Scoliosis in the context of human evolution

[mamamax]

I know what I'm going to say is possibly the most simplistic thing I've ever said (apologies in advance).

I'm beginning to develop a sense that sometimes IS may be genetic in origin (regarding a predisposition) - and sometimes it is not. Sometimes the predisposition is triggered, and sometimes not.

And being that the greatest minds cannot figure it out, the term idiopathic becomes the title of the equation. Some great minds say the title should be changed to familiar scoliosis vs genetic.

At this point, I'm thinking hdugger has probably said it best:

I'd call AIS, like most other disorders, non-genetic, except in those few cases where it can be traced specifically to genes. Otherwise, like every other disorder, it's a genetic predisposition coupled with environmental factors. In usual parlance, that's not called a genetic disorder.

[Pooka1]

hdugger calls IS non-genetic whereas all the researchers to my knowledge ACCEPT that genetics is strongly involved based on the technical reasons in that paper. So there's that.

Also, common parlance is not relevant here. It either has or has not been shown that there is a strong genetic component to idiopathic scoliosis. Per the literature, is HAS been shown. That doesn't mean it is correct but it is certainly PROVISIONALLY correct at this time. And it also means that if someone wants to question it then they need to pony up some evidence. That hasn't occurred. So the claim still stands on the evidence FOR a strong genetic component.

There appears to be no basis at this point to suggest idiopathic scoliosis is likely caused entirely by an environmental trigger alone or even that that is the dominant driver given the data in that paper and at large.

All these threads on this topic hinge on lay equivocations of scientific terms coupled with an unfamiliarity with the literature as far as I can tell.

[Dingo]

idiopathic

I've read more than my share of abstracts and in my opinion certain children probably do share some type of genetic susceptibility to Scoliosis.

However scientists haven't been able to determine the cause of Scoliosis. Until they do it's idiopathic.

I should add that almost every disease has a genetic component. The fact that scientists may eventually associate Scoliosis with a particular set of genes might not mean very much.

Exhibit A
Scientists pinpoint flu gene

An unlucky combination of "vulnerable" genes could explain why some people recover from the flu overnight and others struggle to shake off the virus for weeks.

It goes without saying that "the flu" is not a genetic disease.

[Pooka1]

However scientists haven't been able to determine the cause of Scoliosis. Until they do it's idiopathic.

But that's not how these researchers use the term. They accept that genetics is involved while still referring to it as IDIOPATHIC in the same breath. Look at this quote...

The recognition of genetic influences in IS is well-documented [19-25].

Clearly, they are using idiopathic to denote that WITHIN a genetic framework, they still don't know the etiology. So it is still idiopathic. Clearly the term "idiopathic" does not rule out genetic or they wouldn't constantly using that construction.

This is their field and they get to define these terms. The only conclusion possible at this point is that there is nothing contradictory about claiming idiopathic scoliosis has a strong genetic component while still being idiopathic.

If you have literature that contradicts any of this I would like to read it.

[Dingo]

Brazilian study

The genetics of Scoliosis is still controversial. Nobody has been able to prove beyond doubt which genes are involved or how they might contribute to Scoliosis. I suspect that genes may create some type of susceptability but that's a far cry from having scientific proof. Right now we simply don't know.

2010: Genetic aspects of adolescent idiopathic scoliosis in a family with multiple affected members: a research article

Evaluation of 57 family members, distributed over 4 generations of a Brazilian family, with 9 carriers of adolescent idiopathic scoliosis. The proband presented a scoliotic curve of 75 degrees, as determined by the Cobb method. Genomic DNA from family members was genotyped.

While it was not possible to determine a chromosome region responsible for adolescent idiopathic scoliosis by investigation of genetic linkage using microsatellites markers during analysis of four generations of a Brazilian family with multiple affected members, analysis including other types of genomic variations, like single nucleotide polymorphisms (SNPs) could contribute to the continuity of this study.

[Pooka1]

What you posted does not in any way undermine the claim that idiopathic scoliosis has a strong genetic component. The genetic component can and has been shown ahead of finding the DNA regions involved although Ogilvie thinks he has the gene suite identified. The fact that he has produced that graph and that it is predictive is a strong argument that steals the ground from anyone claiming genetics is not strongly implicated in idiopathic scoliosis. And that is not even among the evidences cited in that 2008 paper for a strong genetic component to idiopathic scoliosis as I recall.

That genetics is a strong component to idiopathic scoliosis is not controversial. Can you post a paper that claims it is?

[mamamax]

Understanding Genetic Factors

The genetics of Scoliosis is still controversial. Nobody has been able to prove beyond doubt which genes are involved or how they might contribute to Scoliosis. I suspect that genes may create some type of susceptability but that's a far cry from having scientific proof. Right now we simply don't know.

2010: Genetic aspects of adolescent idiopathic scoliosis in a family with multiple affected members: a research article

I would agree that the genetics is controversial in that there is much "argument" about it in the literature. Susceptibility is a word emerging in the literature that certainly gives cause to pause.

It would seem, that today - the hunt is for: susceptibility genes and disease modifiers.

Understanding Genetic Factors in Idiopathic Scoliosis, a Complex Disease of Childhood Carol A Wise,1,2,3* Xiaochong Gao,1 Scott Shoemaker,4 Derek Gordon,5 and John A Herring2,6 (2008).

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

From the Abstract:

Despite many investigations, the underlying etiology of IS is poorly understood. Twin studies and observations of familial aggregation reveal significant genetic contributions to IS. Several features of the disease including potentially strong genetic effects, the early onset of disease, and standardized diagnostic criteria make IS ideal for genomic approaches to finding risk factors. Here we comprehensively review the genetic contributions to IS and compare those findings to other well-described complex diseases such as Crohn’s disease, type 1 diabetes, psoriasis, and rheumatoid arthritis. We also summarize candidate gene studies and evaluate them in the context of possible disease aetiology. Finally, we provide study designs that apply emerging genomic technologies to this disease. Existing genetic data provide testable hypotheses regarding IS etiology, and also provide proof of principle for applying high-density genome-wide methods to finding susceptibility genes and disease modifiers.

[livingtwisted]

I'm not really interested in getting into the middle of a semantics debate, but I have to ask...

Pooka, I understand and accept that genetics have been determined to play a role in some idiopathic scoliosis cases. But are you suggesting that genetics is always one of the factors causing every idiopathic case? Isn't it possible that there are more types of scoliosis than have been classified yet, each with different causes?

Right now scoliosis is considered to be multifactorial, but I wasn't aware that every possible factor was present in every case. Unless I am mistaken, that would lead me to think that genetics is a factor, but to call scoliosis a genetic disease would be misleading.

facts are facts, but they need context.

[mamamax]

The "genetic" frontier

Here is a very interesting Q/A session with: James W. Ogilvie, MD, past president of the Scoliosis Research Society; Nancy H. Miller, MD, orthopaedic surgeon/scientist at The Children’s Hospital in Denver, and a consultant to the department of orthopaedic surgery at Johns Hopkins University; Alain Moreau, PhD, director of the bone molecular genetics and skeletal malformations laboratories at the Ste-Justine University Hospital Centre, Montréal, Canada; and Carol Wise, PhD, director of molecular genetics at Texas Scottish Rite Hospital for Children.

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

A comments by Ogilvie and Moreau, certainly captured my attention!

Dr. Ogilvie: Years ago, ulcers required surgery; now, they’re treated with a pill. Ulcers have become a medical—not a surgical—disease. I anticipate that the research on scoliosis will result in favorable nonsurgical outcomes as well.

Dr. Moreau: Most likely, scoliosis is not a purely genetic disease. Although genetic factors are important, a “cross talk” between genetics and some environmental factors is evident. The nature of these environmental factors, however, is unclear. The underlying genetic defects may be present at birth, but because the clinical manifestations usually occur at adolescence or prepubescence, scoliotic deformities must be triggered by environmental factors, which also include hormonal changes associated with puberty.

Increased levels of estrogen at puberty could explain why girls are more affected in number and severity than boys. Blood tests can now identify children at risk of developing scoliosis. We need to do more work on phenotype and trying to make sense of that and correlating it to genotype.

[Pooka1]

Pooka, I understand and accept that genetics have been determined to play a role in some idiopathic scoliosis cases. But are you suggesting that genetics is always one of the factors causing every idiopathic case?

I am not personally suggesting anything as this is not my field. I am reporting what the literature holds on this point. It either does or does not hold certain claims. That's all I'm saying.

Beyond that, my understanding of the literature is that all idiopathic scoliosis has a strong genetic component as far as has been shown. That is not to say that JIS can't have a different suite of genes involved compared to AIS.

I haven't seen anyone post a single thing, nor have I come across a single paper that contradicts that. I am open to someone posting something in contradiction if it exists because I am always open to anything in contradiction of anything. That's what it means to approach a subject in an intellectually honest manner.

Isn't it possible that there are more types of scoliosis than have been classified yet, each with different causes?

I don't know if that is possible as this is not my area. I can only read the literature. I am just saying that it is ACCEPTED by the research community that idiopathic scoliosis has a strong genetic component. I have encountered nothing yet in opposition to that. Please feel free to post something that disagrees with that.

Right now scoliosis is considered to be multifactorial, but I wasn't aware that every possible factor was present in every case. Unless I am mistaken, that would lead me to think that genetics is a factor, but to call scoliosis a genetic disease would be misleading.

Nobody to my knowledge called idiopathic scoliosis a genetic disease. Look at the wording used in the review article. The claim appears to be it has a strong and identifiable genetic component, not that it is a genetic disease. These are terms of art and it is important to use them correctly.

[Dingo]

idiopathic

Mamamax

It would seem, that today - the hunt is for: susceptibility genes and disease modifiers.

Bingo! You nailed it.

BTW good studies as always!

In all likelihood the cause is multifactorial which puts Scoliosis in the same category as almost every other disease that mankind has studied.... including the flu.

genetic susceptability + environmental damage = disease

[hdugger]

It's the terminology I'm trying to clarify. A genetic predisposition is not what people generally understand to be a genetic disease.

So, I have a genetic predisposition to weak teeth enamel, which my son has inherited (or, so I assume - I haven't actually researched this). My husband, OTOH, has tooth enamel like steel, which my son did not inherit.

But, noone talks about the etiology of cavities as being genes. The etiology is all about substances that eat through enamel. Scoliosis *appears* to be similar, in that's it's largely related to a certain body type, which is accepted as an inherited characteristic. But that doesn't mean that the body type (or whatever the underlying genetic factor is) *causes* the scoliosis. It just means that having a certain set of genes predisposes you to be more affected by certain environmental conditions.

*Everything* is in some way affected by genetic predispositions. I mean, you could do a twin study on basketball playing and find that it seemed to run in families (and be oddly related to stature ), but that doesn't mean that genes cause basketball playing. It means that they lay the groundwork for everything that we do/are/enjoy/suffer from.

If genes play a larger role than that in scoliosis, I haven't heard it from the medical community. That is, I haven't heard that they play a role is the *specific* etiology - for example, I haven't heard that the genes "fire off" at a certain age and begin to wedge the vertebra. All I've heard is that they predispose, but noone knows the actual cause.

[Dingo]

Genes and AIS

hdugger

If genes play a larger role than that in scoliosis, I haven't heard it from the medical community. That is, I haven't heard that they play a role is the *specific* etiology - for example, I haven't heard that the genes "fire off" at a certain age and begin to wedge the vertebra. All I've heard is that they predispose, but noone knows the actual cause.

You hit on an important point. Even if genes are involved nobody is suggesting that these genes program the spine to grow deformed.

These genes could create susceptability in a myriad of different ways.
A) A gene might increase the susceptability to a particular strain of the flu virus that triggers Scoliosis by damaging part of the brain or nervous system.
B) A gene might create a susceptability to pollution and allergies that leads to inflammation which in some children leads to Scoliosis.

The possibilites are limitless.

Type 1 Diabetes appears to have a genetic component but that doesn't mean the body is preprogrammed to destroy it's own B-cells at a particular age.

Study Of Human Pancreases Links Virus To Cause Of Type 1 Diabetes

[Pooka1]

It's the terminology I'm trying to clarify. A genetic predisposition is not what people generally understand to be a genetic disease.

What is the proof there is only a genetic predisposition with IS? Researchers have suggested that but it seems like the main evidence for the conjecture is a lack of a clear genetic inheritance pattern. So they have to make room for that possibility but complex inheritance patterns which may appear to be multifactorial can be straight genetics... here's a quote that appears to be alluding to this from the Brazilian study Dingo posted...

Hereditary factors can also determine the etiology of the disease; however, the pattern of inheritance remains unknown. Autosomal dominant, X-linked and multifactorial patterns of inheritances have been reported [1-3,5-8]. Segregation analysis has suggested a single gene as major determinant of idiopathic scoliosis in patients with curves equal to or greater than 11° (Axenovich et al. 1999). Other studies have suggested possible chromosome regions related to the etiology of idiopathic scoliosis, including a genetic locus for adolescent idiopathic scoliosis linked to chromosome 19p13.3., considering affected members as those individuals with curves greater than 10°, without reference to the presence of consanguinity [1,3,7-9].

If genes play a larger role than that in scoliosis, I haven't heard it from the medical community. That is, I haven't heard that they play a role is the *specific* etiology - for example, I haven't heard that the genes "fire off" at a certain age and begin to wedge the vertebra. All I've heard is that they predispose, but noone knows the actual cause.

Here is the first line of the Results section:

Evaluation of familial history of the individuals studied revealed an autosomal dominant pattern of transmission (Figures 1 and 2), with 9 affected members, 12 unaffected members and 36 members showing some characteristics of the disease, classified as suggestive of idiopathic scoliosis.

So if there is an environmental trigger, it has to be ubiquitous to look exactly like straight autosomal dominance in that family at least.

Straight genetic control has not been disproven to my knowledge. Nor has a multifactorial etiology with some environmental trigger. Nobody has shown that IS genetics is definitely a case of susceptibility to my knowledge. If you have a citation otherwise please post.

Also, read that paper I posted about hte evidence for a strong genetic component.

The reason this exchange started is the claim that it is possible that IS may not have a genetic component. That has been disproven with the evidence in hand.

[Elisa]

I am way out of my league here, but has anyone ever considered that IS 'might' be an autoimmune disease? With my son it seemed to come on so suddenly and has progressed quite rapidly. We really only noticed his back was off close to a year ago and look at the shape of his spine now. His curve(s) is very significant.

When older son was almost fourteen he was diagnosed with HSP (Henoch–Schönlein purpura) http://en.wikipedia.org/wiki/Henoch%...6nlein_purpura which is an autoimmune disease which they think might be triggered by such things as: exposure to cold weather, a bug bite or perhaps a reaction to a vaccination. At the time when my son became ill, he had gone on a ski trip with his class and got very cold as well as he had recently received a vaccination at school.

Is it possible that IS could be an autoimmune disease?