Nijmegen breakage syndrome diagnosed as Fanconi anaemia

BACKGROUND: Fanconi anaemia (FA) and Nijmegen breakage syndrome (NBS) are rare chromosomal instability disorders with overlapping clinical features. It has recently been shown that, like FA, NBS is also associated with increased chromosomal sensitivity to DNA cross-linking agents. PROCEDURE: We report a family that was initially diagnosed with FA on the basis of increased sensitivity to DNA cross-linking agents. They were atypical in that there were associated severe infection problems. In view of these features we performed immune function studies together with molecular analysis of the FA genes and subsequently the NBS1 gene. RESULTS: Two children in the kindred have died, one from sepsis, and the other with a plasma cell malignancy. A third child underwent bone marrow transplantation because of recurrent infections. All affected members had severe immunological abnormalities. The genetic defect was shown to be a novel mutation in the NBS1 gene, so the diagnosis was revised to that of NBS. CONCLUSIONS: This family illustrates the importance of awareness of the lack of specificity of DNA cross-linking agent tests for FA, particularly in situations where the clinical features are atypical. In addition, one of the cases represents the first use of bone marrow transplantation for NBS that we are aware of; this treatment may have a future role for other patients with the syndrome.