Balanced complex chromosome rearrangements: reproductive aspects. A review

Abstract

This review examines the reproductive consequences for carriers of a balanced complex chromosome rearrangement (CCR). It is based on an analysis of CCRs in 103 adults referred for reproductive problems, including male infertility. The main focus is on reproductive risks based on data from 84 CCRs. Carriers of balanced CCRs have a high risk of an abortion and/or a chromosomally unbalanced child. I have identified roughly four different types of CCRs (I-IV); most (44%) belong to Type I with a simple 3-way or 4-way exchange of segments and risk factors similar to those for reciprocal translocations. There were only three CCRs (4%) of type II, which involve an inversion. Type III CCRs (21%) involve one or more insertions with ∼35% risk of a child with a duplication or a deletion of the inserted segment. Type IV CCRs (31%) involve a "middle segment" in a derivative chromosome with segments from at least three chromosomes. In ∼35% of these CCRs, recombination occurs in this segment, which can produce imbalance but in many cases it changes a CCR into a simpler balanced rearrangement in the next generation. Balanced CCRs, which have been often considered together in one group, can now be split into four types, each with a risk of a different type of imbalance. This analysis provides a better understanding of the reproductive consequences for carriers of balanced CCRs and should be useful in prenatal diagnosis and genetic counseling.