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.


METHODS
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.
New
Helen V
HV
Department of Haematology and Oncology, Great Ormond Street Children's Hospital, London, United Kingdom. helen.new@st-marysnhs.uk
Cale
C M
CM
Tischkowitz
M
M
Jones
A
A
Telfer
P
P
Veys
P
P
D'Andrea
A
A
Mathew
C G
CG
Hann
I
I
D018797:Cell Cycle Proteins / Q000235:genetics; D002675:Child, Preschool; D019457:Chromosome Breakage; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D003951:Diagnostic Errors; D005192:Family Health; D005199:Fanconi Anemia / Q000175:diagnosis*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics; D007223:Infant; D008223:Lymphoma / Q000175:diagnosis / Q000209:etiology; D009687:Nuclear Proteins / Q000235:genetics; D013577:Syndrome
D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins