After my genetic counsellor broke the bad news about my positive Huntington’s Disease result in my predictive testing, she informed me that my “CAG repeat score” was 42.

42 repeats. As I mentioned in a previous article, at that point in time, I was still quite ignorant about the science behind HD and the number 42 really meant nothing to me.

I quickly learned, however (remember the textbook?), that the number refers to how many times the gene repeats this cytosine-adenine-guanine section of the DNA within the Huntington gene.

Everyone has the Huntington gene within them. And everyone has a section of CAG that repeats. It’s only when the number of repeats passes a certain threshold that Huntington’s Disease will occur. Have a look at the following chart:

(source)

You can see that anything below 35 is considered a no HD zone. Then there’s the gray area between 36–39 where a person may develop Huntington’s Disease later in life. Above 40 is the full HD zone. In other words the “you’re screwed zone”.

Let’s have another look at my predictive test result below:

You can see my 42 there, but I also have a 20 from my mother. That 20 is normal, but the 42 from my father puts me in the “you’re screwed” zone of full HD penetrance.

This means that at some point in my life, I will develop Huntington’s Disease related symptoms.

But when?

I think that has got to be the most commonly asked question for those of us in these in-between years:

When will the cursed symptoms begin to take control of my life??

Unfortunately, it’s not an easy question to answer and there are a lot of unknowns, but again our dear friend science is able to provide some clues.

The data shows that, in general, the higher CAG repeat score you have, the younger you will be when symptoms develop.

I say “in general” because in order to see this correlation between CAG score and age of HD symptom onset, you need to look at a large sample of people.

Here’s a scatter graph to show what I mean:

(source)

This graph plots 319 Huntington’s Disease patients. The numbers along the left side represent age at onset of symptoms and the bottom number is the CAG repeat score. The relationship between CAG repeat and age of onset is quite clear, but what is also clear, is that there is still a great deal of variety and outliers there.

For example, let’s look at my number of 42 repeats. Tracking that up, you can see some people had symptoms begin in their 20's and others had symptoms begin in their 50's.

The general trend and correlation is there, but for individual people, the CAG can not be used to diffinitively predict age of symptom onset.

Here’s the data demonstrated in a chart:

(source)

In this chart, when using my good old 42 as an example, the median age of onset is 49-years-old. That, in no way, guarantees me an age of onset of 49. It’s just the median when looking at the Data from a large group of people.

Let’s remember my dad. His CAG repeat score is the same as mine: 42. And his age of onset was well above 49-years-old.

So, why the diversity?

There’s a lot of research going on right now to try and answer that very question and the answer is probably multifaceted.

What role does exercise play in the age of onset? What other genetic traits or biomarkers might a person have that contributes? Science doesn’t have the answers yet, but I have no doubt they will come.