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Aortic dissection, aortic aneurysm - The aorta - Life after an aortic dissection

A bit heavy but let's use this as a starter..

Genetic Basis of Thoracic Aortic Aneurysms and Dissections ("TAAD")
"In particular a gene called ACTA2 appears to be responsible for vascular (blood vessel) disease. The technical name for the mutation is G48V (DNA change G 190T in exon 3). In general, we have two copies of each gene, one from the father and one from the mother. If there is a mutation in a gene, then it may not work properly. In the case of the gene called ACTA2, mutations may lead to problems in the smooth muscle cells in the walls of blood vessels. When the gene is altered, these muscle cells may not contract as well as they should.

The blood vessel disease associated with mutations in the ACTA2 gene is passed on in a manner known as autosomal dominant. Autosomal means that males and females are equally likely to inherit a mutation, and equally likely to pass it on. Dominant means that a change in one copy of the gene is sufficient to lead to disease."
Please feel free to REALLY get some input into this.

(..And many thanks to Dan for his valuable input for this subject..)

Tags: ACTA2, TAAD, a, aneurysm, aortic, b, dissection, gene, genetic, type

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Actin is encoded in ACTA2 (gotta love Wikipedia) and Actin is called the aortic smooth muscle protein, so first impressions are this could be the culprit for dissections that occur "out of the blue"... As far as I am aware I have never had a genetic test. Due to the complexity of the data source, I assume that doctors need to suspect something fairly specific for the test to be of much diagnostic use. I imagine busying a weird woman wearing oversize plastic glasses, holding a pipette and squirting blue water into a tray of little glass things for an hour is also fairly expensive and hence testing everyone as a matter of course would be cost prohibitive. So, how would you get a doctor to have reasonable suspicion that you had an ACTA2 mutation?

Of the 3 congenital conditions i know of that predispose you to a higher risk of dissection, 2 are genetically detectable:
- Marfan's (caused by mutations in the FBN1 gene on chromosome 15)
- Ehlers-Danlos (Mutations in: Fibrous proteins: COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, and TNXB; or, Enzymes: ADAMTS2, PLOD1)
- BAVD (bicuspid aortic valve disease) <-- my case - as far as I know only detectable the "old-fashioned" way...

It should be worth noting, however, that the genetic tests are only used to confirm without a doubt that the suspected diagnosis is correct.

Has anyone here had an aortic dissection due to either of the first two congenital conditions? Or, has anyone found out that they had any of the first two conditions due to having a dissection?

What is the ultimate goal here? Blanket genetic testing to find out if you are genetically predisposed? Can you even reverse the mutation if detected? Does anyone know a geneticist who would like to talk to at least one confused person?
r
Richard,

It's a pretty absorbing subject but a lot of 'what ifs' and predispositions...yes u r correct its the aortic smooth muscle protein that is tested...Its not engraved in stone even if you have the genetic marker for this that you are more at risk..but it indicates a high degree of suspicion..other on the site HAVE had the tests for this..University of Texas did a focus test back in 2008 and the results were very positive re this being a culprit.

I have seen the private cost of this test in the US is about $750USD. Here in the UK the NHS does NOT test for this even if you wanted it ..BUPA might..even the UK genetic testing organisation does not mention it...

I for one am now asking my 2 brothers and children to have the test..as my position on this is if you have had an AD - and you - and your doctor believe that there were no real underlying reasons why it should have happened - ie high blood pressure, Marfans, car accident etc etc..it just might be that you do have a genetic defect that made you partial to AD.

I don't advocate that everyone should be tested for AD, however if it is in any way genetic it would be a wise move to have AD survivors family tested for it.. even if the test was not a true indicator it would still be worthwhile.

To start the ball rolling I have a call into BUPA to see (hope!) if I can find someone to discuss it with..fingers crossed..)

Others care to comment.?

cheers

Graeme

http://ejcts.ctsnetjournals.org/cgi/content/abstract/31/6/970
http://www.gig.org.uk/services.htm
http://www.bcm.edu/pediatrics/index.cfm?Realm=99992426&This_Tem...
http://www.library.nhs.uk/geneticconditions/viewresource.aspx?resID...
http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=taa
Hi Everyone.
I have a grim family tree regarding vascular diesease,heart attacks,strokes, but as far as i know i'm the only person to have dissected.
I dissected back in 2003 and got to thinking that maybe just maybe that instead of my grandfather dying of a massive heart attack and a couple of uncles too that one or two could have dissected and just put down to heart attacks.
with no real post mortem bein carried out it could have been the case.

Plus my father having cronic heart problems starting at the age of 45.
My mother too suffered ischemic vascular diesase but i think her smoking was the contributory factor there.
I was concerened that there maybe a link genetically and as i have two sons (need i say more)
I was and still am a member of an a/d forum based in america.
I'm not sure if the founder of the forum contacted the university of texas or if the university approached members of the forum.
But in my case bein here in the uk i sent an email to the study team asking if they would consider me.
They were happy to include me in the tests and sent me (free of charge) 7 testing kits consisting.
I have a small number of blood relatives that im still in contact with.
My sister/brother/my aunt & her son/my two sons and of course me.
Logistically it wasn't to hard to do as were all in close proximity apart from my sister but i posted her kit she did the test and posted back to me to be shipped off with the other kits.
The results came back and i hope you don't mind Graeme but will copy and paste some of the data i recieved.

Dear Mr. ------,
Thank you for your participation in our research study entitled the Genetic Basis of Thoracic Aortic
Aneurysms and Dissections ("TAAD"). The purpose of this letter is to discuss some research results we obtained using a biological sample that you provided. You may want to keep this letter with your medical records and other important documents, so that it is available for future reference. Please feel free to discuss it with your family members and your medical providers, if you wish.
As you know, several members of your family have been diagnosed with abnormalities of the blood vessels, including aneurysms (widening or ballooning of the blood vessels) and dissections (lengthwise tears along the blood vessels), as well as other conditions that may be related to blood vessel problems, such as coronary artery disease (which can lead to a heart attack) and stroke.
In the course of our research, we discovered a mutation (a change) in a gene called ACTA2 that appears to be responsible for the vascular (blood vessel) disease in your family. The technical name for the mutation
is G48V (DNA change G 190T in exon 3). This mutation appears to be present in those family members who have developed vascular problems and absent in adult family members who have not developed these conditions. Note that some adult family members without vascular problems have been found to carry the mutation. This means that they may be at higher risk to develop a vascular problem in the future, even though it has not happened yet.
Per your request, all family results will be outlined in this letter. Unfortunately, your eldest son, ------ and your sister ------ have the mutation. Your other son ----, your brother ------ and maternal aunt ----- and cousin ----- do NOT have the mutation.
As a reminder, genes are the information that we all receive from our parents and pass on to our children. This is information about our physical appearance, as well as about how our bodies grow and develop. There are thousands of genes. In general, we have two copies of each gene, one from the father and one from the mother. If there is a mutation in a gene, then it may not work properly. In the case of the gene called ACTA2, mutations may lead to problems in the smooth muscle cells in the walls of blood vessels. When the gene is altered, these muscle cells may not contract as well as they should. The blood vessel disease associated with mutations in the ACTA2 gene is passed on in a manner known as autosomal dominant. Autosomal means that males and females are equally likely to inherit a mutation, and equally likely to pass it on. Dominant means that a change in one copy of the gene is sufficient to lead to disease.
As part of your family's participation in our research study, you contributed a sample of saliva. From this sample, we extracted DNA to be analyzed for the gene mutation that was detected in some of your family members. The result of this analysis was positive. That is, you were found to carry the Rl49C mutation in the ACTA2 gene that was detected in other members of your family. We have published data showing that alterations or mutations in this gene cause a predisposition to thoracic aortic aneurysms and dissections. We have unpublished data showing that alterations in this gene also lead to vascular diseases due to occluded (blocked) arteries, including coronary artery disease and strokes. Although we have not seen you as one of our clinical patients, we are recommending the following procedures for your medical management based on our research data, your family history of vascular disease, and other patients that we have seen with this mutation. Please use this infonnation to develop a care plan with your primary care provider and your cardiologist.

There's a few more pages but thats probably the nuts and bolts of the results.
my worst fears that one or both of my sons would have this mutant gene were confirmed.
My eldest son who has the mutant gene is in the armed forces and has decided to just carry on as normal and forget about the gene (kinda scary) but i'll keep at him when the timings right and get him to have a scan.
His fear is that if any of this comes out he'l be binned on medical grounds.
I've told him that that wouldn't be the case but hey i can see where he's coming from.
(three tours of iraq and currently in afghanistan as of two days ago for a six month tour of duty)
My sister is i think 54..ish and has contacted her G.P who was very interested and has booked a scan for her via the N.H.S. still waiting for appointment but shouldn't be too long.
i'll tell you her results when i get them.

Well have a read of this and any qusetions/feedback we'll see where it takes us.
Warm Regards
Dan............
TODAY IS A GOOD DAY :O)
is the test still going? it would definitely be worth piggy backing along where possible... thanks for the background, after my AD my direct family was tested for a bicuspid aortic valve. Luckily it seems to have skipped them...
r
Richard,

Don't think so. It was back in 2008. I will contact the University of Texas and see if they are intending to do another one...

Dan,

I am VERY INTERESTED that the NHS is doing a 'test' on your sister....is it a scan (ultrasound, MRI) or is it a genetic marker test? If its an ultrasound scan it will show any abnormality (widening etc) of the aorta (The NHS is instigating scanning UK wide by 2011 for all men over 65 for AAA (Abdominal Aortic Aneurysm) but of course it wont show any genetic disposition. I was of the understanding that the NHS could not/would not(?) do the genetic test for this..??

cheers

Graeme
Hi Graeme.
It's a ct scan with contrast that my sisters GP has put her forward for.
Regards.
Dan
Dan..
OK - so NOT a genetic marker test...thought that it was too good to be true..the NHS using genetics as a health tool! Back to the drawing board - seems no-one in the UK is interested in genetic screening as I have heard back from BUPA - a big NO unfortunately..Anyone know if any of the other health insurers will do this i.e. AXA etc..?

cheers

Graeme
Graham

After my repair in August my Surgeon Professor Julian Scott who I believe is one of the leading thoracic surgeon in the UK asked me if I had a heap of cash what would “people like me want to know,” at the time I approach others on the American site to see what others would want to know about their condition through investigation, unfortunately I didn’t have much feedback and at the moment I am still preparing a paper with some ideas and thoughts. As for myself, I have been told that it was high blood pressure that caused my condition, and I seem to remember at some point that they collected a day’s urine and I was told it wasn’t genetic but I was extremely ill at the time so I’m not certain. I do know that Leeds has money available for investigation into thoracic conditions and if we can make a case it might be possible for us all to get involved.......... anyone interested!

Marion
I too was repaired at Leeds, in my case at the end of November 2009. I have my outpatient appointment in mid Feb with my surgeon, Mr RU Nair, and I will take the opportunity to ask some questions such as:

Did they have any indication of my AD being caused by something other than my high BP? Did they run any tests?

How many ADs do they see each year at the Yorkshire Heart Centre? I assume quite a few as it seems to be a local centre of excellence for cardio-thoracic surgery.

I also have some personal questions such as how far I dissected. I know type A but did it descend.

Has anyone any suggestions for other questions? I will publicise this group as well.

On the subject of family screening, the GPs for my family members seem happy to refer them for at least ultrasound screening following my AD. My father has had his and my mother and brother will do so soon. I assume if anything appears they will then have CT scans.

Charles
I think in the words of General Patton (excuse the reference!) we have some serious traction going here.. !

Re high blood pressure..yes and yes..BUT at least 30 (minimum!) per cent of our western civilization also have it as well..so why do/did only us exclusive lot dissect..???

Granted it is a factor - but it's NOT the sole reason..I am not fit to hold a test tube let alone make speculative diagnosisis (is that a word!?) on this subject but I am adamant that there is a genetic marker involved in many cases of AD...

ie high blood pressure + ACTA2 genetic marker = AD - but high blood pressure by itself does NOT = AD..

I'm with Marion here as if we can put together a half decent paper I think we can really get something going.. If everyone could have a think over the weekend on this..as I would like to get it put in front of my surgeon as well - plus some other pretty eminent thoracic surgeons..plus NHS (got a good contact now!) plus BUPA, AXA etc...

more later..

'aveagoodweegend...'
(aussie for having a lovely weekend!)

cheers

Graeme
Hi Marion.
I remember you puting a post in the American forum and yes i saw there wasn't a lot of input.
I did put in a reply saying i thought it would be great if there were a central fund for G.P's to draw from so they could arrange for people to be scanned if a family member/members suffered an A/D or cronic vascular diesease.
And that it would also be a great idea to educate A&E departments in earlier diagnosis.
I dont think we'll ever get to the stage where it's standard to scan someone presenting with simular symptoms as a heart attack after finding the E.C.G. to be contrary to that diagnosis.

I know and do appreiciate that it's hard for A&E departments to diagnose dissections but surely if the E.C.G comes back with negative results then the next thing should be to look deeper rather than go for the cheaper option of lets wait a while and take a few blood tests
It always seems to be the case of well ok lets wait a while and we'll do some other tests (cheaper ones)

Marion.... regarding your blood pressure causing your dissection i'm sure that it was a contributory factor but i asked my consultant the same question.
He said yes i believe that blood pressure made the aorta dissect Dan like it does with numerous others but what we dont understand (we being the medical profession) is why high blood pressure causes dissections in one person and not in another?
i'd already started the ball rolling regarding gentics with the texas study he was quite interested but nothing came of it but i think that was more my fault not his for not pushing further.
He's a great vascular surgeon and has looked after me from the off.
Dan
i don't know whether this helps, but it appears the standard procedure here is to send people who present with heart attack symptoms but with no real indication on an ECG straight for an intracardiac (heart) catheter.

i am a little confused as to symptoms too. i don't think that is relevant here however, so i will post in the awareness topic, or maybe start a new one off...

having a 65% good day ;)
r

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