Nijmegen breakage syndrome (NBS) is a rare autosomal recessive[2] congenital disorder causing chromosomal instability, probably as a result of a defect in the double Holliday junction DNA repair mechanism and/or the synthesis dependent strand annealing mechanism for repairing double strand breaks in DNA (see Homologous recombination).

It is characterized by microcephaly, a distinct facial appearance, short stature, immunodeficiency, radiation sensitivity and a strong predisposition to lymphoid malignancy.

Unsurprisingly, many of the features are similar to ataxia telangiectasia (AT) and this syndrome was sometimes termed AT-variant 1, as the protein mutated in AT, ATM, interacts with the MRE11/RAD50/NBS1 (MRN) complex.

[11] These individuals appear to be primarily defective in homologous recombination, a process that accurately repairs double-strand breaks, both in somatic cells and during meiosis.

In the treatment of malignancies, radiation therapy, alkylating antineoplastic agents, and epipodophyllotoxins are not used, and methotrexate can be used only with caution; the dose should be limited.