By Katie Jackson, President and CEO of Help 4 HD International
When I first began advocating for the Huntington's disease (HD) community going on 19 years now, one of the most striking things I encountered was how strongly individuals identified with their CAG repeat number. This genetic marker, which plays a critical role in the diagnosis of HD, became almost like a badge—a number that defined not just the disease but the person behind it. Over the years, I, too, began to identify myself and my loved ones by our first names, immediately followed by my husband’s CAG counts. It was an automatic reflex, a way to communicate our place in the HD journey.
But recent discussions and insights have led me to question what we are doing. Are we, as a community, placing too much emphasis on a number that might not be as fixed or definitive as we once thought?
The Science Behind CAG Variability
In a recent conversation with Dr. Peg Nopoulos, Chair of Psychiatry at the University of Iowa, and Dr. Nick McFarland, Associate Professor of Neurology at the University of Florida, we discussed the intricacies of CAG repeat numbers and how they relate to the progression of HD.
The generally accepted understanding is that a CAG repeat count of 36 or higher puts an individual at risk of developing HD. However, the exact number is not as straightforward as it might seem. In the lower range of 36 to 39 repeats, there is what’s called "partial penetrance," meaning that while there is a risk, the onset of symptoms can be highly variable. We in the community call this our Grey Zone. The variability in the onset and severity of symptoms becomes more pronounced as the CAG count increases.
Why the Numbers Aren't Always What They Seem
An important point raised in the conversation was the potential for a discrepancy in CAG counts. Laboratories that conduct genetic testing follow strict protocols, often adhering to CLEA certification standards, which aim to ensure the accuracy of the results. However, even with these protocols, there is a margin of error. A CAG repeat number might have a variability of plus or minus one, which means that a person initially tested with a CAG count of 39 might be retested and found to have a count of 41. This slight variation falls within the acceptable margin of error but raises important questions about the rigidity with which we identify ourselves by these numbers.
If the CAG number can change upon retesting, even slightly, should we really allow it to define our HD journey so definitively? Does a change from 39 to 41 (or vice versa) alter the course of the disease or the experiences we have along the way? The answer, as discussed by Dr. Nopoulos and Dr. McFarland, is that it does not. The number itself might vary, but the progression of the disease, and the impact it has on our lives, remains the same.
Moving Beyond the Numbers
Given this potential for variability, it might be time for us to rethink how we view and use our CAG counts. While these numbers are undeniably important in the context of diagnosis and understanding the genetic underpinnings of HD, they should not overshadow the personal and unique experiences of each individual affected by the disease.
Our focus should remain on the lived experiences of HD patients and their families—how we cope, how we find strength, and how we support one another. Whether your CAG count is 39, 41, what truly matters is the journey you are on and the community that stands beside you. You are NOT HD, and you are NOT a CAG. You are you, always remember that.
It's crazy that with these variable issues you people, HD Genetics, and the HDSA are still not accommodating to people.