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Chromosome Disorders in Pregnancy

The most significant biological factor in pregnancy loss are chromosome aberrations. Between 50 and 70% of all first trimester spontaneous abortions and at least 65 of stillborns are as a consequence of a chromosome aberration. Most of the time, there aberrations result in failure to thrive, malformations of various sorts and hydrops. They can also present on occasion with infertility and recurrent loss. Many times as one takes a family history, there may be other conceptions that had a chromosome aberration.

On occasion you will see that there are families with additional spontaneous abortions or infants born with various kinds of congenital malformations or birth defects. Basically in trying to discuss with you the focus of today’s presentation, I would like to talk to you about the inherent nature of different kinds of chromosome anomalies and characteristically we divide them into two groups, one, numerical changes in chromosomes as opposed to structural changes in chromosomes. Within the numerical group, there are two major subgroups or subtypes. There are times where there are gains or losses of single whole chromosomes.

When we begin to try to put this in perspective in terms of numbers and frequencies, it’s estimated that about 4% of all pregnancies carry a chromosome aberration. With data generated by the IVF programs, it’s estimated that between 15 and 30% of oocytes. contain a chromosome aberration and it depends on the nature, the way in which this oocyte was obtained, it’s morphologic appearance as to the actual number. You will read in the literature where there are chromosome aberrations.

If we start in the first trimester at 50 into the second and third at 10 and are down to 1 in 200, there is a pressure, if you will in some form or another that selects those that can proceed in complete gestation as opposed to those that fail. You will notice the breakdown again in the newborn period, characteristically again, about a third of the chromosome aberrations in the newborn involve the sex chromosomes about a quarter aneuploidy like trisomy 21, Downs syndrome, etc. and only about 8% represent unbalanced structural rearrangements in chromosomes. What do we then see when we discuss the patient population that presents which we consider a potentially high risk for a chromosome aberration, the infertile couple both male and female.

So let’s begin very quickly in the short time that is available to talk about the different kinds of numerical chromosome aberrations. We are going to talk about five separate and very quickly, different categories. Trisomy, the gain of a single whole chromosome, monosomy, the loss of a single chromosome, mosaic aneuploidy because it presents such a clinical dilemma particularly in prenatal diagnosis. A new area that is being developed in terms of it’s clinical consequences and significance, uniparental disomy which means that one pair of chromosomes originated from a single parent. In other words, the paired chromosome is maintained, but both of them came from one parent, and then very quickly about the clinical consequence.

Mosaic aneuploidy, by definition it means that you have two or more different chromosome constitutions in a single cell line or in a person, and this presents a clinical dilemma as how to counsel the patient appropriately. I have no smart answers for you, it’s a In the case of tetraploidy. Most tetraploid fetuses are lost in the first trimester. There have been some reports of diploid tetraploid mosaics which exhibit the characteristic features of a chromosome aberration, IUGR, malformations such as microcephaly and other major malformations, and it is this diploid tetraploid combination that probably allows these pregnancies to come to term. In the case of triploidy, it’s much more interesting. In the sense that if the extra set of chromosomes are paternal in origin and that occurs about 90% of the time, you get a very large placenta, a small fetus, partial hydatidiform mole.

Finally, I would like to talk about different kinds of chromosome rearrangement. Here I have to call on you to follow through with some additional reading. I can only summarize some basic features. Many of the terms that we use to describe chromosome aberrations are self defining. Deletion, loss of genetic material, duplication, gain of genetic material.

Inversion as the name suggests is that the gene order has been altered or changed, and a translocation means that the chromosomes broke and then exchange took place between the broken ends of chromosomes. There are a number of kinds of deletions, could be at the end, they can be interstitial, if the chromosome breaks, you can actually form a ring but the point I would like to make in terms of clinical consequences is, that characteristically, deletions lead to unbalanced chromosome complement and are associated with spontaneous abortion, stillbirth and birth defects. In terms of duplications, it appears as if the human body can tolerate duplications more than deletions and so they again can arise from a number of causes duplications.