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Huntington's Disease Youth Organization

Can 2 brothers get infected at a wide age gap?

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Q. My Grandpa had Huntington disease, 3 of his children developed HD when they were at the age of 25-30 years old, the other 3 brother (my dad included) didn’t develop any symptoms of the disease, one of the three got tested at the age of 40 and he doesn’t have the gene.

My dad never got tested and doesn’t want to, he is at the age of 50 now and thanks god haven’t got any symptoms so far. New researches' indicates that there is a relation between the number of trinucleotide repeat and the age of the disease outbreak. If my uncles got HD at the age of 25-30 and my dad is 50 years old and didn’t have any symptoms so far - does it mean that he don’t have the gene at all? Can 2 brothers get infected at such wide age gap?

I’m 25 years old and I don’t want to get tested yet.

Looking forward for your answer.

Eliel, 25, Israel

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A. Dear Eliel,

Sorry about the late reply but I have been unwell.

When someone, such as your grandfather, has the gene for HD then each child has a 1 in 2 or 50:50 chance of inheriting the gene. The risk for each child is independent of whether or not any other children inherit the gene.

As you mention, the size of the CAG or trinucleotide repeat heavily influences the age of onset. In general, the larger the CAG repeat the earlier the age of onset. The 3 siblings of your father were affected before 40 and probably had large CAG repeats.

When the gene is passed on from a father to either a male or female child there is a small chance that the size of the CAG repeat will increase at conception. Thus, it is possible that a father (your grandfather in this case) had a lower CAG repeat number than his affected children who could then potentially develop symptoms at a younger age than him. This phenomenon is known as anticipation.

The only way to know if your dad has the gene is for him to have the gene test. This is because either he did not inherit the gene for HD or because the size of the CAG repeat did not increase when he was conceived (i.e. no anticipation). If the former is the case then he can’t get HD & your risk is effectively 0%. If the latter is the case then he will one day get HD, but no one can tell him when, and your risk is 50%.

With respect to getting the gene test, most people chose not to be tested. I would see this as a legitimate choice. Likewise, getting the gene test is a legitimate choice. That is, predictive testing is a personal matter for the at risk individual and as we are all different a doctor like myself cares only that each at risk person has the chance to make their own decision,

All the best,

Andrew