorship.

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

Received: June 3, 2024
Accepted: July 10, 2024
Published: August 20, 2025

Introduction. Neuralgias in military personnel represent a pressing medical and social issue, as chronic neuropathic pain significantly reduces combat readiness, physical performance, and the quality of life of service members. The aim of this study was to examine the clinical characteristics, diagnostic methods, treatment, and prevention of various types of neuralgias (trigeminal, postherpetic, occipital, intercostal, sciatica, and others) in military personnel. The study included one hundred twenty cases recorded at the Military Educational and Scientific Center of the Air Force from 2018 to 2023.

Materials and methods. A retrospective analysis was conducted to assess clinical manifestations, etiology, diagnostic procedures (neurological examination, MRI, CT, electroneuromyography, diagnostic nerve blocks), as well as treatment outcomes and preventive measures.

Results. The most frequently diagnosed types were sciatica (33.3%) and occipital neuralgia (20.8%). Chronic pain lasting more than 3 months was observed in 30% of patients. Standard first-line therapies (carbamazepine, gabapentin, pregabalin, amitriptyline, duloxetine) led to complete remission in 67% of cases and partial improvement in 29%. In treatment-resistant cases, physiotherapy, botulinum toxin injections, and neurosurgical interventions were employed. Preventive measures included Varicella Zoster virus vaccination, regular medical check-ups, health education, and improvements in the ergonomic design of military equipment.

Conclusion. The implementation of modern approaches to the diagnosis and treatment of neuralgias at the Military Educational and Scientific Center of the Air Force ensures high effectiveness of medical care: over 90% of servicemen returned to duty after treatment. Prospects for improvement include the establishment of specialized centers in military hospitals, the development of departmental clinical guidelines for neuropathic pain treatment, training of medical personnel in early detection and multidisciplinary management of patients with neuralgia, as well as further exploration of new methods (gene therapy, neuromodulation) for patients with refractory pain.

Compliance with ethical standards. All participants in the study provided voluntary informed consent.

Contribution:
Skripnikova A.A. — concept, writing, and editing of the manuscript.

Conflict of interest. The author declares no conflict of interest.

Funding. The study had no sponsorship.

Received: April 30, 2025
Accepted: May 28, 2025
Published: August 20, 2025

Currently, Russian-manufactured generic products are being actively implemented into the clinical practice in the Russian Federation, including spinal muscular atrophy treatment. This article presents five clinical cases with various types of spinal muscular atrophy treatment with generic Russian nusinersen, both naive and those who had previously received therapy with the reference drug nusinersen and continued therapy with generic nusinersen. The trend in motor activity in patients during treatment, assessed by motor development scales, is presented. In all of 5 described clinical cases both the positive effect and favorable safety profile of the Russian-manufactured generic nusinersen were demonstrated.

Compliance with ethical standards. All patients or their legal representatives signed voluntary informed consent.

Contributions:
Kuzenkova L.M. — concept and design of the review, writing the text, editing;
Uvakina E.V. — concept and design of the review, writing the text, editing;
Serebrennikova E.B. — writing the text, editing;
Karpovich E.I. — writing the text, editing;
Samofal T.A. — writing the text, editing;
Lapochkin O.L. — writing the text, editing;
Smirnova A.A. — writing the text, editing;
Golenko A.A. — writing the text, editing.
All co-authors — responsibility 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: July 22, 2025
Accepted: August 5, 2025
Published: August 20, 2025

Pallister–Killian syndrome (tetrasomy 12p, mosaic isochromosome 12p syndrome) (OMIM#601803) is a rare genetic disease characterized by multiple developmental abnormalities and mental retardation. The frequency of occurrence is 5.1:1,000,000. Newborns with this syndrome are characterized by muscular hypotension, which causes children to experience breathing difficulty and feeding problems, craniofacial dysmorphic disorder: a “rough” face — a high protruding forehead, oblique eye slits with epicanthus, hypertelorism, a wide and flattened nose with turned-out nostrils, low-set and dysplastic ears, micrognathia, a wide mouth with an inverted lower lip, a thin upper lip in the shape of a Cupid’s bow. Most children have a high hairline, bilateral frontal-temporal alopecia, sparse eyebrows or eyelashes, and areas of hypopigmentation in the form of light spots or streaks. The neurological status most often shows a serious delay in the pace of speech, motor, and intellectual development, although a more “mild” course of the disease is described. Specific speech disorders are also characteristic.

To verify the diagnosis, the child needs to examine the buccal epithelium or fibroblasts using FISH analysis. The prognosis of the disease is unfavourable. It is also aggravated by the presence of profound intellectual disability and the possible development of seizures. Currently, no specific treatment for patients has been developed. Depending on the clinical manifestations, therapy may include surgical correction of the identified congenital disorders. One of the important stages of managing patients with such a diagnosis is working with psychologists and educators to support the intellectual development and socialization of the child.

The article presents a clinical case of managing a child with Pallister–Killian syndrome, as well as current views on the diagnosis of this disease.

Contribution:
Kharitonova N.A. — concept and design of the study, collection and processing of material, writing the text, editing;
Basargina M.A. — editing;
Vavilova N.V. — collection and processing of material;
Uvakina Ye.V. — collection and processing of material;
Nesterovich M.I. — collection and processing of material.
All authors — responsibility for the integrity of all parts of the manuscript and approval of its final version.

Acknowledgment. The study had no sponsorship.

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

Received: January 20, 2025
Accepted: February 7, 2025
Published: August 20, 2025