Nijmegen Breakage Syndrome-Like Disorder

A number sign (#) is used with this entry because of evidence that this phenotype results from mutation in the RAD50 gene (604040).

Clinical Features

Barbi et al. (1991) reported a microcephalic, growth-retarded newborn girl without major anomalies who had chromosome instability in lymphocytes and fibroblasts. Frequent involvement of bands 7p13, 7q34, 14q11, and 14q32 suggested the diagnosis of ataxia-telangiectasia (AT; 208900). She had radioresistant DNA synthesis in fibroblasts and radiation hypersensitivity of short-term lymphocyte cultures. Follow-up at 4 years of age showed largely normal development and no signs of telangiectasia, ataxia, or immunodeficiency. Serum AFP levels were elevated at age 5 months, but declined to normal by age 2 years. Fibroblasts showed radioresistant DNA synthesis typical of AT or the Nijmegen breakage syndrome (251260).

Waltes et al. (2009) reported further phenotyping of this female, who was 23 years of age at that time. She had mild to moderate retardation of psychomotor development, mild spasticity, and very modestly impaired sensomotor coordination manifesting as a slight and nonprogressive ataxia. Physical exam showed a bird-like face and height, weight, and head circumference well below the third percentile. Puberty and secondary sexual characteristics appeared normal. She had areas of hyper- and hypopigmentation diffusely and had severe hyperopia. She had no history of infections, had normal immunoglobulin subclasses, and no evidence of malignancy. By the age of 23 years, she was living in her own apartment in an assisted living facility.

Molecular Genetics

In a patient with a Nijmegen breakage syndrome-like disorder (NBSLD), Waltes et al. (2009) identified compound heterozygosity mutations in the RAD50 gene, a maternally inherited nonsense mutation (604040.0001) and a paternally inherited point mutation that resulted in extension of the protein by 66 amino acids (604040.0002).