Huntington Disease is going to serve as our prototype...
for more discussion into the nuances of what we're here for today because it is a single gene disorder for which we have DNA prediction of a disease in a healthy individual. You're going to hear me say the prediction word throughout the afternoon because that is the difference. Huntington is a dominantly inherited disorder. It is a disease of brain cells, a loss of neurons, which results in an array of changes. You have a handout that lists many of the changes, looking at the physical changes, the intellectual and the emotional/behavioral. I try to present many things, which unfortunately may change the essence of the person over time.
In fact, the physical changes are often the things that the people find the least disturbing. It's the dementia and most of all the behavioral and emotional changes that are so disturbing to my families. The causative gene is at the distal end of the short arm of chromosome 4. It is one of the CAG-trinucleotide repeat mutations. If there are less than 30 repeats, that's OK. 40 or more, absolutely, without question if you live long enough, you will get Huntington. It's not a susceptibility, it's not a percentage, it's an absolute.
Between 30 and 39 used to be called the "Shade of Gray" area. Well, we've now uncomplicated that more by a little more knowledge as we've been able to fine tune even that intermediate level. Between 30 and 34, I can pretty much tell the person that they will be OK but this is a region of what we call meiotic instability, particularly if it's the dad who has the gene. The next generation can have an expanded allele and be affected with Huntington. Even though I can give the parent good news about themselves, they're not off the hook for their children. For repeats of 37, 38, 39, I can't tell absolutely that you'll get Huntington, but I'm worried. We do have some seniors who are doing fairly well into their sixties and seventies with that number of repeats, but we also have folks who are not. So that's not an absolute region, but it's an area of concern. 35, 36 that is the Shade of Gray. I really can't tell. That person remains at 50% risk or less, depending upon their own age and the ages of onset in other family members.
Again, the prediction of a healthy individual is so compelling . We're used to seeing kids and adults where we diagnose disorders when they come in with symptoms, and of course that's devastating but we know something isn't right. We're looking for an explanation; I'm sick, there's a problem, tell me what's going on. So there you're doing more confirmatory, diagnostic studies; there's something wrong, tell me what's going on. Whereas with the prediction, I'm coming in healthy. I'm coming in fine, but I'm at risk. And I'm at risk for something for which you can do nothing.
So much of our counseling is looking at weighing the risk versus the benefit, the value of knowing, the motivation for knowing. Because once I give you the test results, once you have your answer, you no longer have the option of not knowing. I can't take it back. So it's an issue that people have to face and feel very comfortable, feel very sure, about going forward. Let me tell you about two individuals who have come into this testing from very different backgrounds and you can see the difference that people enter with: