Genetic Testing

We had another appointment with Dr Lam today. It has been a hot topic on one of the forums I frequent - the question of genetic testing. I asked Dr Lam about it today, I was neither for or against it but wanted to get his views and opinion. He has obviously heard of the SOX2 gene, and has said that if we want to, he is happy to connect us with a geneticist who can test for it. This is an excerpt from a forum about micropthalmia that covers some of the information about this testing:

One of the most alarming obstacles to getting Anopthalima/Micropthalmia kids tested properly is that most geneticists have never heard of SOX2 and other similar, recently discovered mutations and thus do not know about specific genetic causes of A/M. They simply do not know that such testing exists. Therefore, they are not testing for the right things.

I, too, had testing for genetic duplications and deletions; this is known as 'Micro-Array' or CGH (Comparative Genomic Hybridization) testing. Anyone who has this testing is taking a step in the right direction. But it's not enough. With greater research into the specific genetic causes of A/M and coloboma, the phrase 'genetic testing' is no longer an assurance. Testing done more than 5 years ago could not have included the new tests for mutations in the SOX2 and other genes because they weren't discovered yet. Geneticists have to know what to look for, and most don't. While my toddler Hillel's micro-array testing came out 'normal', he later tested positive for the SOX2 mutation.

This is from the website of ICAN, the International Children's Anophthalmia Network (www.anophthalmia.org). Note shaded sections:

SOX2 Gene: This gene was identified several years ago by researchers in England. Changes (mutations) in this gene have been found in about 15% of individuals with anophthalmia/microphthalmia. Typically an individuals has 2 working copies of this gene. If one copy is changed (mutated), it leads to anophthalmia/microphthalmia. Genetic testing is available for SOX2 and should be ordered on anyone with anophthalmia or microphthalmia.


And this:

It is NOT widely known to the public, or to doctors and even geneticists,
> that anophthalmia/microphthalmia (A/M) can have a genetic source -- my own
> geneticist at the prestigious Columbia-Presbyterian Hospital in New York was
> unaware of and thus did not suggest prenatal genetic testing for A/M-related
> issues. It is common for a pediatrician to tell distraught new parents of
> an A/M baby that the defect is a fluke. But A/M is much more common than
> even doctors realize, and in fact statistics show that the eyes are affected
> in 25% of genetic conditions. Thus there may be many people born with A/M
> who don't realize that they have a heritable condition. SOX2 is considered
> autosomal dominant, which means that even if only 1 parent has the
> condition, each child conceived by a couple has a 50% chance of having the
> syndrome. Knowledge of any genetic cause would therefore be of extreme
> interest to parents of any child with A/M not only for that child's sake but
> also for any other children the couple might have and any grandchildren they
> might see from the A/M child.
>
> I am writing to urge all parents of children with congenital A/M and/or
> coloboma to seek genetic testing. Since the SOX2 mutation was discovered
> only in the last decade, the urgency is not only for the sake of the
> undiagnosed individual, but for the very small group who has already been
> diagnosed: Among over 300 A/M cases who've been tested for SOX2 in a current
> research study, some 33 have tested positive -- that means that there are
> only 33 subjects to serve as precedents for my son. You can imagine how
> frustrating it is, as a parent, to have a child born with a condition shared
> by only a handful of documented cases; it is equally frustrating to know
> that there are thousands of people out there with genetic causes of A/M, but
> that it's so new that few neonatologists, pediatricians, or even
> ophthalmologists have even heard of it.

And this is a really great article:


http://www.news-medical.net/news/2006/05/16/17976.aspx


I know that's a lot of reading and I don't blame you for skipping it!

it does seem like there are two schools of thought, especially with PHPV. One that it's a fluke, the other that it's genetic. I would like to know for sure so that I can give all the information I possibly can to Joel so that when the time comes for him to settle down with an amazing, wonderful, gentle, girl (keep believing it!!) he can know if it is genetic and whether to be prepared for his children. It seems to be very, very rare, for two cases of micropthalmia to present in siblings, which is great news for us as we are expecting another baby in September! I really think that there's not much this next baby can throw at us that we won't be prepared and equipped to deal with after what we've been through with Joel.

At his check up today his eye looks good, still a bit inflamed so we are continuing with Maxidex drops 3 times a day instead of 2 hourly like we have been. Phew, that's a relief! It's hard going to remember to put drops in every two hours, and even harder to get Joel to let me do it. He is getting SO strong!