Encyclopedia of Medical Immunology

Living Edition
| Editors: Ian MacKay, Noel R. Rose

Nijmegen Breakage Syndrome (NBS1)

  • Svetlana O. SharapovaEmail author
  • Larysa V. Kostyuchenko
Living reference work entry
DOI: https://doi.org/10.1007/978-1-4614-9209-2_161-1



Nijmegen breakage syndrome (NBS) is an autosomal-recessive chromosome instability disorder characterized by growth and developmental defects (growth retardation, severe and progressive microcephaly, a distinct facial appearance, lack of secondary sex characteristics in females, and frequent cryptorchism in males), immunodeficiency, high susceptibility to lymphoid malignancies, hypersensitivity to ionizing radiation, and aberrant cell-cycle checkpoint control (Varon et al. 2017; Seemanova et al. 2016). The disease is caused by mutations in the NBN gene (also abbreviated NBS, NBS1) and is located on chromosome 8q21 (GRCh38.p2: 89,933,336–89,984,733).


In 1981, Weemaes et al. from the University Hospital of Nijmegen, the Netherlands, first described the syndrome in two Dutch brothers with microcephaly, short stature, skin pigmentation abnormalities, mental...

This is a preview of subscription content, log in to check access.


  1. Deripapa E, Balashov D, Rodina Y, et al. Prospective study of a cohort of Russian Nijmegen breakage syndrome patients demonstrating predictive value of low kappa deleting recombination excision circle (KREC) numbers and beneficial effect of hematopoietic stem cell transplantation (HSCT). Front Immunol. 2017;8:807.CrossRefGoogle Scholar
  2. Gennery AR, Slatter MA, Bhattacharya A, et al. The clinical and biological overlap between Nijmegen breakage syndrome and Fanconi anemia. Clin Immunol. 2004;113(2):214–9.CrossRefGoogle Scholar
  3. Gennery AR, Slatter MA, Bhattacharya A, et al. Bone marrow transplantation for Nijmegan breakage syndrome. J Pediatr Hematol Oncol. 2005;27(4):239.CrossRefGoogle Scholar
  4. Nakanishi K, Taniguchi T, Ranganathan V, et al. Interaction of FANCD2 and NBS1 in the DNA damage response. Nat Cell Biol. 2002;4(12):913–20.CrossRefGoogle Scholar
  5. New HV, Cale CM, Tischkowitz M, et al. Nijmegen breakage syndrome diagnosed as Fanconi anaemia. Pediatr Blood Cancer. 2005;44(5):494–9.CrossRefGoogle Scholar
  6. Pastorczak A, Szczepanski T, Mlynarski W. Clinical course and therapeutic implications for lymphoid malignancies in Nijmegen breakage syndrome. Eur J Med Genet. 2016;59(3):126–32.CrossRefGoogle Scholar
  7. Resnick IB, Kondratenko I, Togoev O, et al. Nijmegen breakage syndrome: clinical characteristics and mutation analysis in eight unrelated Russian families. J Pediatr. 2002;140(3):355–61.CrossRefGoogle Scholar
  8. Seemanova E, Passarge D, Beneskova J, et al. Familial microcephaly with normal intelligence, immunodeficiency, and risk for lymphoreticular malignancies: a new autosomal recessive disorder. Am J Med Genet. 1985;20(4):639–48.CrossRefGoogle Scholar
  9. Seemanová E, Sperling K, Neitzel H, et al. Nijmegen breakage syndrome (NBS) with neurological abnormalities and without chromosomal instability. J Med Genet. 2006;43(3):218–24.CrossRefGoogle Scholar
  10. Seemanova E, Varon R, Vejvalka J, et al. The Slavic NBN founder mutation: a role for reproductive fitness? PLoS One. 2016;11(12):e0167984.CrossRefGoogle Scholar
  11. Slack J, Albert MH, Balashov D, et al. Outcome of hematopoietic cell transplantation for DNA double-strand break repair disorders. J Allergy Clin Immunol. 2018;141(1):322–328.e10.CrossRefGoogle Scholar
  12. Varon R, Vissinga C, Platzer M, et al. Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome. Cell. 1998;93(3):467–76.CrossRefGoogle Scholar
  13. Varon R, Seemanova E, Chrzanowska K, et al. Clinical ascertainment of Nijmegen breakage syndrome (NBS) and prevalence of the major mutation, 657del5, in three Slav populations. Eur J Hum Genet. 2000;8:900–2.CrossRefGoogle Scholar
  14. Varon R, Dutrannoy V, Weikert G, et al. Mild Nijmegen breakage syndrome phenotype due to alternative splicing. Hum Mol Genet. 2006;15(5):679–89.CrossRefGoogle Scholar
  15. Varon R, Demuth I, Chrzanowska KH. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2018. 999 May 17 [updated 2017 Feb 2].Google Scholar
  16. Weemaes CM, Hustinx TW, Scheres JM, et al. A new chromosomal instability disorder: the Nijmegen breakage syndrome. Acta Paediatr Scand. 1981; 70(4):557–64.CrossRefGoogle Scholar
  17. Wolska-Kuśnierz B, Gregorek H, Chrzanowska K, et al. Nijmegen breakage syndrome: clinical and immunological features, long-term outcome and treatment options – a retrospective analysis. J Clin Immunol. 2015;35(6):538–49.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Svetlana O. Sharapova
    • 1
    Email author
  • Larysa V. Kostyuchenko
    • 2
  1. 1.Research DepartmentBelarusian Research Center for Pediatric Oncology, Hematology and ImmunologyMinskBelarus
  2. 2.Department of Clinical Immunology and AllergologyDanylo Halytsky Lviv National Medical University, West-Ukrainian Specialized Children’s Medical CenterLvivUkraine

Section editors and affiliations

  • Jolan Walter
    • 1
  1. 1.USF HealthTampaUSA