Advanced Maternal Age Associated with AIS?

[Pooka1]

I just couldn't help myself from interjecting at the thought that ANYONE could really believe that there are no effective therapies for most "genetic" diseases.

That was hdugger's idea which I disagree with. She seems to think a genetic etiology requires a surgical treatment per se and that conservative treatments are ruled out. That is clearly not the case.

[hdugger]

Might I add that the Scoliscore test could only be beneficial if all AIS cases are in fact genetically caused.

I think it might be beneficial for predicting what I consider to be the "perfect storm" of scoliosis. Assuming there are not extreme conditions in the environment (severe nutritional problems such as rickets, say, or maybe some extreme muscle disuse) I consider some amount of genetics to be necessary preconditions. So, it seems that you have to have a specific body type, and probably some kind of hypermobility in the joints. Probably other preconditions as well.

Again, assuming all that, the Scoliscore test might roughly divide people into those who have a preponderance of those characteristics and those who don't.

If it does that well enough, what then becomes interesting is those people who one would assume have the perfect genetic storm (the ones with high scores) who *don't* progress. Presumably, something in the environment has gone right for them.

This is only interesting if the Scoliscore is tracking something other than obvious physical characteristics. (And, of course, if it works in practice) So, you might well come up with a genetic test which measured one's likelihood to get skin cancer, but if it only measured the factors which control skin pigmentation, it's just putting a fancy bow on something we already know.

BTW, the people who developed the Scoliscore test don't recommend relying solely on it. That would indicate that they don't consider is completely genetically deterministic. If they did, they could have a child take the test and, sight unseen, prescribe their treatment. In fact, if they considered it completely genetically determined, they wouldn't wait for the results of the test to pull kids out of braces, since, presumably, they'd believe that bracing didn't matter for anyone. They'd just take the occasional xray of the high-scoring kids to see if they were ready for surgery yet.

[Dingo]

hdugger

Spot on. The only thing I would add is that some people believe that there is a Scoliosis "gene" that does more than raise the risk of severe symptoms. They believe that Scoliosis is fundamentally triggered and spread by heredity. I strongly disagree with that line of reasoning based on the fact that no childhood, genetic disease is as common as Scoliosis. Not one. Zero. Based on countless thousands of hours of reading I strongly suspect that spinal curves are triggered by a nervous system disorder that is set in motion by environmental damage, probably from a pathogen. Time will tell.

Could heredity increase or decrease the odds of getting Scoliosis? Probably. Just like every other disease.

[rohrer01]

This is right off of the NSF Welcome page:

"New Study Shows DNA Test Highly Accurate In Predicting Curve Progression in Scoliosis Patients

Peer-Reviewed Study Shows Genetic Markers Can Help Identify Low-Risk Patients, Potentially Reducing Need for Repeated X-Rays and Physician Visits

Raynham, MA – (December 1, 2010) –A new study shows the SCOLISCORE™ AIS Prognostic Test, a DNA test to determine the likelihood of curve progression in children with mild adolescent idiopathic scoliosis (AIS), an abnormal curvature of the spine, is 99 percent accurate in predicting which children are least likely to progress to a severe curve (Cobb Angle of 40 degrees or more). [1]"

If the Scoliscore is really 99% accurate, what's the argument about? I realize we have to protect the 1% so follow-up monitoring should still be done (in my opinion), maybe just not as aggressively.

Dingo,

I think we've been over this before. "Genetic" diseases can certainly be triggered by environment and to say scoliosis is "genetic" does not mean that there is a Scoliosis Gene, per se. Genetics is waaaay more complicated than that in many cases, unless we are all green or yellow peas. There can be several genes that contribute to the overall disease process. Scoliosis appears to be one of these diseases. For example, in my own family, affected individuals skip generations. This would lead one to believe that this is recessive, right? But wait, now add that all the affected individuals are female. Now is it X-linked or recessive? I really don't know, but there are four affected individuals over a 4 generation span and my father was an only child, so he HAS to be the common link, yet he is unaffected. But my father's mother was affected and also my sister's daughter and myself and my daughter (to a mild degree). It's not reasonable to think that someone born in 1916 had the same environmental exposure as someone born in 1990, being that they were raised in different regions and some had different cultural practices. Because there have been so many different hereditary patterns found, I would suffice it to say that there isn't only one gene, hence the "Scoliscore". I don't think anyone would argue that it isn't plausible for there to be environmental triggers as well. (sorry about the redundance) So for the 1% of children that don't have an accurate scoliscore, then perhaps environment does play a significant role. But for the 99% of the rest, it is accurate.

Just out of curiosity, have you had your son tested? Here's your chance to prove yourself (I realize that one child isn't going to make or break an argument, but it may convince you either way). It would be interesting to know the outcome as you have him in some pretty rigorous training that will ultimately be physically good for him either way, I'm sure. I'm just wondering if he scored high and he ultimately doesn't progress, then your hypothesis may have some validity AND you may be able to help other children by sharing your techniques. If he scores low and progresses despite the exercise routine, your theory may also have a leg to stand on and you may convince others to look further into your ideas (or the exercises actually proved to be harmful - still environment). However, if he scores high and progresses despite the exercise routine, you may reconsider your position on the matter. You are an intelligent man and if I remember right you have at least one friend that is a physician and may be able to order the test for you. I think it would be worth it. The best thing that could happen for your son is that he scores low and doesn't progress. This wouldn't necessarily back up your point and would indicate that perhaps scoliscore is an accurate predictor after all (although I'm not sure it will convince you), but the little guy will also end up with a strong healthy back. My personal guess is that he will score low and not progress. But that's just my hypothesis based on the information that you have posted about him.

[rohrer01]

I think people are arguing nonsense here. This same argument seems to keep appearing. Genetic vs. Environment.... Many, many, and I stress MANY "genetic" diseases are caused by environmental Factors. Anything that causes damage to a gamete (sex cell) can cause a genetic disease. A couple of examples are radiation and chemical toxins, whether exposure comes accidentally or by consumption of something or smoking or whatever. Just because something in the environment causes the damage doesn't mean it's not genetic. The two ideas aren't as polarized as people are making it sound. That's the last I will say on the matter of genetics vs. environment. It's like arguing "nature vs. nurture", there is a component of both. If we know the current etiology of a problem, despite how it started, it may or may not help in treatment options, but at least it's a starting point.

[hdugger]

Dingo's son isn't in the target audience for the test, which is only meant for AIS (not JIS) children. I think JIS is considered way too unpredictable to try and develop a test.

It would be interesting for those of us who already know how the story turned out to go back and test our kids. I doubt the insurance company would subsidize our curiosity, but still, it would be interesting.

[hdugger]

Just because something in the environment causes the damage doesn't mean it's not genetic. The two ideas aren't as polarized as people are making it sound.

I think much of the environmental interest is in things which don't affect genes. So, can a vitamin D deficiency play a role in scoliosis? Or, can bracing change the course of the disease.

The "pure" genetic argument here would say no--the genes are the only things which can play a role, and nothing else will make a difference. To me, that seems overly fatalistic, even for a disorder in which genetics play a role. But, that's the crux of the argument.

[rohrer01]

"The "pure" genetic argument here would say no--the genes are the only things which can play a role, and nothing else will make a difference. To me, that seems overly fatalistic, even for a disorder in which genetics play a role. But, that's the crux of the argument."

My reason for this argument was that back in the thread, Dingo cited a study that said cigarette smoking and BC pills increase Down's Syndrome as an argument for "environment".

Yes, I also forgot that Dingo's son has JIS. You are absolutely right about not being the target audience. However, I was in the study that helped develop Scoliscore. I think it would be interesting to know what my score is just for curiosity sake, even though I will never find out.

[Ballet Mom]

Scoliscore determines the risk of progression, not of incidence.

Yes, so we'll just play the odds on our kids and hope they don't progress. If Scoliscore can't even give a definitive answer on whether the kids who score 1-10 will end up with a progressive curve or not, it's not much of a help.

[Ballet Mom]

This is right off of the NSF Welcome page:

"New Study Shows DNA Test Highly Accurate In Predicting Curve Progression in Scoliosis Patients

Peer-Reviewed Study Shows Genetic Markers Can Help Identify Low-Risk Patients, Potentially Reducing Need for Repeated X-Rays and Physician Visits

Raynham, MA – (December 1, 2010) –A new study shows the SCOLISCORE™ AIS Prognostic Test, a DNA test to determine the likelihood of curve progression in children with mild adolescent idiopathic scoliosis (AIS), an abnormal curvature of the spine, is 99 percent accurate in predicting which children are least likely to progress to a severe curve (Cobb Angle of 40 degrees or more). [1]"

If the Scoliscore is really 99% accurate, what's the argument about? I realize we have to protect the 1% so follow-up monitoring should still be done (in my opinion), maybe just not as aggressively.

Dingo,

I think we've been over this before. "Genetic" diseases can certainly be triggered by environment and to say scoliosis is "genetic" does not mean that there is a Scoliosis Gene, per se. Genetics is waaaay more complicated than that in many cases, unless we are all green or yellow peas. There can be several genes that contribute to the overall disease process. Scoliosis appears to be one of these diseases. For example, in my own family, affected individuals skip generations. This would lead one to believe that this is recessive, right? But wait, now add that all the affected individuals are female. Now is it X-linked or recessive? I really don't know, but there are four affected individuals over a 4 generation span and my father was an only child, so he HAS to be the common link, yet he is unaffected. But my father's mother was affected and also my sister's daughter and myself and my daughter (to a mild degree). It's not reasonable to think that someone born in 1916 had the same environmental exposure as someone born in 1990, being that they were raised in different regions and some had different cultural practices. Because there have been so many different hereditary patterns found, I would suffice it to say that there isn't only one gene, hence the "Scoliscore". I don't think anyone would argue that it isn't plausible for there to be environmental triggers as well. (sorry about the redundance) So for the 1% of children that don't have an accurate scoliscore, then perhaps environment does play a significant role. But for the 99% of the rest, it is accurate.

So you'd be okay with the fact that your family members could progress to 40 or 45 degrees and sometimes greater than that and the Scoliscore test would still be considered a success?

[rohrer01]

I would never be happy with progression, for ANYONE. That's extrapolation to the extreme. Scoliscore is just another tool that we can use to lower the exposure of low risk kids to x-rays that may not be needed. The more tools I have in my pocket the better. Nothing in this world is guaranteed. Wow!

[Ballet Mom]

Scoliscore is designed so that if someone progresses to 40 degrees, their test is still considered successful. So even if someone scored 10 on the Scoliscore and progressed to 40 degrees it would fall within the test parameters. And some kids will progress to greater than that, and that will also be expected to happen with this test (and has). So if you increase the x-ray interval to a year instead of six months, a whole lot of kids will progress to those levels, no one knows which kids are actually going to progress or how fast.

I certainly wouldn't take that gamble with my child.

[hdugger]

I think we're still drifting off course with the genetic discussion. Somehow we keep ending up in academic definitions, when what we're really interested in is practical issues.

In terms of the current discussion, the only meaningful definition of a genetic disease is one which is familial and over which we don't have any control. If something in the environment causes a mutation, that may be genetic in academic terms, but it's environmental in the sense that it's something we can change.

[Pooka1]

I think people are arguing nonsense here. This same argument seems to keep appearing. Genetic vs. Environment.... Many, many, and I stress MANY "genetic" diseases are caused by environmental Factors. Anything that causes damage to a gamete (sex cell) can cause a genetic disease. A couple of examples are radiation and chemical toxins, whether exposure comes accidentally or by consumption of something or smoking or whatever. Just because something in the environment causes the damage doesn't mean it's not genetic. The two ideas aren't as polarized as people are making it sound. That's the last I will say on the matter of genetics vs. environment. It's like arguing "nature vs. nurture", there is a component of both.

Yes. It is impossible to discuss any of this if the bunnies go off on a different directions and start defining words and then misunderstanding. The researchers get to define the words in their field and the bunnies are then obligated to understand that and learn it and use it in the same way. We don't obtain that result here and elsewhere.

If we know the current etiology of a problem, despite how it started, it may or may not help in treatment options, but at least it's a starting point.

Bingo. The leap/connection between etiology and treatment mode (conservative versus not) some are trying to make here is not a valid move. But it was eye-opening to me in terms of why folks resist facts about the consensus of the research community and why we constantly need mini monkey trials here. The resistance to the idea that AIS being genetic has come up before and Pnuttro tried to field a reason for it. She may be right or wrong but there is necessarily some reason for resistance to facts among the bunnies. And the reason that they tie it in fallaciously with treatment modes is a good candidate reason in my opinion.

[Pooka1]

I think we're still drifting off course with the genetic discussion. Somehow we keep ending up in academic definitions, when what we're really interested in is practical issues.

In terms of the current discussion, the only meaningful definition of a genetic disease is one which is familial and over which we don't have any control. If something in the environment causes a mutation, that may be genetic in academic terms, but it's environmental in the sense that it's something we can change.

There is no higher potential to cure AIS if it environmental versus if it is genetic. You can't make that move because it is likely a bad assumption. It might be easier to solve if it is strictly genetic. Who knows.