Clinical presentation and mutation identification in the NBS1 gene in a boy with Nijmegen breakage syndrome

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder which belongs to the group of inherited chromosomal instability syndromes. The clinical characteristics include severe microcephaly, a dysmorphic facies, and immunodeficiency with predisposition to malignancies. While the cellular characteristics of ataxia teleangiectasia (AT) and NBS are similar, the clinical findings are quite distinct. NBS patients show characteristic microcephaly, which is rare in association with AT and they do not develop ataxia and teleangiectasia. Recently, the gene mutated in NBS has been identified. Here we report a 5-year-old Bosnian boy with severe microcephaly. Because of multiple structural aberrations involving chromosomes 7 and 14 typical for AT (MIM 208900) and NBS (MIM 251260), AT was diagnosed. We suggested the diagnosis of NBS because of the boy's remarkable microcephaly, his facial appearance, and the absence of ataxia and teleangiectasia. DNA analysis was performed and revealed that the boy is homozygous for the major mutation (657de15) in the NBS1 gene. This finding confirms the diagnosis of NBS in our patient and offers the possibility to perform a most reliable prenatal diagnosis in a further pregnancy.