The results are in

[Katie]

The testing for SCS was negative, but Dr. Aughton was very clear in stating that it doesn't mean he doesn't have it. From the results letter:


These normal results do not exlude the possibility that Dillon may have SCS; roughly one third of people who do in fact have SCS have an underlying gene change that these studies can not identify. However, although I do still think Dillon probably has SCS, I do not yet know with absolute certainty that he does in fact have that condition, and I remain unable to offer a unifying genetic diagnosis with absolute certainty for Dillon at this time.

He went on to say that he does not have additional test and investigations to recommend for Dillon but would like to follow up with him. he also stated that some families like to get another opinion after a genetecist can not provide a difinitive answer, but we really like Dr. Aughton so I will make the follow up appointment and see if there are any other tests to check for SCS.

[mikaylasmommy]

Mikayla got the same exact answer when it came to the SCS. I am hoping once Mikayla has kids they will be able to test for all the genes.

[cheryl2]

Just curious, did they only look at the Twist gene? Or do they know of any other genes that cause SCS? Our reports (mine and Clara's) are identical. Both say
Mutational analysis indicates that the coding region of the TWIST gene is abnormal. The deletion of a cytosine at nucleotide 156 was detected. The presence of the mutation is consistent with a clinical diagnosis of Saethre-Chotzen.

Weird that just one little cytosine could cause so much trouble.

[vancesmommy]

:hugg I'm sorry you didn't get a clear answer! Sounds like we are in the same boat! They think Vance has C or C Like syndrome, but they can't give us a definite answer. I know how frustrating it is! I hope you get some more answers at the follow up appointment!

[verdon2]

:pray We can only hope for the best... for ALL of you. I can't imagine the uncertainty you all feel.....:hugg

[Katie]

Just curious, did they only look at the Twist gene? Or do they know of any other genes that cause SCS?

Thought the TWIST gene is usually the culprit, occasionally FGFR2 (exon8) or FGFR3 (exon 7) can be the cause. They did test both of those which were also normal. They tested exon 1 of the TWIST gene. I don't know what an exon is, I'm just reading off the report :lol

[Andi]

Oh, how frustrating! I'm sorry you don't have clear results after all this waiting.

Do you know the names of the tests they did? In my case (at CHOP) they did a PCR (polymerase chain reaction) and I came up normal; they followed that with a Southern Blot which indicated the deletion in the TWIST gene. They also tested the FGFR genes which came up normal.

I also had a FISH test for SCS done at another lab which also came back positive for SCS. So the FISH was able to detect my deletion.

If JH did all of this, then I don't know if CHOP's testing would be any better. But I can give you the names of the genetics people there if you'd like their info - just PM me.

:hugg

[Katie]

Andi,

I've looked over the report, and I'm not sure what the specific name of the tests they did were, other than "DNA sequence analysis". Does that sound like the same thing CHOP does, or is that a general term for genetic testing?

[Andi]

Andi,

I've looked over the report, and I'm not sure what the specific name of the tests they did were, other than "DNA sequence analysis". Does that sound like the same thing CHOP does, or is that a general term for genetic testing?

I can't find my lab reports right now, so I'm not really sure. I know that the PCR test involves amplifying (making bigger) a part of the gene around a certain area, so in this case around the TWIST gene. FISH, on the other hand, doesn't do this -- it uses a probe that looks at all the DNA of a cell and if it finds what it's looking for (such as a mutation or deletion in the TWIST gene) it will make that bit of DNA glow, so you can see it. So it certainly doesn't sound like JH did a FISH test, but whether they did PCR or Southern Blot I couldn't tell you.

Man, I've learned a lot about genetic stuff in the last 6 months! Oy! I'm sure you guys will get an education through this, too. If I can get my hands on my lab reports, I'll let you know what I find -- but I think my IVF clinic got a hold of my copies somehow. Hrm.

[KALEMSMOM]

Oh Katie...how frustrating. I couldn't imagine having to wait all of that time just to get inconclusive results. I really hope you get answers soon. They are getting more and more advanced with this stuff. Good luck and please keep us informed. I always found genetics sooo interesting.

[craniomommynbaby]

Awww...Katie, I wish you had a more definitive answer. I am not sure what test we had run for SCS, but they did specifically look for a TWIST mutation. I do not know whether they looked at the FGFR genes. They never mentioned the possibility of a false negative.
Simon's surgeons think we should test for Crouzon's next. If only we had the money...
We are with you in wanting to know answers. I am somehow doubtful we will find much. The features in our family have the geneticist and surgeons a bit puzzled. The ps has hinted about doing a paper on us.

[Matthews Mommy]

:hugg lots of love I know how frustrating this is, I will keep praying:pray

[Andi]

Katie -

I had to share with you what I learned today from my own genetic testing consult for our PGD. DH and I spoke with Dr. Mark Hughes, out of Wayne State U. (near you!) who is THE MAN in this whole PGD thing. I asked about why my PCR results showed that I was "normal" but the Southern Blot and the FISH test showed a deletion.

He explained that the PCR (which is a sequencing analysis) looks at the code of the TWIST gene itself. We all have two copies of each gene, one from our mom and one from our dad. For those of us with SCS, one gene has the mutation or deletion in the TWIST gene and one does not. If there's a mutation, they will see that the code is misspelled in that region. But if there's a deletion, all the PCR will see is the normal gene's code... because there's nothing there in the SCS's gene. This is why a different test (like the Southern Blot or FISH) has to be done. If I recall the Southern Blot test, it actually looks to see how much of each gene is there (they call it a "dose"), so if there's a deletion in the TWIST gene, there won't be as much of the gene in the SCS half as there is in the normal half -- the difference in "doses" shows there's a deletion. Hope that makes sense.

I suppose all of this could apply to the FGFR regions as well. So a test using DNA sequencing may not be the way to go, you may need a test that can detect deletions (like the Southern Blot they did at CHOP for me). That's all in my very amateurish opinion. :)

[Katie]

Thank you so much for that informaiton Andi! Dr. Aughton is wonderful in answering my questions so I am going to email him and ask him exactly what was performed at JHU, and weather or not a second test through CHOP might give us a more difinitve answer.

On a side note, WSU is pretty close to here! There are several people at work who will be going there this fall.

[Andi]

Hey Katie -- I'm trying to send you a PM but your mailbox is full. Can you make some room for my li'l message? :)

Yeah, Dr. Hughes' whole lab is based at WSU and it seems he's at the center of PGD research and testing. Kinda funky! In a little while I'll post another update, things are beginning to move along for us and it's getting exciting!