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Autopsy findings for two patients with the Nijmegen breakage syndrome (NBS) are presented. This syndrome has the same type of immunologic and cytogenetic abnormalities as ataxia telangiectasia (AT). In NBS, however, microcephaly is found and progressive cerebellar ataxia and oculocutaneous telangiectasia are lacking. We demonstrate a clear neuropathologic difference between these two syndromes, as the diffuse cortical cerebellar degeneration characteristic of AT was absent in NBS. In the thymus the histologic picture was suggestive of simple dysplasia. Lymphoid tissues were slightly atrophic but otherwise structurally normal. In one of the two presented cases an extranodal diffuse large cell malignant non-Hodgkin lymphoma of B cell immunoblastic type was found in Waldeyer's ring, in the small and large intestines, and in the brain, whose sequelae had caused death. Six of the 19 patients known with certainty to have this syndrome have developed lymphoid malignancy, which indicates that these patients are prone to develop malignancies.

The light chain ratios and the concentrations of immunoglobulin G (IgG), IgA, and IgM were measured before, during, and after antileukemic therapy in 10 patients with common acute lymphoblastic leukemia. The concentrations of IgG, IgA, and IgM decreased substantially during treatment but recovered slowly after cessation of the therapy. The light chain ratios were not systematically affected, but at diagnosis the kappa/lambda ratios of total serum Igs, IgG, and in particular IgM were somewhat lower in the patient group compared with an age-matched reference group. It is concluded that, despite a decrease in serum Ig concentrations, virtually normal kappa/lambda ratios are preserved, indicating that kappa and lambda syntheses are affected to the same extent. These ratios remained normal for age during the recovery of the serum Ig concentrations; the features as described for the development of the light chain ratios in childhood were not observed.

We report the findings in the first 30 patients with the Nijmegen Breakage Syndrome (NBS). All had microcephaly from birth, short stature and a 'bird-like' face. Most of them suffered from recurrent respiratory tract infections. Intelligence was normal in half of the patients. Serum immunoglobulins were disturbed in 22/25 patients investigated (IgG deficiency, IgA deficiency, IgG2 and IgG4 deficiency) and T cell defects were found in 23/24 patients tested. The immunodeficiency appears to be more severe than in A-T. Chromosomal aberrations in cultured T lymphocytes occurred preferentially in chromosomes 7 and 14 and at the same breakpoints as in A-T. However, the percentage of chromosome 7 and/or 14 rearrangements was significantly higher in NBS patients than in A-T patients (p < 0.0005). Inv(7) was amongst the most frequently detected aberration in NBS cells as it is in A-T cells. Large clones of cells with rearrangements of chromosome 14 were rare in NBS. Of the first 19 reported patients eight have already developed a malignancy: seven a lymphoma and one a meningioma. It is noteworthy that both the tendency to express rearrangements of chromosomes 7 and 14 and the tendency to develop a malignancy is much higher in NBS than in A-T. Whether there is any causal relationship is as yet unknown.