Nijmegen breakage syndrome is a rare autosomal recessive condition, which belongs to the DNA repair disorders. The hallmarks of Nijmegen breakage syndrome are microcephaly, a typical facial appearance, growth retardation, immunodeficiency accompanied by recurrent infections, chromosomal instability, X-ray hypersensitivity, and predisposition to malignancy. Additional features include skin abnormalities, particularly café-au-lait spots and vitiligo, and congenital malformations, particularly clinodactyly and syndactyly. Psychomotor development is usually normal or only mildly to moderately retarded despite severe microcephaly. About three quarters of the Nijmegen breakage syndrome patients are microcephalic at birth and the remainders become microcephalic within the first year of life. Severe microcephaly at birth may be associated with normal mental development and counterwise. Life expectancy is reduced because of their tendency to develop malignancies at a relatively young age and sometimes fatal infections.

The gene responsible for Nijmegen breakage syndrome, NBS1, is located on chromosome 8q21. The NBS1 gene consists of 16 exons and spans approximately 50 kb of DNA. The gene encodes two transcripts of 4.4 and 2.4 kb that are expressed in all tissues examined and differ only in their site of polyadenylation. Both transcripts contain a single open reading frame coding for a protein of 754 amino acids with a predicted molecular weight of 85kd, called NIBRIN. All disease-causing alleles of the NBS1 gene identified to date are null alleles. The 657del5 mutation predominates, accounting for greater than 90% of all mutant alleles in Nijmegen breakage syndrome. All known Nijmegen breakage syndrome mutations are predicted to result in truncation of the NIBRIN protein.