Nijmegen breakage syndrom (NBS)

Abstract

Nijmegen breakage syndrome (NBS) is an autosomal recessive syndrome of chromosomal instability. Clinical features are prenatal as well as postnatal growth retardation, severe congenital microcephaly, humoral and cellular immunodeficiency, respiratory infections, predisposition to bronchiectasia, high risk for lymphoreticular malignancy. Characteristic facies with low forehead, prominent midface, retromicrognathia, large auricles is apparent from the age of 3 years. Laboratory findings include low immunoglobulins, chromosomal breaks with typical rearrangement of chromosomes 7 and/or 14 and cellular hyperradiosensitivity and radioresistant DNA synthesis. The gene, responsible for NBS called NBS1, was localised in 1997 on 8q21 and cloned in 1998. Six different mutations were detected so far in NBS1 gene, mutation 657del5 is characteristic for Slavonic populations. Detection of the NBS1 mutations allows an exact postnatal and prenatal diagnosis. Nibrin, the protein product of NBS1 gene protects cell and chromosomes from deleterious effects of ionising radiation. Hyperradiosensitivity of 657del5 homozygotes has important implications for clinical prognosis and for treatment after the patients develop malignancy.