Syndrome of chromosomal breakages of Nijmegen

The Nijmegen breakage syndrome was first described in 1981. Weemaes CM as a new syndrome with chromosomal instability. The disease manifested by microcephaly, lagging behind the physical development, specific disorders of the facial skeleton, skin spots of the color "coffee with milk" and multiple breakdowns of 7 and 14 chromosomes was revealed in a 10-year-old boy. Currently, there is an international NBS register, which includes more than 130 patients (unpublished data). Information about Russian patients with NBS is also sent to this register. In 2000, the International Group for the Study of NBS published data on the analysis of clinical and immunological disorders in 55 NBS balloons, this report gives the most complete characterization of the syndrome. In 1998, two groups of researchers cloned the NBS gene, called HBS1. More than 60 patients with N BS were examined. The overwhelming majority of them turned out to be homozygotes for a mutation of 5 nucleotides - 657 deLS (657-661 del ASAAA), 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 with NBS has a "founder effect".

Symptoms of the syndrom of chromosomal breakages Nijmegen

The syndrome of chromosomal breakdowns of Nijmegen is prevalent mainly among the population of central Europe, especially among the Poles. In 2005, the register included 55 people, 31 of them men, and 24 women. All patients had microcephaly and a delay in physical development, half of the intellectual development is normal, others have a delay in intellectual development of varying degrees. In all patients, characteristic disorders of the structure of the facial skeleton in the form of a beveled forehead, protruding middle part of the face, a long nose, hypoplasia of the lower jaw, a "Mongoloid" cut of the eyes, epicanth, large ears, rare hair. Some have telangiectasias on the scleral conjunctiva. Most patients have spots of "coffee with milk" color on the skin. The most common disorders of the skeleton are clinodactyly and syndactyly, less frequent atresia or stenosis of the anus, ovarian dysgenesis, hydronephrosis, hip dysplasia. The majority of patients suffer from recurrent and chronic bacterial infections of the respiratory tract, ENT organs, and the urinary system, and rarely there are infections of the gastrointestinal tract. In 22 of 55 patients, various malignant neoplasms, mainly B-cell lymphomas, developed. Patients with NBS also described the development of autoimmune diseases, hemocytopenia. From the side of the lymphoid system, various abnormalities are detected: hypo- or hyperplasia of the lymph nodes, hepatosplenomegaly.

Laboratory data

During laboratory examination, normal concentrations of alpha-fetoprotein were detected (in contrast to ataxia-telangiectasia). Various abnormalities were detected from the serum immunoglobulin concentrations: agammaglobulinemia (30% of cases), selective IgA deficiency, IgG decrease at high concentrations of IgA and IgM, deficiencies of subclasses of IgG; the development of specific antibodies is impaired. When analyzing the subpopulations of lymphocytes, the decrease in the relative content of CD3 + and CD4 + cells at the normal CD8 + level was most often detected. Proliferative response of lymphocytes to phytohemagglutinin is reduced.

Karyotype in all patients is normal, chromosomal aberrations, as in the case of AT, are mainly represented by the re-arranging of chromosomes 7 and 14 in sites where the immunoglobulin and T-cell receptor genes are located. As a rule, the lymphocytes and fibroblasts of patients with NBS do not grow well in the cell culture, in addition, they differ from normal hypersensitivity to ionizing radiation and chemical radiomimetics. Irradiation induces an increased number of chromosomal aberrations. In addition, cells of patients with NB5 are unable to stop or slow the S-phase of the cell cycle after exposure to high doses of radiation.

Treatment of the syndrome of chromosomal breakdowns Nijmegen

The basic principles of therapy for patients with NBS are similar to those in OVIN and hyper-IgM syndrome. Patients with NBS are prescribed intravenous immunoglobulin replacement therapy and antimicrobial, antiviral, antifungal therapy. At treatment of malignant neoplasms at АТ and NBS the raised sensitivity to radiation and a chemotherapy is considered.