Ataxia-pancytopenia: syndrome of cerebellar ataxia, hypoplastic anemia, monosomy 7, and acute myelogenous leukemia

Abstract

In a family with ataxia and pancytopenia, the proband had cerebellar ataxia, developed hypoplastic anemia at age 3 years, and died of acute myelomonocytic leukemia at age 7. Serial cytogenetic studies of the proband's hypoplastic bone marrow over a 25-month period revealed progressive expansion of a clone of cells with C(6 - 12 + X) monosomy from 33% to 94% of metaphases. The missing chromosome by banding was deduced to be No.7. No increased sensitivity of the patient's cells was found in response to ultraviolet or ionizing radiation or to mitomycin C. Cerebellar atrophy was confirmed at autopsy. Family studies revealed cerebellar ataxia in the proband's father and all four siblings. Two brothers, including one with C-monosomy, died with hypoplastic anemia and another brother died with acute myelocytic leukemia. The only surviving sibling is a 19-year-old sister who has unexplained anemia, decreased mitotic activity in bone marrow, and slow progressive cerebellar ataxia. The name ataxia-pancytopenia syndrome is proposed to encourage study of additional patients with this disorder, which predisposes to pancytopenia and acute leukemia.