Re: [MLUG - DISCUSSION] Holt-Oram Syndrome

[Mike Miller <EMAIL:PROTECTED>]

On Tue, 11 Mar 2008, Vern Green wrote:

> As most of you know, my wife and I recently had a son. The happy time of 
> our life was marred by the discovery that our son has both a ventricular 
> septal defect and an atrial septal defect. We were concerned as all 
> parents would be, but have been watching him closely and have been 
> getting medical care from the hands of a very gifted cardiologist.

Vern -- I am so sorry to hear this.  I was wondering if things were OK 
because I wasn't hearing as much from you lately.  Hang in there.


> So today I was looking at his teeny little hands, and noticed an oddity 
> on his left hand. It appears that he has five fingers on his left hand. 
> Baby hands are kind of chubby and this is just starting to become 
> apparent. His left hand is clearly different than his right, which 
> appears to be more "normal".

I think I get it -- his thumb looks like a finger, right?  And he has 5 
digits on all extremities?  Do you have a photo?


> I decided, probaby against my better judgement, to look this up hand 
> defects on the Internet and found Holt-Oram Syndrome. It seems like it 
> is rare, 1 n 100,000 have it, but it appears it is genetic. Neither my 
> wife nor I have any knowledge of this ever occurring in either of our 
> families, however, my wife is not so sure about her father's family. It 
> is apparent in my reading that unless he has other bone issues we are 
> not aware of, we are already aware of the most dangerous part of the 
> disorder. I will just have to find ways for him to cope with the teasing 
> he is bound to get when he gets to school.

OMIM is the place to go for technical info:

http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142900

That sounds like something definitely worth looking into.  There is a lot 
of heterogeneity with different mutations of the gene causing different 
effects.  I'd guess that a lot of the cases are due to new mutations so 
that you don't see others affected in the family.

Your son might have this syndrome, or some other genetic syndrome.  Your 
observation of the hand abnormality is undoubtedly a very important clue.


> Since this is a genetic disorder, and I know some on this list deal in 
> genetic probabilities and such, I thought it would be interesting to 
> throw this out there and see what the professionals have to say about 
> it.

No problem.  Here are a couple of things to note:

(1) I do know a lot about genetic transmission of disease risks but not 
specifically for this disease.  You definitely should seek genetic 
counseling if your insurance will cover it.

(2) New mutations causing dominant genetic diseases are more likely in 
older fathers than in younger fathers, so the 1/100,000 might increase 
several fold for your age group.  Nice paper on this topic:

http://taxa.epi.umn.edu/~mbmiller/journals/nat_rev_genet/200010_Crow_mutation.pdf

(3) We don't know if your son has the Holt-Oram syndrome, but even if he 
does have it, he might be the only one in your family.  If he does have 
it, *probably* half of his children would get it from him.


> We currently do not have a clinical diagnosis of this, merely a syndome 
> that matches the symptoms. I am more worried about the possibility of 
> one of my other two sons having the problem, even though they have never 
> been diagnosed with any sort of problems. Both are healthy for 10 and 12 
> years old.
>
> No real question here, just some comments and some insight from those that
> deal in such things.

Your insurance should pay for tests.  I can't tell you the probabilities 
because not enough is known about the mutation rate in this disease, if 
your son even has this disease.  But there seems to be a good chance that 
your son is the only one with the bad gene, if he has it.

The good thing is that analysis of the TBX5 gene should answer many of 
your questions.  There are probably some researchers interested in 
whatever problem your son has and they would probably help you, at least 
by providing some genetic tests.

My best wishes to you and your family,

Mike

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