Nijmegen breakage syndrome in pediatric practice (literature review and personal observation)

Abstract

Background. Nijmegen breakage syndrome is a rare autosomal recessive disease characterized by microcephaly, specific facial features, immunodeficiency, and an increased susceptibility to malignancies.Purpose – is to highlight the importance of the pathology of Nijmegen breakage syndrome in pediatric practice, to demonstrate oneʼs own experience in a clinical case.Materials and methods. An analysis and generalization of the results of scientific research for 1985–2025, selected on the basis of an information search in the scien-tometric databases Scopus, Web of Science, PubMed, MEDLINE, Google Scholar using the keywords «Nijmegen breakage syndrome», «immunodeficiency», «clinical features», «laboratory features», «genotype», «phenotype», was carried out. The ma-jority of articles were represented by clinical studies and case presentations (73%). For the literature review, data were also obtained from sources containing literature reviews (27%). The most frequently cited sources in the article were from the years 2022–2024.Results and discussion. Nijmegen breakage syndrome is caused by mutations in the NBN gene, which encodes the protein nibrin, which is important for the repair of double-stranded DNA breaks. The most common mutation is a 5-base pair deletion (657del5), which leads to genomic instability and increased sensitivity to ionizing radiation. Parents of children with this syndrome are heterozygous carriers of the mutation, and the risk of having an affected child is 25% if both parents are carriers of the defective gene. Chromosomal instability with characteristic rearrange-ments of peripheral T-lymphocytes in the form of inversions and translocations invol-ving chromosomes 7 and 14, sensitivity of cells to ionizing radiation in vitro – all these are characteristic features of this disease that have important diagnostic value. Detection of mutations in both alleles of the nibrin gene is the final study in making the diagnosis. Most patients with Nijmegen breakage syndrome are of Slavic origin, so this mutation began to be called the «Slavic mutation». Our work presents a clinical case of Nijmegen breakage syndrome in a patient with bacterial destruction of the lungs. Increased sensitivity to ionizing radiation is a separate risk factor for patients with Nijmegen breakage syndrome. Due to frequent bacterial infections, children in this group are often subjected to multiple X-ray examinations, which can contribute to the emergence of malignant processes or the complicated course of already existing malignant processes, in particular leukemia and lymphoma.Conclusions. Nijmegen breakage syndrome is a rare genetic disease that requires a multidisciplinary approach for its diagnosis and treatment. The relevance of further research is due to the need for a deeper understanding of the pathogenesis of Nijmegen breakage syndrome and the development of new strategies for the comprehensive treatment of this pathological condition in children.The clinical case presented in our work demonstrates the importance of a comprehensive analysis and a thorough approach for the timely diagnosis and treatment of a rare disease, which may be an «incidental finding» in the practice of doctors of various specialties.