Re: [MLUG - DISCUSSION] Holt-Oram Syndrome

["Jonathan King" <EMAIL:PROTECTED>]

On Tue, Mar 11, 2008 at 10:13 PM, Vern Green <EMAIL:PROTECTED> 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.

So you did not ask, but I would immediately talk to the cardiologist
about your hypothesis. I don't know if this would affect the treatment
plan any, but he or she would.

As you point out, Holt-Oram Syndrome is genetic (there are apparently
several different possible mutations in the TBX5 gene, a transcription
factor that plays an important role in cardiac and upper limb
development). Evidently, the severity of the phenotype can vary, and
it is something you would want to know about even if it had been
undetected so far. You may also be referred to a medical geneticist
who might be able to verify the genetic link. In any case, just to
clarify:

> 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.

In other words, the finger that would be a thumb does not correctly
"oppose" the other fingers and/or does not have the correct number of
bones?

> 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".

As it turns out, left sided hand abnormalities are more common in
heart-hand disorders.

> I decided, probaby against my better judgement,

Your judgement is fine. The possible discovery of the mechanism here
could be very important now and possibly also in the future. Getting
more knowledge here could not possibly be the wrong judgement. You did
very well. :-)

> 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.

See my comment above. Also, you might be able to find a gifted
orthopedic surgeon who could at least ameliorate the (less important,
to be sure) hand issue.

> 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.

I am not a medical geneticist, but I am pretty safe in suggesting that
you should consider seeking a referral to one. The 1 in 100,000
incidence you can look up doesn't necessarily mean that much,
especially since the syndrome does differ a lot in severity and there
are probably a lot of undetected cases out there.

> 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.

And that's why you should talk to your cardiologist and a medical
geneticist. If your insurance balks for some bizarre reason, you might
try to contact the appropriate people at a (hopefullly fairly close
by) research hospital or medical school. You may or may not be able to
secure a consultation and/or free testing that way, especially if you
can locate somebody who has a specific research interest in this
disorder. If your guess is correct, this is a relatively rare genetic
disorder, but its existence has shed important light on the function
of the so-called "T-box" genes (and vice versa: knowing what TBX5 does
will prove useful someday in understanding this and other disorders.

> No real question here, just some comments and some insight from those that
> deal in such things.

Let me know if you would like more information on this and I can try
to locate some expertise at NIH.

jking

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