Variegated aneuploidy related to premature centromere division (PCD) is expressed in vivo and is a cancer-prone disease

We present three patients with variegated aneuploidy and premature centrome re division (PCD), a rare chromosomal abnormality in humans. Comparison of these three and eight other patients with variegated aneuploidy related to PCD demonstrates a phenotype comprising most frequently microcephaly, CNS a nomalies (with cerebellar affection and migration defects), mental retardat ion, pre-and postnatal growth retardation, flat and broad nasal bridge, app arently low-set ears, eye and skin abnormalities, and ambiguous genitalia i n male patients. The occurrence of Wilms tumor in three patients, rhabdomyo sarcoma in two others and acute leukemia in a fifth characterizes this cond ition as a chromosome or genome instability disorder with a high risk of ma lignancy. FISH studies in uncultured blood and buccal smear cells demonstra te that the random aneuploidies are not limited to cultured cells, but also occur in vivo. (C) 2001 Wiley-Liss, Inc.