Q&A On Risk of Inheriting JHD
I do have a question though........some genetic abnormalities (not necessarily HD) are passed down more readily to a child of the opposite sex; like father to daughter or mother to son. I am wondering if that factor plays into inheriting HD.
To the best of my knowledge, no research has ever shown any sex-linked relationship in the inheritance of HD except for the change in the number of repeats from generation to generation.
When HD is inherited from the father, the repeats are likely to be higher than those of the father; when inherited from the mother, about the same.There is a lot of variability involved, though, especially when the father has HD. Thus, it is possible for the offspring to have fewer repeats than the father; and it is also possible, if the mother has HD, for the offspring to have somewhat different repeats.
Age of onset is associated with the number of repeats, so that there is a tendency among offspring of affected fathers for the age of onset to be earlier than that of the father; offspring of affected mothers tend to have onset at about the same age she did.
I have written to the group about my grandson, who my husband and I are raising, previously - but it has been quite a while, so let me give a little background.
My grandson's mother developed symptoms at age 15-16 and is now 24 (he is 4). His mother mom has a CAG repeat of 66. I know that HD sometimes is dramatically worse when passed from a father to a child; but might that also be true of a mother passing it to a child, when the mother has a high CAG; and could age of onset then be earlier?
"Worse" is a term which HD families and researchers might have trouble agreeing on. If Mr. A has more behavioral problems than Mr. B, but Mr. B has more chorea, who is worse? Furthermore, HD may give Mr. A more severe symptoms at onset but Mr. B more severe ones as the Disease progresses. Who has "worse" HD?
What most of us can agree on, though, is how fast the disease progresses (and most of us would say that if the disease progresses faster in Mr. A than in Mr. B, Mr. A has "worse" HD). So, if the father has HD, then the odds of passing more repeats on to his offspring are greater than those of passing on fewer repeats, and that means that earlier onset is more likely than later onset.
I believe that it is generally accepted that juvenile HD progresses faster than adult HD, so that the odds are that the offspring of a young HD father, if they inherit HD at all, will have it "worse" than the father.
In your daughter's case, if she passed the HD gene to her son, she most likely passed the same number of repeats to him that she has, so he will probably have about the same age of onset as she did, and the Disease will probably progress as fast in him as it has in her.
And in both cases (mother to child or father to child), does the child being the opposing sex than the parent have anything to do with severity of transmission to the child? (I know ANY transmission of the defective gene will be severe at some point in the child's life, but what I really mean is, with a mom who has higher than usual CAG repeats, would it be reasonable to expect a male child to have an earlier and more severe onset of symptoms, and would the answer to that question be any different if the child were a female?)
No. The number of repeats the child inherits has nothing to do with the sex of the child.
My grandson's grandfather - who was the parent passing HD on to my grandson's mother - is his late 40's and now is symptomatic, but it only began within the last couple of years. We have just recently learned that his brother - my grandson's great uncle (age unknown) is becoming symptomatic.
The dilemma we are dealing with is this: My grandson shows marked delayed development in every area - psychologically, cognitively, physically (coordination-dexterity). He is in a pre-K class for delayed children. Lately, he has been telling me his leg is 'shaking'. On one occasion, when I felt the calf muscle of his leg, it was indeed tightening and relaxing repeatedly. We had decided to not have him tested for HD, but now it seems more reasonable to do it, since the approach for helping him with his problem areas would be completely different if the reason behind them is HD, rather than some form of retardation or something.
I think the best thing would be to have him examined by a competent neurologist, one who has considerable HD expertise. If he thinks it's HD, he probably will recommend testing. None of us are neurologists, to the best of my knowledge, and you really needs an expert.
I think I am still just trying to sort it out in my own mind, and trying to make a wise decision about testing. I guess the biggest questions in my mind are: is there less of a chance that my grandson would have HD since he will have inherited it from his mother, than if he had inherited it from a father?
And, if he did inherit the gene for HD, would the time and severity of onset be expected to be later in life since it came from his mom, than it might have been if it had come from his dad?
Yes, on the average (meaning that out of 100 cases of paternal transmission, maybe 55-60 of them would result in more repeats and/or earlier onset).
With his mom having such a high CAG, could we realistically expect that his count will be at least as high, if not higher than hers? (I know that the higher the CAG, symptoms would occur earlier and more intensively).
The odds of higher repeats would be about the same as those of lower repeats.
Thanks for bringing up these excellent questions. You and your family are in a difficult situation, and I wish you the best. "The best" includes an early treatment for HD, and I firmly believe that will happen.
HDSA Tucson, Arizona Chapter