Advanced Maternal Age Associated with AIS?

[Elisa]

Yes, I think this is the great majority of people with scoliosis from what I've seen. Body type, hypermobility, and possibly in sports with repetitive motions over long periods of time in an intense way. It certainly seems to be a major factor in ballet and gymnastics and possibly swimming.

My 14 y/o son kinda (he looks pretty average for his age) has the body type, is not very flexible, doesn't do sports at all, no one we know in our immediate family has scoliosis and he's got this monster, super fast moving, relentless curve of 110*. He doesn't seem to fit the pic at all and that's so odd to me. What the heck happened to him!?

[Ballet Mom]

[QUOTE=Pooka1;116684]More conspiracy theories?[QUOTE]

I'd suggest you stop talking about conspiracy theories. It's not a conspiracy theory, it is what it is.

"AIS predictive test could eliminate inefficiencies
in the mild scoliosis group at great individual and
aggregate savings."

Paradigm shift described from bracing to no bracing and early fusion/fusionless surgeries with most cases of scoliosis not treated.

Ogilvie presentation http://www.vinzenzgruppe.at/vinzenzg...3Ogilivie.pdf/

Of course, "mild" scoliosis is all the way up to surgical levels. No skin off his nose.

[Ballet Mom]

My 14 y/o son kinda (he looks pretty average for his age) has the body type, is not very flexible, doesn't do sports at all, no one we know in our immediate family has scoliosis and he's got this monster, super fast moving, relentless curve of 110*. He doesn't seem to fit the pic at all and that's so odd to me. What the heck happened to him!?

That's why it's called idiopathic scoliosis. No one knows the cause. I'm sorry your son had that rapid progression.

[Ballet Mom]

I don't think there's any reason to doubt the Scoliscore researchers assertion that scoliosis is a multifactorial disease, like heart disease. The model they present, which I'm going to simplify as a greater or less genetic tendency to progress, makes sense of all of the different family stories I've seen on this forum.

For someone like Roher, it's possible that a very high tendency to progress (equivalent to a Scoliscore test above 180) is passed down. For any children with a high score, the environment would have to go really, really right for them to avoid progression. That still doesn't make the incidence or progression entirely genetic, it just says that the genetic stars are lined up in such a way that they're likely to progress. This might be equivalent to someone who has another multifactoral disease (heart disease) with an inherited tendency to produce a high level of bad cholesterol. My niece has this condition, and she has to be very, very careful with her diet just to stay healthy.

For someone who doesn't show a large number of relatives with scoliosis in their family, it's likely that they're passing down a lower score. They could progress, given a certain set of environmental conditions, or they could not progress, given another set of environmental conditions. This might be equivalent to someone with a less than optimal lifestyle who gets heart disease. The contribution in this case would be closer to half and half genetics and environment.

Finally, there might be someone with no relatives with scoliosis who is progressing entirely because of environmental factors with no genetic predisposition (equivalent to a low Scoliscore). It would take a huge amount of environmental push to tip them over the edge.

Unless we have people on the forum with entirely different etiologies - maybe Roher's family has some kind of connective tissue disorder rather than idiopathic scoliosis - no other explanation really makes sense of what we see on the forum. Yes, we see clusters of the disease in some families (indicating a high genetic influence) but we also see lots of cases without any clustering.

It's possible. It's also possible that what Scoliscore might be showing is simply the genetic influence of those initial Mormons studied. It could very well end up being accurate for those with familial scoliosis and not be accurate for those with a more environmentally initiated scoliosis.

It seems to me that familial idiopathic and juvenile idiopathic scoliosis are more closely genetically related than familial and non-familial AIS....they come from the same immediate families for the most part. And they may be the more difficult cases to treat...juvenile cases certainly are.

And I certainly agree with Dingo that there could very well be an trigger for the scoliosis even in the familial scoliosis. And how does Axial Biotech reconcile these studies that show maternal age seems to play a part...do they claim it's aging genes? I think they need to answer these questions.

I think Axial Biotech needs to address these issues much more specifically. I'm willing to donate my daughter's saliva to the cause if I can know the results, lol.

[hdugger]

It wouldn't need to be that straightforward. They might share a genetic susceptability to a particular strain of the flu virus that is common in the modern era. Scientists have no evidence that suggests what the initial triggering mechanism might be. The number of reasonable possibilities is practically endless.

I was focussing on progression, because that's where the genetic influence really seems to show up. As best I can make sense of the Scoliscore data, the initial *triggering* event is likely primarily environment.

[Ballet Mom]

Does anyone know if scoliosis cases that are known to run in the family (i.e. typically known as familial cases) have the tendency towards hypermobile joints?

[hdugger]

My 14 y/o son kinda (he looks pretty average for his age) has the body type, is not very flexible, doesn't do sports at all, no one we know in our immediate family has scoliosis and he's got this monster, super fast moving, relentless curve of 110*. He doesn't seem to fit the pic at all and that's so odd to me. What the heck happened to him!?

My surgeon suggested that they think boys have a different etiology from other patients. That's the reason he took an MRI. I've also heard that unusual cases (in this case, thoracic curves that go the "wrong" way) are often linked to neurological issues.

Not to suggest at all that your son has neurological issues (although I know my son has some), just to say that doctors regard scoliosis in males as something different from scoliosis in females. As a completely unscientific observation, for example, it seems to me that I see a much higher rate of Marfan's in men who post on scoliosis forums.

[rohrer01]

Yes, I think this is the great majority of people with scoliosis from what I've seen. Body type, hypermobility, and possibly in sports with repetitive motions over long periods of time in an intense way. It certainly seems to be a major factor in ballet and gymnastics and possibly swimming.

It seems to me that the sports that are mentioned here, gymnastics, swimming, and ballet (on another post) might attract people with a slender, flexible body type rather than the sport causing the scoliosis. This could certainly account for the higher number of people with scoliosis within their ranks.

[hdugger]

It seems to me that the sports that are mentioned here, gymnastics, swimming, and ballet (on another post) might attract people with a slender, flexible body type rather than the sport causing the scoliosis. This could certainly account for the higher number of people with scoliosis within their ranks.

Yes, that's true. But there was also a relationship, within those groups, between delays in the onset of menstruation and severity of curves.

[rohrer01]

I would think that delayed menarche would go more with the tall, flexible body type. The girls have more time to grow, thus more chance to progress.

[Pooka1]

Evidence driven directions in research

What a few researchers are working on in their own words. The players' names will be familiar. This is within the last few years but I can't find a date.

Note Moreau cites hormonal changes at puberty as an environmental factor. You have to speak the language to play the game.

http://www.aaos.org/news/bulletin/nov07/clinical3.asp

[Pooka1]

Gymnasts and Ballerinas - how researchers reconcile disparate findings

Journal of Dance Medicine (who know?)

Activities suggested to affect curve type but not severity which is incredible if true. I would love to see these data... I think it might approach field day proportions.

http://findarticles.com/p/articles/m.../ai_n28320815/

Studies in Health Technology and Informatics: "The NOTOM Hypothesis for Idiopathic Scoliosis: Is it Nullified by the Delayed Puberty of Female Rhythmic Gymnasts and Ballet Dancers with Scoliosis."

Journal of Dance Medicine & Science, Jan, 2005 by R.G. Burwell, P.H. Dangerfield

Burwell, R.G., and P.H. Dangerfield, "The NOTOM Hypothesis for Idiopathic Scoliosis: Is it Nullified by the Delayed Puberty of Female Rhythmic Gymnasts and Ballet Dancers with Scoliosis." Studies in Health Technology and Informatics 91:12-14, 2002.

It has been suggested that there are more girls than boys with progressive adolescent idiopathic scoliosis because of the different timing between skeletal maturation and postural maturation in the sexes during adolescence. We termed this concept the neuro-osseous timing of maturation (NOTOM) hypothesis, and used it to propose a possible medical treatment for idiopathic scoliosis by delaying puberty through the pituitary using gonadorelin analogues as in idiopathic precocious puberty. The prevalence of scoliosis is reported to be increased in rhythmic gymnasts (RGs) in Bulgaria and in ballet dancers (BDs) in the US. Both groups exhibit delayed puberty, which, at first sight, nullifies the NOTOM hypothesis for idiopathic scoliosis. While constitutional and environmental factors may determine these scolioses, the different curve types in RGs and BDs suggest that the exercise pattern over many years determines which type of scoliosis develops, although not the curve severity. The authors support the view that scoliotic RGs and BDs should be included in a group of sports-associated scoliosis separate from idiopathic scoliosis. Hence the delayed puberty of RGs and BDs with scoliosis does not nullify the NOTOM hypothesis, as their scolioses are not idiopathic. There is a need to focus research on such subjects, who have defined constitutional and environmental factors related to their scolioses.

[Pooka1]

How "genetic" is IS?

This whole article is relevant to this thread but I wanted to post the excerpt below to show how researchers decide how important genetics is to a disease.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2674301/

How “Genetic” is IS Compared to other Common and Complex Diseases?

Familial risk values may be used to estimate and compare the genetic effects across diseases. Prior sibling risk studies of IS have reported 19% and 11.5% of siblings affected for ≥ 10, ≥ 20-degree curves, respectively, compared to population recurrence risks of ≤ 2% [23, 33, 34]. In a cohort of 305 IS families we found 16% of siblings affected (unpublished data) and compared these numbers to the incidence of IS in the general population in order to estimate the sibling risk ratio (λs) for IS. This yielded overall λs values ranging from 8-23, dependent on curve severity. These values represent significant genetic effects that are comparable to those for other well-described complex genetic diseases such as rheumatoid arthritis (RA), Crohn’s disease (CD), type 1 diabetes (T1D), or psoriasis (Table 1). The possibility of a major gene contributing to IS, analogous to human leukocyte antigen (HLA) genes in the listed inflammatory diseases, has been suggested but remains unproven [39].

Also, elsewhere in the article, they equate "familial" with "dominantly inherited"

but also state:

The general consensus gathered from all of this is that, while families with dominant inheritance may exist, IS is generally a “complex” genetic disease that is not easily explained by existing inheritance models.

Also here is a claim about both the high frequency and the constancy of IS...

The relatively high frequency of IS (2-3%) in most (if not all populations) and its strong genetic underpinnings relative to other well-studied complex diseases predict good power for genome-wide studies [87].

And last, here is something on "familial" cases versus "sporadic" which really should be "apparently sporadic" since neither she nor any researcher radiographed all family members, living and dead, and therefore she can't know they are actually sporadic. This is not necessarily a peer reviewer problem because other researchers know this but the bunnies do not.

In any planned genetic study of IS it would seem rational to include familial cases of the disease. However, are such cases representative of the more common sporadic cases? As shown in Table 3, a comparison of sporadic cases to familial cases in one cohort revealed no significant differences in ethnicity, fraction of male probands, age at first presentation or severity in affected individuals (P>0.1 in all instances). Thus families with multiple cases of IS may provide important genetic information that is relevant to the more common sporadic IS patients.

[Pooka1]

And by the way, I did not realize that 1/4 to 1/3 of AIS is inherited in an identifiably autosomally dominant fashion. That is straight genetics or straight genentic susceptibility in the face of a ubiquitous environmental factor (maybe hormonal milieu or something that we know is definitely ubiquitous).

But the fact that these AIS cases that appear to be inherited in an autosomally dominant fashion do not differ from those inherited in more complex ways seems to suggest they are all one condition and either:

1. These "sporadic" cases are really all straight dominant inheritance (can't be ruled out unless you radiograph all living and dead relatives), or

2. All AIS cases are complex, polygenetic, and multifactorial (differential genetic penetrance, differential genetic heterogenicity, etc.) with a wide spectrum of patterns that extends to something that looks like straight autosomal dominance.

Or they could be two differnt conditions that happen to present identically. It would be hard to separate that out if that were true.

[Ballet Mom]

Journal of Dance Medicine (who know?)

Activities suggested to affect curve type but not severity which is incredible if true. I would love to see these data... I think it might approach field day proportions.

http://findarticles.com/p/articles/m.../ai_n28320815/

Ahhhh, now that's interesting!!! Thanks for posting that article.

They're saying that there's another category called exercise-induced scoliosis which would not be considered AIS. So obviously they wouldn't even be covered by the Scoliscore test....it's useless to them.

Very interesting, and should reflect on how the Scoliscore test is administered.

Scoliosis is multifactorial and should be treated as such.