Hello Dr. Edwards,
Thank you for your input. I understand your concerns and recognize that this can be a vulnerable population, eager for hope, so I would like to address your concerns.
This theory was vetted with a huge expert in the EDS field before and after I wrote the Journal Article which was written for Medical Hypothesis (which explains the less scientific format). He was encouraging but involved in working on this in his own way within his area of expertise. I was unsuccessful in connecting with people who could prove it with a sophisticated genetics labs.
Since writing that article, many aspects of the theory have become more clear and evidence has presented itself in terms of patients sharing their personal histories with us and renowned experts contacting me and sharing the website. Right off the bat, I have received positive feedback from geneticists outside the US and since then many afflicted physicians who believe that this is correct. Two days ago, I was told by multiple people that one of the most prominent EDS experts has been sharing the theory with all of her contacts. Additionally, many known CYP21A2 carriers have also contacted me, sharing that all of the co-morbid conditions are scattered throughout their families and they are also sure I am correct, across the boards.
My significant other is an academic leader in internal medicine and because of my theory he sees patterns in his hospitalized patients and is able to predict family histories to the amazement of many of his patients. The compelling evidence is that many sick people show evidence of the kinds of findings in people with untreated congenital adrenal hyperplasia (untreated-because treatment with cortisol in infancy changes the presentation): gender fluidity, high intellect, PCOS/hormonal issues, tendency toward being left-handed/ambi, etc. etc..
I have found that the CAPS profile (psych profile involving sensory sensitivities, outside of the box thinking, perfectionism, etc) which can be explained by abnormal hormonal exposures in infancy (including the larger than normal amygdala found in EDS) and evidence of androgenization in women can predict MCAS and chronic psychiatric and medical illness clinically (anecdotally).
I disagree with you on several points. The EDS population is rife with CFS/ME and the huge number of symptoms are exactly the same. Spending time on forums for all of these conditions makes it clear. Living with decompensated EDS, POTS, MCAS, CFS really makes it clear. As discussed above, decreased tenascin or tenascin insufficiency is a rare cause of EDS, but abnormal tenascin X due to TNXB mutations is rampant (as evidenced by the high rate of calcific aortic valves and vesicoureteral reflux and high percentage of people with those very recently being found to have abnormal-not deficient in quantity-tenascin and some hypermobility).
Karen Herbst MD PhD is an internationally recognized expert in subcutaneous adipose disorders and has or will be publishing soon the high rate of hypermobility in these disorders. CFS is known to be associated with Dercum's. She sees this CAPS profile in a high number of her patients. As mentioned above, the CAPS profile is one of the markers I have found.
Further, everything on the list can be explained by these mutations. TNXB: varying degrees of hypermobility, high TGF beta likely explaining the high rate of endometriosis, fibrotic issues,likely contributes to dysautonomia due to lax vessels, musculoskeletal injuries due to tissue weakness in some; CYP21A2: stress vulnerability as this codes for the key enzyme in the acute stress response, CAPS, see pathophysio diagrams for POTS, MCAS, Adrenal fatigue, raised ICP, hormonal issues, exaggerated stress response before sick, crashing and body and brain inflammation via high CRH afterward 21 hydroxylase overwhelmed.
The acute stress response is very much tied to inflammatory conditions-look at what people with PTSD get (very similar to us). C4: associated with MS, autoimmune diseases, now schizophrenia, etc. It has been shown that these genes travel together very frequently in the literature, causing conditions like EDS and CAH to co-occur at a much higher rate than by chance. C4 has been shown to run with CYP21A2 at a high rate as well.
The donations to the RCCX Project are for research looking into the RCCX module's role in chronic illness, not specifically for Karen and I. If someone came along and had the facilities to do a large scale study on the RCCX, the funds would go there (for example someone like Ron Davis PhD). Karen and I have unique expertise to look at the clinical aspects of CYP21A2, including CAPS and the hormonal derangements and I believe we would be a very valuable asset to any study looking at this.
We may even have to hire a top RCCX genetics expert for our samples if the University of AZ lab is inadequate and we are testing the lab right now with CAPS patients and will have our lab fully vetted before we use our donations to pay for the testing. Karen is paid by the university to do research and will not use the donations for any of her work. I am volunteering my time at significant cost to my personal life and health because I so strongly believe in this cause. If our genetics lab is inadequate and we don't have the money to hire an expert, we will return the funds we receive, minus the lawyer fee for setting up the nonprofit.
I think that the evidence and the website speaks for itself. I am not able to put too much effort into arguing these points (due to my own health), which is why I put it all out on the website and did not take the conventional approach which would have involved writing and rewriting this. I surely would have ended up disabled, as my level of illness directly correlates with my level of stress (goes with the theory).
It took a lot of thought before I released the website. The last thing I wanted to do was to become a public figure and I already have a 6 month waiting list for my practice which is not directed toward treating chronic illness. I had no intention of being involved in the research effort when I first posted the website for a test run (which involved 13000 views in a week and an outpouring of support). With this response from the EDS community and beyond and Karen contacting me, it was clear that we had the skills to greatly contribute to this effort. It's a grass roots effort. If I am right, looking at the RCCX could save years in studies trying to work backwards from downstream derangements, and there can be some directed treatments developed for us, rather than outrageously expensive immunological drugs which I believe try to block downstream issues.
As I know that the CAPS psych profile (smart, good at seeing patterns as part of it) is high in this community, I know that people in this community will take a look at the theory and decide for themselves whether they or their family medical histories could be explained by mutations of these genes co-segregating. I f they believe in it, they know where to find us (above).
I'm here for questions, but I'm heading into my work week and need some time to decompress before then