Advanced Maternal Age Associated with AIS?

[hdugger]

Hey, you're already right. Without your steady persistence, I don't think we would have pursued exercise as strongly as we did. With that, my son has managed to reduce his discomfort to nothing, substantially improve his appearance, and hold his curve steady (or even reduce it by a few degrees). It's made a tremendous difference for his college years, which was really all we ever asked.

So, see, you're right already

[hdugger]

Oh, I see I should have gone to the Scoliscore site for an analysis of the relationship between genes and scoliosis.

So, they have a fascinating article at http://www.scoliscore.com/scoliscore...icLinkage.aspx

In it, they say that research suggests a multifactorial cause of the expression of scoliosis. That is, you can carry certain genes, but only develop scoliosis in the face of a variety of environmental factors. Or, as they state - "A complex disease is caused by the interaction of multiple genes and environmental factors. Complex diseases are also called multifactorial. Examples of complex diseases include cancer and heart disease."

They also talk about the genetic makeup making on susceptible to the disease.

So, anyway, pretty much what we've been saying. It's genetic in the way that heart disease is genetic, and not in the way that sickle cell anemia is genetic. The genes don't determine the disease - they make you susceptible, and the environment either pull the trigger or doesn't.

With that out of the way, the link has a fascinating discussion of a common genetic link to ancestors residing in England in the 1500s (50% of those tested had this link.) Of course, you'd have to look at the study to know whether or not this was interesting - if you only included people with the last names of Smithe and Brown, you'd sort of expect that they'd have lots of relatives in England.

My father's people actually came over on the Mayflower, so that's sort of interesting to me (although I sort of thought that they were Scottish and not English).

[hdugger]

For those who are more familiar with the Scoliscore research - are the people who score low on the scoliscore test similar to the general population? That is, are you ruling out progression in their case because they don't actually show a susceptibility to scoliosis? If so, what is it that caused their curve?

[hdugger]

Another way of predicting progression

Also from the Scoliscore site, they provide a link to an older article which gives the chance of progressing 5 - 10 degrees based on observable characteristics. Here's the formula:

(Cobb angle - 3 times Riser sign)/chronological age.

So, for my son, at diagnosis he had a 35 degree curve, I'm guessing a 4 Riser sign and was 16.

That's:

(35 - 3*4)/16 = 1.4

From the table (http://www.scoliscore.com/scoliscore...1984Study.aspx) that gives him a 30% chance of progressing.

Officially, I can't run his numbers, because the formula is only meant for curves between 20 and 29 degrees.

[Ballet Mom]

My daughter receives a score of 2.8 which shows 100% chance of progression. She didn't progress after bracing so I suppose that proves the brace worked, hmmm?

[Ballet Mom]

For those who are more familiar with the Scoliscore research - are the people who score low on the scoliscore test similar to the general population? That is, are you ruling out progression in their case because they don't actually show a susceptibility to scoliosis? If so, what is it that caused their curve?

Yes, I was thinking about that also. If the score of 0-10 is their lowest score, that must mean those are the people with the least genetic influence...and yet they still developed scoliosis and some of those develop a progressive curve. To me it shows the inaccuracy of what is being measured by the test.

[hdugger]

My daughter receives a score of 2.8 which shows 100% chance of progression. She didn't progress after bracing so I suppose that proves the brace worked, hmmm?

Wow, a 2.8! Twice my son's risk.

The predictive range of that computation is fairly narrow - it just shows if they'll progress 5 or 10 degrees, and not whether they'll progress all the way to surgical range. But, it does look like she had the odds stacked against her.

[hdugger]

To me it shows the inaccuracy of what is being measured by the test.

I suspect it's the environmental influence - sometimes you can stack the environmental triggers in such a way that even those who aren't susceptible succumb. Rickets is a good example of that - I don't think those kids have genetic susceptibility. They just have an environmental trigger.

Likewise, I think the great variability in the susceptible population shows an environmental influence. Kids all the way up to the top scores fail to progress. So, something in the environment went right for them.

[Ballet Mom]

Wow, a 2.8! Twice my son's risk.

The predictive range of that computation is fairly narrow - it just shows if they'll progress 5 or 10 degrees, and not whether they'll progress all the way to surgical range. But, it does look like she had the odds stacked against her.

Yes, she would have been at surgical range with just a five degree increase in Cobb angle. I know her surgeon believed she was going to go to surgery because he was telling us he wouldn't fuse her lower curve.

I actually think my daughter's risk was more than three times greater than your sons...i.e. 100% versus 30%.

[Ballet Mom]

I suspect it's the environmental influence - sometimes you can stack the environmental triggers in such a way that even those who aren't susceptible succumb. Rickets is a good example of that - I don't think those kids have genetic susceptibility. They just have an environmental trigger.

Likewise, I think the great variability in the susceptible population shows an environmental influence. Kids all the way up to the top scores fail to progress. So, something in the environment went right for them.

Agreed. I include in the error factor both the environmental aspect and the researchers perhaps not locating exactly every specific gene involved.

[hdugger]

I actually think my daughter's risk was more than three times greater than your sons...i.e. 100% versus 30%.

And I've had two cups of coffee already

You'd never know I was a statistics major.

[Ballet Mom]

And I've had two cups of coffee already

You'd never know I was a statistics major.

It's probably the coffee, lol.

[skevimc]

For those who are more familiar with the Scoliscore research - are the people who score low on the scoliscore test similar to the general population? That is, are you ruling out progression in their case because they don't actually show a susceptibility to scoliosis? If so, what is it that caused their curve?

They don't compare it to the general population. But they suggest in the discussion that it's very possible that many without scoliosis could possibly score high on the scoliscore. Or another way to look at it, it's not a test to assess scoliosis risk for the general population.

Also from the Scoliscore site, they provide a link to an older article which gives the chance of progressing 5 - 10 degrees based on observable characteristics. Here's the formula:


Officially, I can't run his numbers, because the formula is only meant for curves between 20 and 29 degrees.

That was the previous 'gold standard', if there ever was one, for progression risk. They compare the patients in their study that scored high (>180) to this formula and many of them had a low risk for progression. Yet they required surgery. The calculation can only be made with the strict criteria.

Yes, I was thinking about that also. If the score of 0-10 is their lowest score, that must mean those are the people with the least genetic influence...and yet they still developed scoliosis and some of those develop a progressive curve. To me it shows the inaccuracy of what is being measured by the test.

It's not inaccuracy because they aren't trying to pin point those who will develop scoliosis. They were able to identify, with >95% accuracy those patients who will progress to a surgical curve and with >98% accuracy those who would not. Your point is made about those curves could still progress to ~40*. And I agree with you. But don't fault the study or the researchers because it doesn't measure everything you wish it would. I've got a lot of things I'd like to see with their data as well but it was beyond the scope of what they were trying to do, i.e. identify those patients who would definitely progress to surgical range or not.



'Environment' most definitely plays a role. And in most patients that progress to surgery, genetics play a substantial role in the progression to surgery.

[hdugger]

They don't compare it to the general population. But they suggest in the discussion that it's very possible that many without scoliosis could possibly score high on the scoliscore. Or another way to look at it, it's not a test to assess scoliosis risk for the general population.

I sort of understand the people with the correct "genetic storm" who don't end up having scoliosis. I'm more unclear about people who don't have the genetic predisposition and yet still are diagnosed with scoliosis, even if they don't progress to surgery.

Is the idea that a smallish curve is unrelated to genetics, and that only larger curves are genetically based? Or are even those in the low risk group genetically different from the general population? That is, is there some hypothetical score below "0" which "normal" people have?

[hdugger]

Scoliscore and brace responsive patients

One thing I've wondered about the Scoliscore test is whether the low risk group are simply less likely to progress, or whether they're people in whom bracing is more effective. Conversely, are the high risk group people who just tend to progress, or are they people for whom bracing is ineffective.

I haven't seen this addressed on the Scoliscore site, but I do see Dr. Ogilvie (who did some of the research for the test) make a reference to it in an interview in 2007: "We anticipate that such a test will discriminate progressive curves from nonprogressive or brace-responsive curves"

If the test doesn't differentiate between non-progressive and brace-responsive curves in the low-risk group, how are they going to determine what treatment to use (or not use) in that group?