edit - My apologies for not previously citing my source for the graphics used in this post. Thanks to Steven M. Carr of Memorial University of Newfoundland, Canada for the remarkable work. The image can be seen at http://www.mun.ca/biology/scarr/FISH_chromosome_painting.html. Here is the copyright info from that page: "Text & image © 2008 by Steven M. Carr, after original by Genetix, with permission"
Here's my nutshell explanation of genetics for anyone who doesn't already know more than I do and is interested in Susan's medical issues, or in bizarre conditions in general. Keep in mind I'm not a science/medicine person by nature so it's all filtered through my liberal-arts mind.
We met with Dr. Dimitri, the geneticist, right after New Year's to talk about the results of some blood tests we ran on Susan in search of more information about the chromosomal abnormality that was diagnosed when she was an infant (Partial Trisomy 9 Mosaic). But alas, instead of learning more, now we know less: the blood test found no abnormal cells.
As you probably know, human DNA is passed from parent to child via chromosomes. A person has 23 pairs of chromosomes, which typically come in pairs: one copy of each chromosome is carried from each parent. When you have a blood test to test for genetic conditions, they extract chromosomes from blood cells, inject them with dye, and look at them under a microscope. They come out looking like this - a bunch of squiggly little lines:
Then the person running the test sorts all the squiggly lines into pairs from largest to smallest, and they come out looking like this:
And there you have your basic human chromosomal array. If the guy sorting them out finds an odd number of lines, that means there's something wrong. The degree to which something is wrong depends on which chromosome shows up an odd number of times. Since they all look a little different under the microscope, the test can show if you've got a third copy of one chromosome, a single copy of another, or some other weird variation. We fall into the weird variation category.
Just to clarify the vocabulary: if a person's cells have three copies of a single chromosome, instead of the usual two, that condition is called TRISOMY of that chromosome. Down Syndrome, the most common form of trisomy, occurs when somebody has three copies of chromosome 21. You can see from the array that 21 is the second-to-smallest of the chromosomes. The fact that the amount of genetic material that repeats is relatively small makes trisomy 21 a condition that causes some developmental and health issues, but doesn't otherwise disrupt the body's ability to function. When the bigger chromosomes start repeating, very bad things happen.
Now if the trisomy - the appearance of the extra chromosome - only occurs in some of the cells in a person's body, then the condition is called a MOSAIC trisomy. If a person has a mosaic condition, the trisomy could appear in any number between 0% and 99.9% of the body's cells. Generally, the higher percentage of trisomy cells a person has, the more severe the symptoms of trisomy are, but the percentage of affected cells is not necessarily consistent throughout the body. A person could have 100% of his skin cells carry trisomy 21, but still have 0% of his brain cells with trisomy. In that case, that person would have mosaic Down Syndrome, but might not show any symptoms at all. (That's not exactly true, since down syndrome effects other systems besides the brain, but it's just a metaphor.)
Separate from mosaicism, another variation on trisomy is a PARTIAL trisomy. That means that instead of having a full extra chromosome, you just have an extra piece of a chromosome. In Susan's case, she has an extra piece of chromosome 9. So while most people have two copies of chromosome 9, and someone with regular trisomy would have three copies of chromosome 9, Susan has something like 2.25 chromosome 9s in her cells. Like with mosaicism, the severity of symptoms of partial trisomy increase with the amount of extra genetic material that is present in the body. Complete trisomy 9 is one of the conditions labelled "not compatible with life," so if she had a full copy of 9 in all of her cells, Susan wouldn't be alive, period.
But not only does Susan have just a piece of an extra chromosome 9, making it a partial trisomy, that piece only occurs in some of her cells, making her a mosaic. This of course is so weird that nobody knows what it means exactly, other than that she's somewhere between normal and dead.
This much we've known since the first genetic tests were done just after she was born in 2003. Last year, we met a new geneticist, who recommended that we do additional testing to see what more we could learn about the extra piece of chromosome 9 that appears in some of her cells. Since chromosome 9 is a big one, it contains a lot of genetic information about a whole lot of different things. With the more advanced testing that is available now but was not a few years ago, we might be able to pinpoint which specific genes within the chromosome she has an extra copy of. This information would be helpful for diagnostic purposes, and give us a warning if there are specific things we need to watch for.
But instead of learning what extra genes she's carrying, they couldn't find any of the "trisomatic" cells at all. So, cool, that suggests that the percentage of her cells carrying the trisomy - i.e. the severity of her mosaicism - is probably fairly low. However, not so cool, we know absolutely nothing about the size or specifics of the partial trisomy. We could do another blood test, but there's no reason to think it would produce different cells this time. What we're probably going to do is get a skin sample and have them test those cells, because skin cells (according to the doctor) would probably have a more representative cross-section of what's happening throughout her body than blood. Taking a skin sample is no fun though, so we're going to wait until the next time she needs to have something done under general anesthesia and get it then.
Now, we also could just NOT do any more testing. It doesn't really change anything, there are no treatments for genetic anomalies, so it's really just data with no purposeful application. It is a lot like banging my head against a wall to learn more about something I can't do anything about. On the other hand, we DO want to know if she has increased risk of developing conditions in the future that are associated with chromosome 9. For example, chromosome 9 carries a gene associated with ovarian cancer. If we know she has an extra copy of that gene, we'll make she knows to watch her ovaries very closely throughout her life.
Honestly, it's probably mostly mental self-flagellation. I've spent a lot of time and effort getting my head around the way I think her issues arose, and an early genetic mutation is a big part of the story. If the story is proven wrong, then I'm back to not knowing much other than that my uterus screwed up big time and my kid has permanent problems because of it.
On the other hand, if her chromosomes are normal now, maybe there's something else that we should be treating but aren't because we've misdiagnosed the condition as genetic. She wasn't diagnosed with autism until she was five years old, even though she went through early intervention and has been in "the system" since she was newborn. The autism symptoms were just overshadowed by medical concerns, and when she was younger we could easily chalk it all up to prematurity. The older she gets, the less prematurity itself really explains.
So now we know she has symptoms of autism. We know from research that some autistic kids respond well to special diets, some to high-dose vitamin supplementation, etc. Do we need to be trying those things? Generally the docs always say "sure, it helps some kids, it's not harmful, give it a try... but keep in mind that she has an underlying genetic condition that is the root source of her problems." But now we have to wonder if maybe she DOESN'T have a genetic condition. What does that mean to treating her autism?
OK, I've spent an hour writing this, and I'm supposed to be studying for the freaking bar exam, which as most of you know, I failed the first time because I'm so distracted by playing the "medical mysteries" game. I'm going to go study some law. :)