WHEN ARE ANEUPLOID CELLS CLINICALLY SIGNIFICANT?

Abstract

Some workers suggest a causal relationship between multiple miscarriages or offspring with trisomy 21 and low frequency hyperdiploidy in the parents. Others consider low frequency aneuploidy of no clinical significance. We compared the frequency of aneuploid cells in five groups of subjects, karyotyped from 1978-83: 79 parents of trisomy 21 patients, 164 other 1st and 2nd degree relatives of Downs patients, 702 subjects with multiple miscarriage, 341 phenotypically and karyotypically normal control parents (e.g., parent of a dysmorphic child or member of a translocation family), and 1,165 others (e.g., chromosomally normal dysmorphic and retarded individual, etc.). In all, 47,595 cells were analyzed from 2,451 subjects. A cell was called hyperdiploid only if the extra chromosome(s) was recognizable and structurally normal.We found significant age and sex effects, but no other differences among the five groups of patients. Autosomal hypodiploidy (3.8% of cells) had no between group differences, but 45,X cells were age and sex associated: adult females .33%, adult males .17%, younger females .10%, and younger males .16%. Autosomal hyperdiploidy (.11% of cells) had no group, sex, or age differences. The frequency of X chromosome hyperdiploid cells was age and sex associated: adult females .26%, younger females .00%, adult males .04%, and younger males .00%. Females had a marked increase of X aneuploidy with age:age under 23 had .09% X0 and .00% +X cells,age 23 to 34 had .31% X0 and .21% +X cells, andage 34 to 50 had .64% X0 and .60% +X cells.In summary, the frequency of aneuploid cells was greater in females than males and was positively correlated with advancing age. Such cells were not more frequent in couples with multiple miscarriages or offspring with trisomy 21.