Nijmegen chromosomal breakage syndrome.

Nijmegen breakage syndrome was first described in 1981 by Weemaes CM as a new syndrome with chromosomal instability. The disease, which is characterized by microcephaly, delayed physical development, specific facial skeletal abnormalities, café-au-lait spots, and multiple breaks in chromosomes 7 and 14, was diagnosed in a 10-year-old boy. There is currently an international NBS registry that includes over 130 patients (unpublished data). Data on Russian patients with NBS have also been submitted to this registry. In 2000, the International NBS Study Group published data on the analysis of clinical and immunological abnormalities in 55 NBS patients; this report provides the most comprehensive description of the syndrome. In 1998, two research groups cloned the NBS gene, calling it HBS1. Over 60 patients with NBS were examined. The vast majority of them were homozygotes for a mutation of 5 nucleotides - 657 deLS (657-661 del ACAAA), which led to a shift in the reading frame and the appearance of a premature stop codon. These results confirmed the assumption that the mutation in NBS has a "founder effect".

Symptoms of Nijmegen Chromosome Breakdown Syndrome

Nijmegen chromosome breakage syndrome is common mainly among the population of central Europe, especially among Poles. In 2005, the registry included 55 people, 31 of whom were male and 24 were female. All patients had microcephaly and delayed physical development, half of them had normal intellectual development, while the rest had delayed intellectual development of varying degrees. All patients have characteristic abnormalities of the facial skeleton structure in the form of a sloping forehead, protruding middle part of the face, long nose, hypoplasia of the lower jaw, "Mongoloid" eye shape, epicanthus, large ears, and sparse hair. Some have telangiectasias on the scleral conjunctiva. Most patients have "café au lait" spots on their skin. The most common skeletal abnormalities are clinodactyly and syndactyly, less common are anal atresia or stenosis, ovarian dysgenesis, hydronephrosis, and hip dysplasia. Most patients suffer from recurrent and chronic bacterial infections of the respiratory tract, ENT organs, and urinary tract, and gastrointestinal tract infections occur less frequently. Various malignant neoplasms, primarily B-cell lymphomas, developed in 22 of 55 patients. Autoimmune diseases and hemocytopenia have also been described in patients with NBS. Various disorders of the lymphoid system are detected: hypo- or hyperplasia of the lymph nodes, hepatosplenomegaly.

Laboratory data

Laboratory examination revealed normal (in contrast to ataxia-telangiectasia) concentrations of alpha-fetoprotein. Various disorders were found in serum immunoglobulin concentrations: agammaglobulinemia (30% of cases), selective IgA deficiency, decreased IgG with high concentrations of IgA and IgM, deficiencies of IgG subclasses; impaired production of specific antibodies. When analyzing lymphocyte subpopulations, a decrease in the relative content of CD3+ and CD4+ cells with a normal level of CD8+ was most often detected. The proliferative response of lymphocytes to phytohemagglutinin is reduced.

The karyotype of all patients is normal, chromosomal aberrations, as in A-T, are represented mainly by rearrangement of chromosomes 7 and 14 in sites where immunoglobulin genes and the T-cell receptor are located. As a rule, lymphocytes and fibroblasts of patients with NBS grow poorly in cell culture, in addition, they differ from normal cells by increased sensitivity to ionizing radiation and chemical radiomimetics. Irradiation induces an increased number of chromosomal aberrations. In addition, cells of NB5 patients are not able to stop or slow down the S-phase of the cell cycle after exposure to high doses of radiation.

Treatment of chromosomal breakage syndrome Nijmegen

The main principles of therapy for patients with NBS are similar to those for CVID and hyper-IgM syndrome. Patients with NBS are prescribed replacement therapy with intravenous immunoglobulin and antimicrobial, antiviral, antifungal therapy. When treating malignant neoplasms in A-T and NBS, increased sensitivity to radiation and chemotherapy is taken into account.