Unexpected encounters in cytogenetics: repeated abortions and parental sex chromosome mosaicism may indicate risk of nondisjunction.

Unexpected encounters occur in cytogenetics. In 1964 a survey reported 60 families with a trisomy 13 or 18 child seen for dermatoglyphic investigation of the normal relatives. We found "quite incidentally" that four of the 60 families contained another person with a different chromosome abnormality: Down syndrome. The report [1] was entitled "The nonrandomness of chromosomal abnormalities." The dermatoglyphic survey was never published. We recently saw a couple who had lost a Down syndrome child. The couple wished to know how this had happened, so chromosome studies were done. We found that the mother had a different chromosome abnormality: 46,XX/47,XXX mosaictsm. We saw another couple with a trisomy 21 child. The mother conceived anew and had a spontaneous abortion early in pregnancy. The abortion had a different chromosome abnormality: 45,X. You lodge an objection. These are anecdotes, you say, unexpected and tantalizing, but, nonetheless, just anecdotes. You want numbers. To ascertain translocations, we are currently studying chromosomes from couples with two or more spontaneous abortions, excluding couples with an anomalous child. In the first 50 couples, we found three translocations and one inversion. Unexpectedly, we stumbled upon a different chromosome abnormality in five phenotypically normal individuals: sex chromosome mosaicism. In this issue, Michels, Medrano, Venne, and Riccardi [2] report chromosome studies in 440 individuals (including 200 couples) with two or more spontaneous abortions. Their population sample is the largest, I believe, to be reported, and it confirms clearly that "two or more spontaneous abortions constitute a reasonable criterion" for the cytogenetic study of couples with multiple miscarriages. This is a complex and confusing area of research. Variables are numerous: the timing of the spontaneous abortions, the exact number of miscarriages, the inclusion or exclusion of couples with normal children and anomalous offspring, and, what is almost impossible to measure, the extent of medical evaluation prior to chromosome studies. Because of all of these variables, it is hard to pool data meaningfully from the literature. Let's summarize what we know about repeated-abortion couples. Translocations are significantly more frequent in these couples than in the general population [3, 4]. Inversions may be more frequent, too; logic suggests this is true. By contrast, chromosome variants (polymorphisms and heteromorphisms) have not been conclusively proven to be associated with repeated abortions.