ABSTRACT
Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder characterized by microcephaly, dysmorphic facial features, mild growth retardation, mild-to-moderate intellectual disability, premature ovarian insufficiency, cellular and humoral immunodeficiency with recurrent sinopulmonary infections, radiosensitivity, and predisposition to lymphoid malignancies at early age. NBS is a rare disease with an estimated incidence of 1 per 100,000 live births in North and South America, Morocco, and New Zealand. Diagnosis of NBS is based on observation of characteristic clinical manifestations, chromosomal instability, increased cellular sensitivity to ionizing radiation in vitro, combined cellular and humoral immunodeficiency, mutations in both alleles of the NBN gene, and complete absence of full length nibrin. NBS patients treated for one cancer may have increased risk of developing different consecutive malignant disease. The underlying mechanism of NBS relates to homozygous or compound heterozygous mutations in the NBS gene encoding a protein that forms a trimeric complex with MRE11 and RAD50 for repairing DNA DSB after exposure to ionizing radiation.
