Nijmegen Breakage Syndrome Health Article

Diagnosis

A diagnosis of NBS is suspected in children with small head size, slow growth at birth, characteristic facial features including a receding chin and prominent nose, recurrent infections, cancer (particularly B cell lymphoma), and borderline to moderate mental retardation. Prior to the discovery of the nibrin gene, diagnosis could only be confirmed by studying the levels of immune system proteins called immunoglobulins, looking for particular chromosomal changes involving chromosomes 7 and 14, and assessing radiation sensitivity in cells from patients.

Since the gene for NBS was discovered in 1998, it is now possible to look for a mutation in a patient's nibrin gene. All patients of Slavic origin and approximately 70% of the small number of patients in North America have had two copies of the common five DNA base mutation in the nibrin gene. Other North American patients have had at least one copy of another mutation unique to their family. If a mutation other than the common one is found, it is important to do further investigation to determine whether or not it causes disease, as non-disease causing changes have been reported in the nibrin gene.

Adults who are at risk for having children with NBS, such as siblings of patients, can have carrier testing to determine if they have one altered nibrin gene and are carriers for NBS. During pregnancy, the DNA of a fetus can be tested using cells obtained using the procedures called chorionic villi sampling (CVS), in which cells from the placenta are studied, or amniocentesis, in which skin cells from the amniotic fluid surrounding the baby are tested.

Treatment and management

There is no specific treatment for NBS, although folic acid (a vitamin B derivative) is recommended for prevention of chromosome breaks, since repair of these breaks is compromised in NBS. Similarly, vitamin E is recommended for prevention of further cell damage. For treatment of cancer, high doses of radiation must be avoided, since the damage inflicted on the cells could be fatal.

Prognosis

Patients with NBS have a decreased life span because of the tendency toward infection and cancer. Of the 55 patients in the NBS registry described in 2000, five had died from infections between infancy and eight years of age. Fourteen had died of cancer between the ages of two and 21 years of age. The remaining 36 living patients were between the ages of four and 30.

BOOKS

Wegner, Rolf-Dieter, et al. "Ataxia-Telangiectasia Variants (Nijmegen Breakage Syndrome)." In Primary Immunodeficiency Diseases: A Molecular and Genetic Approach, edited by Hans D. Ochs, et al. New York: Oxford University Press, 1999, pp. 324-334.

PERIODICALS

The International Nijmegen Breakage Syndrome Study Group. "Nijmegen Breakage Syndrome." Archives of Disease in Childhood 82 (2000): 400-406.

WEBSITES

Concannon, Patrick J., and Richard A. Gatti. "Nijmegen Breakage Syndrome." GeneClinics. University of Washington, Seattle. <http://www.geneclinics.org/profiles/nijmegen/index.html>. (March 31, 2001).

"Nijmegen Breakage Syndrome." OMIM—Online Mendelian Inheritance in Man. <http://www.ncbi.nlm.nih.gov/htbinpost/Omim/dispmim?251260>. (March 31, 2001).

"Nijmegen Breakage Syndrome." Virginia Mason Research Center. <http://www.vmresearch.org/nbsinfo.htm>. (March 31, 2001).

Toni I. Pollin, MS, CGC