A Short Lesson in Genetics or What the Hell is Wrong with Me…

I probably should have done this months ago since it’s really essential to understanding what my major malfunction is….Hang in there, it’s technical…

Under normal circumstances, humans have 46 chromosomes in each of the cells that make up their bodies. The complement of 46 chromosomes is composed of 22 pairs of ‘autosomes’ and 1 pair of sex (either XX = female, or XY = male) chromosomes – half of the total complement being inherited from each parent. Individual chromosomes are quite distinct in their appearance and most have long and short ‘arms’ that are connected by a structure called the centromere. When cells replicate to make another cell, they first duplicate their chromosomes and centromeres. The centromeres then connect to the structures in the cell that help separate these duplicated chromosomes from each other so that each new cell which results gets exactly the same chromosomal complement that was present in the ‘mother’ cell. This event is called mitosis.

To produce gametes (ova and sperm), a slightly different process is involved. Following duplication of the chromosomes, the overall complement of chromosomes delivered to each gamete mustbe reduced to half (23) that found in other cells in the body. This is two-step process called meiosis in which the centromeres also play a key role. During meiosis, the individual chromosomes (that were inherited from each of your parents) segregate more or less randomly into the resulting gametes, providing the great variability seen in our offspring.

Five of our chromosomes (13, 14, 15, 21 and 22) have ‘short arms’ that are very small and which contain no essential genetic material. These 5 chromosomes are called acrocentric chromosomes, or ‘acrosomes.’ Acrosomes have a tendency to fuse at the centromeres with other acrosomes, thus producing a ‘single’ larger chromosome made up of the ‘long arms’ of the chromosomes of origin, connected by a single centromere. When this occurs it is known as a ‘Robertsonian translocation.’ If no essential genetic material is lost (or gained) in the process, the individual with such a chromosome is said to have a ‘balanced’ translocation and appears ‘normal’ although they now have only 45, rather than 46, chromosomes in each cell.  That’s me.  I have one 13, one 14 and one 13/14 which are fused.  I’m not lacking any genetic material since the short arms don’t contain anything essential.  For what it’s worth, both boys were just like me.  We had to have an amnio done after the ablation and that’s when this was discovered.  The cell indicated that Baby B was exactly like me and therefore, Baby A, since they were identical twins, would have been too.  The translocation is not why they died.

Robertsonian translocations can occur between any of the acrosomes although this is not entirely random and the most common forms of these occur between chromosomes 13 and 14 (75%). Individuals with Robertsonian translocations can have these as the result of a spontaneous event occurring during the meiosis (in either parent) that produced the egg or sperm from which they were made, shortly after conception (called “de novo”), or from the inheritance of the same from one of their parents.  I don’t know which one I have.  I have no siblings so it’s hard to know if mine is “de novo” or inherited.  Doesn’t really matter for that reason, no one else, aside from my children will need to know this because there is no one else of child bearing age.

Robertsonian translocations are present in approximately 1/1,000 newborns. Individuals with balanced translocations are usually healthy and often unaware of their condition, especially if there is no prior family history that has led to the diagnosis, and often their chromosomal ‘abnormality’ will not be discovered until they have difficulty having children. The problem arises when individuals with Robertsonian translocations try to make gametes.  My gametes can have one of six scenerios:

1) One free copy of chromosome (chr) 13 and one free copy of chr 14.

2) The translocation (chr 13;14) chromosome alone (which contains one copy of chr 13 fused with one copy of chr 14).

3) Chr 13;14 + one free copy of chr 13 (essentially, a gamete with TWO copies of chr 13 rather than just one).

4) One free copy of chr 13 (and NO copy of chr 14).

5) Chr 13;14 + one free copy of chr 14 (TWO copies of chr 14 rather than just one).

6) One free copy of chr 14 (and NO copy of chr 13).

Obviously, 3 through 6 are gametes that have the incorrect number of chromosomes (either too little or too much genetic material). When these gametes get together with the, presumably, ‘normal’ gametes from Tim (which contain one free copy of chromosome 13 and 14), the following possibilities result (in the same order as above):

1) Two free copies of chr 13 + two free copies of chr 14 = NORMAL

2) Chr 13;14 + one free copy of chr 13 + one free copy of chr 14 = translocation ‘carrier’ (just like me) with NORMAL TOTAL amount of genetic material

3) Chr 13:14 + TWO free copies (one EXTRA from Me and one from Hubby) of chr 13 + one free copy (from Hubby) chr 14 = TRISOMY 13

4) Two free copies chr 13 (one from Me and one from Hubby) + ONE free copy of chr 14 (NONE from Me and one from Hubby) = MONOSOMY 14

5) Chr 13:14 + one free copy of chr 13 (from Tim) + TWO free copies (one EXTRA from Me and one from Hubby) chr 14 = TRISOMY 14

6) ONE free copy chr 13 (NONE from Me and one from Tim) + two free copies of chr 14 (one from Me and one from Hubby) = MONOSOMY 13.

Mathematically, I only have a 2 in 6 (33.3%) chanceof having a baby that has the right TOTAL amount of genetic material; one of these will be entirely chromosomally normal and the other will be a translocation ‘carrier’ just like me.  Two-thirdsof my babies are at risk for being chromosomally ABNORMAL.  This is how the geneticist explained it to me.  However, things are not quite that simple. Indeed, my actual risk for having a living baby with a chromosomal abnormality is much lower than this. The monosomy 13 and 14 embryos will not be successful at all (this is my 8-9 week miscarriages) and the trisomy 14 embryos also have very little chance of surviving much of the first trimester. Most trisomy 13 embryos will also be lost early in first trimester (this is my 5-6 week miscarriages) and the few that survive will have only a small chance of surviving the pregnancy and even a smaller chance of living more than a few hours or days after birth (we would know around 13 weeks if we had a Trisomy 13 fetus). These babies all have severe congenital malformations and if they manage to survive birth and the neonatal period, profound metabolic disturbances, and mental retardation. UNC has NEVER seen a living Trisomy 13 baby at birth.  I am aware that they do exist.

Some doctors argue that the ‘selective forces’ are so strong against these chromosomally abnormal conceptuses that at least two-thirds of pregnancies in which a pregnancy is actually confirmed will be chromosomally normal and the chances of actually DELIVERING a chromosomally abnormal baby are probably only about 1%!  That’s making the assumption that I don’t get a positive pregnancy test.  This is based on the argument that the pregnancy will end before I even know it’s happened.  That’s not the case with me.  I’ve been pregnant 6 times in 18 months.  I don’t need EPT to tell me when I’m pregnant.  I’m the Goddamn bloodhound of knowing when I am pregnant. 

So if you take out the instances when the pregnancy isn’t even “confirmed,” it appears that the overall risk of miscarriage is about 25% and this is the number doctors like to toss about. 

Makes me feel warm and squishy to think it’s only 25% but really, rational me knows that’s not the case.

Anymore questions, ask me, I’ll tell you…