March is Trisomy Awareness month and so I decided now is as good a time as any for me to finally tackle another of my informative posts. This one about Chromosomes and Trisomy. I have put off doing this post for several months because, well frankly, this genetics stuff is complicated and I'm not sure I entirely understand it. But here is my best shot at explaining about chromosomes and what makes Ellie unique.
Chromosomes are found in the nucleus of all body cells and carry the genetic characteristics of each individual. Every person has 22 pairs of human chromosomes with an unequal 23rd pair (XY for males, XX for females).
People with a trisomy have an extra chromosome added to one of the normal pairs. The most common trisomy is Trisomy 21 (Down Syndrome). The presence of an extra chromosome, such as in Trisomy 21, results in a characteristic pattern of features, birth defects, and medical problems that is recognized as a syndrome.
Ellie's trisomy does not effect the entire 4th chromosome. Each chromosome has a short "p" arm and a longer "q" arm. Ellie has a duplication of the short p arm of chromosome 4, resulting in the diagnosis of Trisomy 4p. Remember that there are only somewhere around 100 documented cases of Trisomy 4p world wide (that number is a bit outdated and I think it is being diagnosed more and more frequently as genetic testing is becoming more widely available), but this next part is part of what truly makes Ellie one of a kind. Not all 4p duplications are the same. Some affected people have smaller, partial duplications for example only 4p16.3-4p16.1 is duplicated or 4p16.3-4p15.1 (see diagram below). Generally, the smaller the duplication the less severely affected the individual. Ellie is one of the few who has a complete duplication (4p16.3-4p11). This means it is likely that she will be more severely affected.
But that isn't where the uniqueness ends. Each person further varies in where their duplication is translocated (where it is attached). Some remain attached to chromosome 4, others are attached to a different chromosome. Some are inverted (the duplication is in a backwards sequence) and some involve deletions (a chromosome has missing material that the duplication has taken of the place of). In Ellie's case, her 4p duplication is translocated onto chromosome 15 without an inversion or any deletions. Below I have taken a typical female karotype and colored the duplicated 4p arm red and colored an additional red 4p arm to show where Ellie's duplication is located.
After comparing specifics of everyone's duplications within our 4p group I have yet to hear of any two children who have the same duplication. That is why there is so much variability in presentation between all of them. Each of these kiddos is literally one of a kind. Pretty amazing, if you ask me.
So why? What caused this change in Ellie's chromosomes? Believe me, I have spent a lot of sleepless nights thinking about this. Wondering what I did or didn't do during those 9 months when it was my sole responsibility to give Ellie everything she needed to grow and develop. Was it because I ate too many chicken strips and fries and not enough vegetables? Was it because I ate deli meat or because I stood in front of the microwave while it was going? Was it because I trained for and ran Ragnar when I was 13 weeks pregnant? Was it because I didn't know I was pregnant for several months and wasn't taking prenatal vitamins? Was it because I was working too much and sleeping too little? Was it because this was my fourth pregnancy and I just got a little careless and didn't worry about all the little things? It took me a while to let myself off the hook, but it really was not because of anything I or anyone else did. This was something that was built into who Ellie is from the very beginning and there is absolutely nothing I could have done to prevent it from happening.
In 75% of cases one of the parents has a balanced translocation, which is an inherited rearrangement of chromosomes where some of the chromosomal material is out of order, but it is all still there, so it doesn't cause problems. (For more information on balanced translocations go here) The other 25% are referred to as de novo, meaning it is a random mutation. Scott and I have not been tested since it is a very expensive test and the results really only matter if we were planning on having more children, which we are not. The only other implication of one of us having a balanced translocation is that any of our three older children could also have a balanced translocation. We will let them each decide when they get older if they want to be tested. I am highly suspicious that Ellie's is de novo seeing as our history doesn't really fit the mold of families that have balanced translocations in them. Both Scott and I come from large families that have no history of abnormalities or problems. We never had a hard time getting pregnant, never had any miscarriages, and had three typical children before having Ellie. I could be wrong, but that is my gut instinct.
Well, there you have it. Was that clear as mud?
