EDS, hypermobility, and the link, if any, to ME/CFS

HEDS is very much real, myself and my children have it. It’s of my understanding, from talking to my rheumatologist and others with EDS or those fighting for diagnosis, it’s now a lot harder to be diagnosed as the criteria is so much stricter since the criteria changed for diagnosing EDS and JHS from 2017. I and my children were diagnosed under the new criteria.
 
The more I look at this the more it seems that the field is starting from a false presumption.

In the old days EDS consisted of a group of similar looking genetic conditions that early on were identified as Mendelian dominant from family histories. So it became accepted that EDS was Mendelian dominant. However, the grouping included EDSIII, which was a hyper mobility predominant type and at some point EDSIII got broadened by many physicians to be more or less synonymous with BHS. I don't think we have good evidence for hypermobility as a whole being Mendelian dominant. It cannot really be because it is so variable in degree and pattern.

It seems that recently an attempt was made to restrict the scope of EDSIII, or now hEDS, to people with Mendelian dominant inheritance and some evidence of other organ involvement. Or at least the requirement is for one first degree relative. A dominant pedigree might be more useful.

The situation is confused by including symptoms in the definition. This means that it is no longer an attempt to define an underlying causal process, but to define a clinical presentation.

But the question underneath all this is whether or not we have good evidence for one or more Mendelian dominant gene variants that are what criteria for hEDS are supposed to identify. If we do not know whether these genetic variants exist or how many then we cannot know whether the criteria over diagnose or under diagnose.

Criteria may define best practice in the sense of what is official but whether they define best practice in the sense of meaningful practice depends on the competence, as well as the honesty, of the people in the field. Unfortunately, my impression over the years is that many in this field do not understand the sort of complexities mentioned above.

Common genes may be difficult to find if the situation is polygenic and not Mendelian but I am pretty sure they are easier to find if they are Mendelian, simply because there will be lots more pedigrees to study.

I am not convinced that under diagnosis is more of an issue than over diagnosis here. I need to look into well defined cohorts and get some hard data. I am in the process of doing that.
 
Do we even know whether hypermobility with subluxations/dislocations is a single condition? Or indeed, whether it's a condition we're born with, or something we have a tendency to develop due to a pathological process?

It certainly runs in my family, but even after years of pondering, I'm still unclear whether it's even a single condition. For instance, in the last three generations, the majority of women on my maternal side have had unusually mobile joints. Some of us experience frequent painful subluxations in certain joints; in others, it's nothing more than a curiosity. So it's possible there could a general trait for mobile joints in the family, which only produces 'hEDS' symptoms when it's combined with unrelated skeletal abnormalities such as hip dysplasia.

In addition, some (many?) folk with regular subluxations have partners / friends / colleagues who learn how to shove the offending joints back into place. This takes the condition out of the realm of healthcare – so, despite decades of hip and shoulder subluxations, neither my late Mum or I were ever X-rayed to investigate the possibility of joint abnormalities, and you'd have to dig deep even to find mention of the problems in our GP records. If that sort of history is fairly widespread, it wouldn't be surprising if accurate data are lacking.
 
Kitty said:
Do we even know whether hypermobility with subluxations/dislocations is a single condition?
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I think that is the key question @Kitty.

For historical reasons a myth has grown up that there is a condition called EDSIII or hEDS but the evidence for that does not exist. There is no doubt that there are lots of people with mobile joints. There is also no doubt that some get recurrent strains. But as to whether 'EDS' has any real relation to ME I don't think we have reliable evidence.
 
After I was first diagnosed with EDSIII 6 years ago and began to look at the literature and saw that this was the only form of EDS for which the gene had not been identified, my first thought was to wonder how we know it was even the same disease. Indeed when I first read the constellation of symptoms several years before that, I remember thinking "you mean all those flukey things about my joints is, like, a thing?"

I meet all the criteria that @WillowJ posted above -- both the earlier and the later criteria -- and was diagnosed by a medical geneticist (though not genetically tested as my insurance does not cover genetic testing except in specific instances). Yet I've been puzzled about what is disabling about hEDS beyond frequent injuries (which I've had in abundance). I could still go to school in a cast boot or walking cast (back in the day when they were still made out of plaster). I had to be in the Special ED PE class because I was so prone to injury but my PE teacher was nice so that wasn't so bad. What has always been debilitating for me has been feeling like I have the flu all the time - i.e. PEM i.e. ME/CFS. On Facebook hEDS groups, most of the symptoms they are complaining about sound an awful lot like ME/CFS and I can't figure out why or how that would be related to hEDS. I see a lot of doctors in the EDS field suggesting all sorts of stuff but I've not seen any biological evidence of "stretchy blood vessels" or whatever.

That said, while I was always flexible and have had gut motility issues since birth, the frequency at which I've been experiencing joint instability has been getting progressively worse over the years (indeed my injuries didn't start until puberty). Most of that I have put down to muscle atrophy due to ME/CFS. Except the fingers in my hands are frankly dislocating at the drop of a hat (or rather, when trying to cut a steak or wrap a present) and my hands are probably the one part of me that still gets used fairly regularly. I don't type as much as I used to, or scrub the sink but I'm baffled by this and have begun to wonder if one of the sub-types of ME/CFS (or, if it turns out to be multiple diseases, one of the diseases that presents as ME/CFS) may indeed have some sort of soft tissue development.
 
Age 40. My GP was the one who wanted to refer me to the medical geneticist. As I mentioned, while I was I was always very flexible and had gut motility issues from infancy but it was only when I reached puberty that I began injuring. And not just soft tissue injuries (which were many) but multiple fractures as well.

Special Education Physical Ed. It was called "Adaptive PE" and was the class for students with various handicaps.
 
Trish said:
I am wondering how the medical geneticist diagnosed a genetic condition without a genetic test. Am I correct in guessing this was done on family history?
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EDS Type 3 is a clinical diagnosis. She was the only doctor in my area with any expertise in EDS so I was sent to her. While I have a niece who, like me, is 9/9 on the Beighton scale, she has never had any injuries and as a high school cheerleader, she's had more than ample opportunity. Otherwise, there is no history of anything like my symptoms on either side of my family that I've been able to discover.
 
Thanks, @Michelle. That's helpful.

I am trying to get my head around the different types of EDS, which I find very confusing.

I have just re-read Jonathan Edwards explanation in post #22 above, and now understand that EDS type 3 is not the Mendelian dominant type he describes at the beginning of his post, so family history may not be relevant.

Edited for clarity
 
Michelle said:
As I mentioned, while I was I was always very flexible and had gut motility issues from infancy but it was only when I reached puberty that I began injuring.
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I think this is fairly typical of people who get things like recurrent shoulder dislocation. Things start around puberty. I suspect that simply reflects the increased leverage on joints at the pubertal growth spurt. Younger children are a rounder shape and survive all sorts of forces. Hypermobility is also a developmental phenomenon - involving the relative rate of bone and ligament growth. Ligament development is in full swing from age 10-16. Interestingly the inflammatory ligament-related disorder (seronegative spondarthropathies) present from about 15-20, probably because this is around the time when growth stops (different at different sites) and the cell signalling rules change locally.

In theory nothing should get any laxer after age 25, unless joints wear down - which can make them wobbly. In theory pelvic ligaments elongate at their insertions under the influence of relaxin during pregnancy but the effect is not major and is temporary.
 
Am I right in assuming that levels of laxity of ligaments can run in families, even if it's not sufficient to label as JHS or EDS or whatever?

For example, I have very bendy fingers, including being able to flex the top joint while the rest are extended, as did my mother and my daughter, who also has lots of fairly lax joints from birth.

None of us has ever had a joint dislocation, so no medical intervention has been sought or needed, though she walked fairly late because her ankles were so lax her feet weren't flat on the floor. I did have that looked at (at UCH) and the doctor took one look at my bendy fingers and said that explained it and not to worry.
 
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Thank you to all who are contributing, v interesting.

My sister has an EDS III diagnosis (made in her mid forties) and reports what could sound like PEM. She has delayed onset fatigue, cognitive dysfunction and a general sense of not feeling well. We do debate whether we both have the same thing (I'm hypermobile, but wasn't diagnosed with hEDS when I saw a geneticist - he did say that someone else might decide differently)

@Trish My family shows hypermobility on both my parents' sides, also in all my siblings and all my children to varying degrees. As far as I know (don't know about more extended family) my sister is the only one diagnosed with hEDS.
 
As far as I know there is a spectrum of joint laxity without any clear indication that at any point it becomes a specific disorder. Just as being tall leads to bumping your head more often but there is no specific tallness disease. The definition of joint hypermobility syndrome was always arbitrary.

But there is no doubt that a very small number of people (~1/5000) have monogenic Mendelian dominant collagen gene abnormalities and they have not only severe laxity problems but problems in other systems. That is the basis of the concept of EDS.

What is unclear is whether we will ever work out the genetic basis of common forms of laxity or whether they are monogenic or, like height, polygenic.

But behind all this discussion is the issue of whether any form of joint laxity has anything to do with ME/CFS. We can expect 50,000-100,000 PWME in the US to have joint laxity just by chance. Maybe 10,000 will have sufficient laxity to run into sprains or dislocations, again by chance. About 200 will have documented Mendelian dominant EDS by chance (and 40 in the UK). And using Oxford criteria one could probably multiply that by ten.

I cannot see any mechanism by which genetic laxity should be linked to ME. That does not mean there is none but it would make much more sense if there is no actual causal link.
 
Jonathan Edwards said:
I think this is fairly typical of people who get things like recurrent shoulder dislocation. Things start around puberty. I suspect that simply reflects the increased leverage on joints at the pubertal growth spurt. Younger children are a rounder shape and survive all sorts of forces. Hypermobility is also a developmental phenomenon - involving the relative rate of bone and ligament growth. Ligament development is in full swing from age 10-16. Interestingly the inflammatory ligament-related disorder (seronegative spondarthropathies) present from about 15-20, probably because this is around the time when growth stops (different at different sites) and the cell signalling rules change locally.

In theory nothing should get any laxer after age 25, unless joints wear down - which can make them wobbly. In theory pelvic ligaments elongate at their insertions under the influence of relaxin during pregnancy but the effect is not major and is temporary.
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I actually stopped growing at age 11. The injuries started at 10. I grew one more inch between 10 and 11, when I peaked at 60 inches. The subluxations/dislocations all began after I stopped growing. Or at least, growing taller. ;)
 
Thank you, Jonathan. I think that put the picture very clearly. I have always assumed our joint laxity has nothing to do with our ME, and as you say, with 10% of the population having lax joints, there's statistically bound to be lots of pwME with lax joints as well.
 
Jonathan Edwards said:
I cannot see any mechanism by which genetic laxity should be linked to ME. That does not mean there is none but it would make much more sense if there is no actual causal link.
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I agree, I'm inclined to think it's a coincidence. Both joint laxity and ME occur in my maternal family; however, so does red hair, bradycardia, psoriasis/psoriatic arthritis, inherited neuropathies, and above-average height. It seems no more logical to link the ME with the hypermobility than it is with any of the others.
 
For what it's worth, all three of us affected by ME/CFS in my family are quite bendy.

We all score high on the Beighton index. I can fold my little finger over horizontally so that it pokes out the side of a fist, beside the thumb, and I've always been able to rest my knees flat on the floor when in the lotus position. My children have both had joint dislocations. My daughter was diagnosed with Osgood Schlatters disease and broke her ankle when playing football. My son recently had a wrist injury. Since developing ME/CFS, when I am tired I find that my legs will sometimes bend backwards at the knee when walking.

So, my personal experience leads me to not rule out a link between joint flexibility and ME/CFS, or at least orthostatic intolerance. But, who knows?
 
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