bicuspid aortic valves

[PathFinder]

Hi, guys!

I wanted to post such thread for long time ago, but I never had the time, so now it is

Bicuspid aortic valve is a condition whith very variable phenotypes - it can be found from the inafncy to people in their 11-th decade of life (e-medicine, 2006)! it may not cause any problems in the entire life, but in many cases causes very "bad thinks" to its owner.

Such problems include mainly regurgitation and stenosis, and not too rarely a aortic dilation with aneurism.

Bicuspid aortic valve carriers may live to their late 70's, 80's and 90's without concerning their congenital defect. Even more - some studies show the better survival of patients , operated after 60's to 80's, compared with the tricuspid owners.

However, having a BAV doesn't mean just having a defective valve and replace it. The Gene Engineering prove more evidently the deficiency of Fibrillin-1 proteine (or its mutation) as a major problem of the BAV. The point is, that the gene that encodes the Fibrillin-1 is the FBN1. It is very "responsible gene", because it controls the growth and tissue repairing in the organisms. It takes a major role in the development of the tissues and organs, in particular the vasculatory system, skeletal system and skin.

It is known, that the same gene is the causation of Marfan syndrome, Mitral Aortic Skeletal Skin phenotype and other connective tissue disorders.

There is some evidence of NOTCH1 gene-family, which corelate with the FBN1 (I'm not very educated in the biomolecular medicine). This NOTCH1 and FBN1 and Fibrillin-1 correlate with some Growth Factors defect (TGF b), which is responsible for the aortic development and indeed the whole left heart growth (incl. aortic valve, mitral valve and the connective tissue in the vantricles).

I have (had) a bicuspid aortic valve. Now I'm happy with my Sorin mechanical device, which till now works normaly. However I have been always diagnosed with mild mitral valve prolapse without regurgitation. My aortic measurments show no dilation, nor in the root or the ascendenta. Every Day I pray and thank to God, that I'm still not concerned with that, although my early AVR. I have always know (since I read medical literature), that the mitral prolapse is related to my congenital condition, in particular the connective tissue disorder, caused by the "crap genes" mensioned above.

I have read a lot of medical sources and I haven't found any corelation between the BAVD and the mitral prolapse. Probably it is more a result of more severe connective tissue disorder with just a presence of a BAV. Such disorder is Marfan syndrome. But the Marfan is related to skeletal disorders primary, and I am just the opposite side - I am strong, massive, with rounded head, with wide shoulders and good figure as proportions. And I have never have ocular problems. So - it is not marfan by me.

There is a syndrome, called MASS - Mitral Aortic Skeletal Skin phenotype. It is a condition similar to the Marfan, but little bit "softer". Its signs are a mitral valve prolapse, aortic root enlargement (but not very prone to become aneurismal), some skeletal defects (similar to the Marfans) and some skin disorders (stretchy skin).

Again, I don't have the skeletal disorder, but I have the mitral prolapse and have some little strinae on my lower back skin.

My cardiologists have never concerned other problems of my heart. They just follow the aorta, which haven't changed its size for 7 years (since my first echo in my life). They have noted the MVP, but have never discussed it like an issue and they have never disscussed any connective tissue disorder.

***

Today all I want to know is, whether my myocard is affected of the connective tissue disorder I have. The post AVR results are more than excellent: LV diametters are 30/45mm and the EF is 55-60% with normal contractile function, seven months post operation. I just pray for TWO LITTLE THINGS:

1. I only pray not have my myocard defected by the FBN1 gene disorder, because the Fibrillin-1 is a major component of the myocardial interstitium. That will allow me to have an easy life forward, without any complication caused by the native disease.

2. The most IMPORTANT thing for me...
I don't want to pass this crap to my children!!! NEVER! I don't know who can I talk to about the possibility of systemic connective tissue disorder in my organism, where the BAV is only a secondary disease. Do I have a MASS phenotype syndrome? And if I have it, what is the bigger chance to pass it to my children (because it is known, that such disorders have a 50% chance for inheritance in the child of a patient, while the BAV alone has some 15%).

Everything else is a piece of cake - the AVR, the anticoagulation, the normalization of late survival for AVR patients in the last years, even for younger patients (Loes Klieverik - AVR in young adults, 2007). These thinks don't bother me already.

Kind regards,

IVO

 

[alpha 1]

alpha 1

alpha 1

Pathfinder,
So how does fribrillin1 get mutated in the first place? I know its a really dumb question and probibly nobody knows really, well if they did then they could maybe cure it or prevent it or something. I have been reading up on this stuff not to the extent that you have because you really know a lot about it. My son has the bicuspid aortic valve. It needs repair hopefully we will be able to get that if we find the right surgeon. But like you said is that the end of it, just getting the valve taken care of. I just don't know. Have you read anything, though on what causes or what they think causes the mutation? It makes me feel really bad that probibly my or my husband caused this. Adam is 28 just about the same age as you, 6 ft tall always healthy or at least healthy looking, nothing wrong with his skin. Always looked really good. I just don't know how all of the doctors all of his life could have missed a heart murmer. Just don't know. If it is true about passing this on, does that mean if he has children that they will inherit this? It is really sad. If you have any more info on the subject please let me know, I am worried about other problems down the road, but we are praying a lot and I know everything will be ok. for you too, I will pray for you too. Well get back to me when you can.
Thanks for the info.
Janice

 

[CathyK.]

Pathfinder - I also had a BAV and still have MVP with a small amount of regurgitation. I asked it they would fix my Mitral valve when they fixed my Aortic valve. My doctor said no. He said replacing the aortic valve should help with the Mitral valve. I do have vision problem; near sighted and get optical migranes. I asked about the connective tissue disorder and the Dr.'s said no I don't have that. How do they determind that?? Like yourself, nothing else had been said about my Mitral Valve since they have been concentrating on the Aortic Valve. Lots of questions and not any answers. What to do??

 

[Susan BAV]

Ivo, I found your post very interesting.

Ivo, I found your post very interesting.

When my bicuspid valve was failing, my mitral was having fairly severe issues also. But my surgeon said that after he would replace the bicuspid and while I was still under, he would do a TEE; and when he did that, my mitral valve was working much better and happily didn't need repaired or replaced. I've read similar experiences from at least a few members here also.

Something else I have wondered is whether these valve issues are more likely passed on from the paternal side or the maternal side. This may sound ridiculous--sorry--but we've raised a few polydactyl felines and I have discovered from these experiences that, at least anecdotically, a polydactyl male is more likely to produce more polydactyl offspring in a litter than a polydactyl female; so this has made me wonder if there are other genetic issues that tend to come down either the paternal or the maternal side, in humans though. Muscular Dystrophy is an inheritable disease that also displays a particular gender preference.

More wondering... I have also wondered further about gender. Within my own family, there are no other known bicuspid valves aside from me; my father's side of the family, however, has had valve issues, particularly aortic valve issues. I have two sons and only nephews (no nieces) and mostly male cousins--males run strong in that side of the family--and no other known bicuspids. When I first began to research bicuspid valves, the ratio of diagnosed men to women with the disorder was something like 4:1. Why?

 

[PathFinder]

phenotypes

phenotypes

I am an industrial designer but I read a lot of things and I don't know how competent I can be in what I am writing on.

But I get much information on the propability, that the bicuspid aortic valve is a phenotype of a connective tissue disorder - CTD: that means, that not everyone with the mutated genes (related to this CTD) will have a BAV. Many of them will probably have a mitral prolapse, some will have septal defects, some dilated aortas with/without BAV and so... The point is, that the isolated BAV is the much frequent phenotype of the disorder. that is why many patients live with only a BAV finding, and as i mentioned, there are people's auropsies, where BAV has been found in 105 yearos.

So, I believe, that the bAV is just a secondary sign of another disease. But then again - I'm a designer and I am much more familiar with the Relative Theory of Einstein, than with the Gene Engeneering (seriously).

Ivo

 

[pamela]

Hi Ivo,

I read your post with interest and I understand your fears about passing on genetic heart disease or other inheritable conditions, to future generations. As in all things genetic, there are two major concerns; whether it is a recessive (sex-determinant) or autosomal (non-sex specific) chromosome. Primarily the connective tissue gene is an autosomal one, meaning that you can inherit from either parent. The odds of you passing the defective gene on are pretty good. From what I can tell from my reading, though, is that the trait isn't particularly dominant.

Marfans is a condition that will be diagnosed if you exhibit 3 or more of the classic characteristics in 3 different systems of your body: skeletal, skin, ocular, circulatory, neural, digestive and so on. There are specific morphologies particular to Marfans that you can research. If you have a direct ancestor with diagnosed Marfan Syndrome, you will only need symptoms in 2.

Ehlers-Danlos Syndrome patients have related but different symptoms and can usually be diagnosed through skin biopsy, which will usually be done if you exhibit the genetic characteristics through clinical observations and a detailed family history discussion.

eta: I have also discovered on closer reading that there is a blood test, Antinuclear Antibody Test to detect autoimmune
connective tissue disorders. It is not a definitive diagnosis but can help with prognosis and treatment options for sufferers of these diseases.

Mixed Connective Tissue Disease is an overlap of 3 specific connective tissue diseases and many sufferers exhibit auto-immune disorders in combination, diagnosis is made once a person has one of the diseases and has signs and symptoms of the others. When a person is showing undeveloped signs and early symptoms of connective tissue disease they are given a diagnosis of Unspecified Connective Tissue Disease. This feels like as big a catchall as Fibromyalgia and it is.

So, these problems are inherited but there's also the possibility that a spontaneous genetic mutation can occur on those genes that relate to fibrillin and collagen production in our connective tissue. Sadly, there is no cure but your doctors can treat the conditions that arise from these disorders. Well-informed is the first step in being well-armed. If you know that there are steps you can take to minimize the effects of the disease, you can take the required steps to modify your lifestyle to stay as healthy as possible for as long as possible.

The reason that more males seem to live long enough to be helped through valve surgery and aortic repairs/replacement is because these diseases make pregnancy extremely dangerous for the mother. I'm supposing that many undiagnosed women in the unenlightened past had many fatal or sterilizing difficulties with pregnancy. Now, thankfully, earlier diagnoses makes it possible to make childbearing decisions before they're made for us. That's just my theory and I make it from a gut feeling rather than any researched statistical facts.

 

[alpha 1]

connective tissue disorder

connective tissue disorder

Pamela,
When you were talking about the spontaneous mutation of the genes, what would cause it, any ideas? I took bendectin for morning sickness when I was pregnant, because I was so sick and throwing up all of the time. My aunt also took it, her daughter is ok. They took it off of the market after that because of birth defects. But that was mostly of the limbs. I wander what I did to cause this sometimes. I was young and rode my horse in my first couple months of pregnancy but I didn't fall off or anything. I cleaned house and probibly lifted things, but I guess people do worse things. I don't know. I wander if aspirin or tylenol could cause it. I never heard of any of this until the last couple of months. Who would even think of such a thing. I always worried about him going too far out into the water, riding motorcycles, running around with friends in cars etc. The normal things you worry about. Guess we all just have to do the best we can.
alpha 1

 

[pamela]

Thanks so much for helping clear up the inheritance concerns being expressed here Oaktree. I know that genetic diseases are beyond our choice and I'm glad you were able to reassure others.

Genetics is a medical specialty and just as important to those of us with diseases and conditions caused by our genetic history. It's not easy to live with but the fact stands that we are living and we have a good chance of living into our dotage.

It's not anyone's fault that we're this way, just as it's not anyone's fault if our eyes or blue or if we have big feet. We have the blueprint in our genes long before sperm meets egg and stirs our chromosomal soup up.

Take heart everyone. Medicine is keeping up with us.