A family with acute leukemia, hypoplastic anemia and cerebellar ataxia. Association with bone marrow C-monosomy

The eldest brother in a sibship of five children died of acute myelogenous leukemia at 10 years of age. The second and third eldest brothers died of hypoplastic anemia at ages five and nine years, respectively. A surviving 6 year old brother, the proband of the study, has abnormalities that suggest a preleukemic state: mild pancytopenia, platelet dysfunction, immunodeficiency, and bone marrow hypoplasia with approximately 18 per cent blast forms. His 17 year old sister has a mild normochromic normocytic anemia. Cytogenetic studies revealed C-group monosomy in the bone marrows of the proband and the third brother (45, XY, -C); banding studies demonstrated that a No. 8 chromosome was missing in the proband (45, XY, -8). At least four of the siblings and their father had cerebellar ataxia, and evidence of a small cerebellum at autopsy examination or by computerized axial tomography. The disorder in this family has major features of two autosomal recessive preleukemic diseases, ataxia-telangiectasia and Fanconi's anemia. However, these and other inherited conditions were excluded by clinical or laboratory criteria, and no environmental causes of the familial disorder were found. The constellation of abnormalities in the family may constitute a new genetic syndrome.