Nijmegen Breakage Syndrome (NBN)
Nijmegen breakage syndrome is an autosomal recessive disorder caused by pathogenic variants in the gene NBN. While it is found in populations around the world, Caucasian individuals are more likely than individuals of other ethnicities to be carriers. Individuals with two pathogenic NBN variants have increased levels of chromosome instability, resulting in short stature, progressive intellectual disability, and recurrent lung, ear, sinus and gastrointestinal infections. Patients also have a characteristic facial appearance and a very high risk of cancer; about 40% of patients will have developed a malignancy before the age of 20. As a result, the life expectancy of patients with Nijmegen breakage syndrome is shortened. Some patients may live into adulthood. Several specific variants have been associated with a mild phenotype, but the phenotype is severe in most patients regardless of the genotype.
For information about carrier frequency and residual risk, please see the residual risk table.