Role of chromosome aberrations in recurrent abortion: a study of 269 balanced translocations

We have studied a sample of 5,445 couples in which the woman was ascertained to have had two or more spontaneous abortions: 396 from our Cytogenetics Unit (present series) and 5,049 from the literature (literature series). In approximately 5% of these couples one of the members was a carrier of a balanced translocation, either reciprocal (2/3 of cases) or Robertsonian (1/3). In 1% of the couples there were other chromosome anomalies, mostly gonosomal aneuploidies or mosaicisms. A pericentric inversion of the heterochromatic region of chromosome 9 was present in 3% of the couples of the present series and in 1% of the literature series. The number of female carriers exceeded significantly that of males. The probability for one member of the couple to be a carrier increased with the number of abortions at the time of ascertainment, but it does not seem modified by the concomitant presence of term pregnancies. The analysis of the cytogenetic findings in 80 cases of Robertsonian and 156 cases of reciprocal translocations suggests that some chromosomes are preferentially involved, and that in reciprocal translocations the breakpoints are not distributed at random on the chromosome arms. There is an excess of breakpoints on chromosomes 6, 7, and 22 and a dearth on chromosome 12. This distribution is significantly different from that of a sample of reciprocal translocations ascertained for a malformed child. In both samples the breakpoints seem associated with fragile sites more frequently than expected by chance. An analysis of the potential and effective chromosome imbalance suggests that in subjects with unbalanced chromosomes survival is correlated with a minimum imbalance.