Hypermobility, RCCX Theory and One Journey From Illness Towards Wholeness

by Courtney Snyder, MD

The human body is a mystery.  As much and as fast as we’re learning, we still know very little.  This post is about a recent discovery.  I call it a “discovery,” because I’ve lived out what this theory holds to be true, as have a number of patients I work with, and perhaps some of you reading this.  RCCX theory is quite complex.  The best I can do is share my personal experience with the hope that doing so will help make this information more accessible.

We all have traits that make us different - whether it’s our appearance, how we react to our world or the natural abilities we possess.  Some traits, we may take pride in, others not so much.  Ask me why I’m flexible and I’ll tell you I did gymnastics when I was young.  Why do I have low blood pressure? I exercise regularly.  My flat feet?  Just one of those genetic things.

​As a child I worried...a lot.  In my second year of college, I could have been diagnosed with depression.  I’m the kind of person who can’t watch Cirque du Soleil without turning away for fear I’ll witness someone plunge to their death.
 
Never had I imagined each of these traits could be related, or that they would foreshadow a ten year health struggle that I’m only recently coming out of.

I was 37 when my health problems began. Recurrent “urinary tract infections” came first - then recurrent sinus infections and with these recurrent antibiotics.  Infertility led to a diagnosis of ovarian cysts and endometriosis. The cesarean section birth of our daughter was quickly followed by a reaction to a pain medication, then a reaction to the medication for the reaction to the pain medication before a raging cellulitis/skin infection on my abdomen. There was the mild chest pain and tingling sensation in my left arm that led to an extensive cardiac workup. Next, came subtle difficulties using my fingers and hands.  More dramatic neurological symptoms came after 2 courses of antibiotics - leg weakness, changes in vision, severe headaches, nausea related to the position of my head, which at times required effort to hold up, and episodes of heightened anxiety and racing heart. Later, it was swelling in my legs and “air hunger” - the feeling that you can’t get a deep enough breath. Sprinkled throughout was intermittent brain fog, which for me meant difficulty finding words, problems with driving directions, problems retaining what I’d read or heard and at times forgetting what exactly what it was I was doing. Often present - a blanket of fatigue  - an invisible resistance that made even drying my hair a challenge.  Much of this couldn’t be validated with typical labs and imaging.  To all but my husband and daughter, I didn’t appear “sick.” Respite came in the form of long (at times 3 hour) naps that would have been blissful but for my pounding and irregular heart beat.  

Trying to understand complex chronic health issues for myself and my daughter during ten years away from psychiatry and medicine, led me to functional and holistic medicine.  Everything I learned helped us and helped me help others when I did return to practice. Unfortunately and fortunately, there was always more to be unraveled.  The gastrointestinal candida/yeast overgrowth led me to the micro-biome which led me to nutrient imbalances (elevated copper, low zinc, methyl/folate imbalance, pyrrole disorder, etc.), which led me to bio-toxicity (in my case, mold toxicity), which led me to mast cell activation….which led me to things I had that I didn’t even know there was a name for.  Each step moved me closer to health, but none could explain why instead of just one or two or even three of these, I had them all.  This was also true for a handful of patients coming to my office for help.

Occam's razor is a problem-solving principle attributed to William of Ockaham (c. 1287–1347), an English Franciscan friar, philosopher, and theologian. His principle basically says - “Among competing hypotheses, the one with the fewest assumptions should be selected.”

How could so many problems be distilled down into one unifying theory? 

“Do you have a history of trauma?”  an internist once asked me after hearing my symptoms.  My cholesterol in the 400’s and my abnormal neurologic exam made it difficult to chalk this all up to being “in my head.”  I realized he must be referring to the landmark ACE study, which links childhood adverse events with adult chronic physical and psychiatric conditions.   “I suppose it depends on what you consider traumatic,” I responded...For me, sitting through the first 20 minutes of “Bat Man Returns,” was trauma.

I thought to myself, "I’ve been lucky.  I’ve not been neglected, nor physically, emotionally or sexually abused.  I did not have a time in my early childhood when I was separated from my parents who by all accounts loved and wanted me and my brothers and sister.  I was never bullied.  There was no trauma in the obvious sense of the word."
 
If not childhood adversity, then could there be another unifying theme for what at times felt like the seven plagues? Maybe the universe wanted me to learn intimately….about ALL of these conditions... so I could help others.  At least that would bring some purpose, some reason. 

***

The recognition that I fell on the hypermobility spectrum came only recently. I began noticing a number of health issues I'd struggled with, namely MCAS/Mast Cell Activation Syndrome and POTS (Postural Orthostatic Tachycardia Syndrome) also occurs in people with Ehlers Danlos (ED) - a group of genetic connective tissues disorders which can result in loose joints, stretchy skin and abnormal scar formation.  I am flexible (which is likely why I gravitated to gymnastics).  Though I don’t have Ehlers Danlos, I do fall on that spectrum, meaning I likely have an affected gene, but not affected enough to warrant that diagnosis.

MCAS/Mast Cell Activation Syndrome - again, very common in people on the hypermobility spectrum - results when mast cells release a range of immune mediators including high levels of histamine.  The result can be wide range of hard to diagnose symptoms throughout the body including migraines, diarrhea, sinus pain, burning eyes, syncope/fainting, distractibility, brain fog, irritability, interstitial cystitis (feeling like you have a urinary tract infection when you don’t actually) to name just of few. It looks different in different people.  If you know anyone who seems to react to “everything” they may have a mast cell problem.

POTS/Postural Orthostatic Tachycardia Syndrome  is a condition in which a change in position from lying down to upright results in increased heart rate.  Symptoms can include palpitations, lightheadedness, nausea, heaviness in lower legs, blurred vision or cognitive problems (due to decrease in blood flow to the brain).   Such symptoms can get worse with prolonged sitting, standing, alcohol, heat, exercise or eating a large meal. 

Many people with MCAS and/or POTS are diagnosed with Chronic Fatigue Syndrome, also called Myalgic Encephalomyelitis, and/or Fibromyalgia as I would’ve been, had I persisted on the conventional/allopathic path. 

***

Each time I thought I was improving, I would be humbled by a severe headache, or overwhelming fatigue. Over years (literally years), I learned this was a battle I couldn’t win,  in part because it was at battle with myself.  

Instead of fighting, I simplified - removed everything that didn’t matter to me. I'd lost energy for and could no longer tolerate TV, stuff, ego driven aspirations…. I let go of relationships and activities that were no longer meaningful for me.  By necessity, I made my life simple and closer to what nature had intended.

Too, I realized my excessive focus on my health, was reinforcing a belief that I had total control over the outcome. Instead of putting my remaining energy into trying to further fix my biochemistry,  I started to grow a spiritual life - through writing and eventually reading books by spiritual writers. I learned to trust and listen to myself.  This brought moments of peace I couldn’t find in functional medicine forums or illness related facebook groups.  

Two weeks ago, while enjoying a whimsical book, the author charged me to ask (and expect) the universe to deliver a gift...within 48 hours.  The universe was to respond, “My pleasure.”   Not wanting much in the material sense, I was curious, what (if anything), I might receive.  After all I’ve described above, you’d think I’d have something to ask for...I didn’t...I’d mostly stopped looking and stopped grasping.  I was relatively at peace.

Within one hour of my request, I happened upon the work of Dr. Sharon Meglathery and her RCCX theory. There it was - my gift.  Brilliant.  It was all right there and in many ways, my story was all right there. 

Dr. Meglathery is a psychiatrist and internist with a health history very similar to my own.   Her theory explains a great deal for the many of us with both hyper-mobility (or with a family member with hyper-mobility) and an unusual mix of chronic health issues.  While I pride myself in my ability to connect the dots, here was someone who’s harnessed this ability tenfold.  We spoke at length by phone.  Aside from her obvious intellect, she’s remarkable in her generosity of spirit and sense of moral responsibility to get this information “out there”.

According to her theory, the “co-inheritance of a cluster of highly mutable genes,” collectively referred to as RCCX, “may confer vulnerability to familial clusters of overlapping syndromes of chronic illness (hyper-mobility, autoimmune disease, Chronic Fatigue, MCAS, POTS, and psychiatric illness, etc.).” Basically there’s a cluster of genes that are inherited together, they each can mutate easily and because they're big players, if they do have a mutation, they can make people vulnerable to wide range conditions and symptoms.

That these genes are inherited as a block as opposed to being inherited separately, doesn’t mean a mutation in one causes a mutation in all.  There does, however, seem to be a high rate of co-inheritance of mutations in two of the genes - the gene that relates to hypermobility and the gene that relates to an impaired hormonal stress response that can result in chronic physical or mental illness in large part due to the mast cell activation it causes. 

This makes hyper-mobility an especially important marker for physicians and other practitioners to consider when meeting anyone seeking help for chronic medical or psychiatric conditions.  This seemingly unrelated trait, can be big clue as to what's going on.

And for those who are not ill, hypermobility may suggest a vulnerability to becoming ill (physically and/or mentally) after acute or chronic stress.

While the conditions (described below) can occur in one person and/or sporadically throughout families with this RCCX gene cluster, women are usually impacted the most.  One person (ie. myself and Dr. Meglathery) in a family can seemingly be hit the hardest or at least with the physical aspects.  Brain related symptoms can predominate for many.

The genes (oversimplified):

(1) TNXB  - codes for tenascin, a protein involved in collagen architecture.  A mutation here could cause hyper-mobility to varying degrees (from none to Ehlers Danlos).   The integrity of our connective tissue is also important for our gastrointestinal lining, our blood vessels, our gut blood barrier and blood brain barrier.  Loose connective tissue can also impact us by way of upper cervical (neck) instability which can impact the vagus nerve, which has an important role in preventing brain related symptoms and inflammation. 

(2) CYP21A2 - codes for an enzyme, 21-hydroxylase which is pivotal in hormonal pathways involving progesterone, and less directly androgens.  A mutation here is associated with an “exaggerated stress response in the setting of low basal cortisol." This is best described as “tired but wired.” Seemingly, only one copy of this gene (meaning from one parent) is necessary for someone to be vulnerable to medical or psychiatric illness after severe acute or prolonged stress.  

(3) C4 - codes for complement C4 - a protein involved in the immune response.  A mutation here could result in autoimmunity - the immune system overreacting and essentially becoming destructive to specific areas/functions of the body such as in Type 1 diabetes, multiple sclerosis and rheumatoid arthritis, to name a few. 
 
“I posit that a child carrying a CYP21A2 mutation has the same brain as a child raised in adverse circumstances,” says Dr. Meglathery before describing the structural differences in the brain including enlarged limbic structures (amygdala).

In utero and infancy, the brain (of someone with a CYP21A2 gene mutation) is exposed to low basal and spiking cortisol levels which leads to a brain that is essentially wired for danger, not unlike the brain of someone with PTSD.  Decreased cortisol levels result in the brain releasing ACTH (Adrenocorticotropic hormone) and CRH (Corticotropin-releasing factor) - a hormone involved in the stress response.  When stress is too high or too chronic, the pathway is overwhelmed and brain inflammation occurs.

This decreased ability to deal with stress (and thus propensity to inflammation), according to Dr. Meglathery, “raises one’s susceptibility to PTSD/Post Traumatic Stress Disorder  or other forms of disordered emotional processing.”  The overwhelm of this 21-hydroxylase (the enzyme that’s not working up to speed) can trigger an inflammatory cascade resulting in  all of the conditions mentioned above ie. MCAS, POTS, CFS/ME, (as well as chronic inflammatory and/or biotoxin illness as is seen in Lyme Disease, Mold Toxicity, Epstein Barr Infections, etc.).  Associated psychiatric issues cover the full range from anxiety, panic, OCD, depression, bipolar disorder, ADD/Attention Deficit Disorder, hyper-focus, autism, sensory processing, and psychosis. 

RCCX Theory will likely change the way we think about chronic physical and mental illness.

***

While I’ve worked with many children and adults with early trauma and disrupted attachment, I’ve also worked with many who didn’t have this (known) history, but seemed wired as if they had.  Some were told by therapists they must have had trauma they couldn’t recall.  Some even decided they were abused as a way to make sense of their heightened sensitivity and stress response.

At the “expense of emotional processing and possible psychiatric illness,” Dr. Meglathery describes a potential for "brilliance and high intellectual capacity.”  She says, “With increased threat detection and enhanced stress response, if present in moderation, comes some gifts, including enhanced empathy, ability to hyper-focus/obsessions/special interests and unusual abilities (often in music, arts or abstract thinking).” 

I’m not the only person in my family with some seeming “out of blue” abilities.  And while I’ve claimed few of these, I’ve quietly wondered how it is that I was able to write music and make art without formal training. And, yes, at times in a hyper-focused and obsessive manner. 

Also striking is the uncanny tendency for those with the RCCX phenotype to marry or have friendships with others on the RCCX spectrum.  If you are someone who falls on this spectrum, your relationships will likely confirm this.

***

But is this theory worth knowing?… Is it fatalistic, self-indulgent, or is there something of use here?  Is there a reason to share this information...not in 25 years when this gets fleshed out by geneticists, but right now? 
 
I’ve had tremendous benefit from dietary interventions, exercise, specific targeted nutrients, appropriate treatments for infections and toxicity, and multiple lifestyle and supplement strategies to lower my histamine levels. I’ve also made lifestyle changes including, as I said, simplifying (everything), reducing stress, doing more of what I love and building a spiritual practice that reminds me that I control very little in this world, and that I'm part of something larger than myself - here for a purpose...no matter how flexibly inflexible or brilliantly brain foggy I may be on a given day.  Had I known this theory, would I still have changed my life?.. or would I have accepted that much of my destiny was in my genes?

I might actually have changed my life sooner.  I might have welcomed a “good reason” to take better care of myself.  I might have taken the phrase "daily stress” more seriously.

My lifestyle changes and spiritual growth helped me - to put it in more physiologic terms - “shut off my acute stress response,” which was making me sick.  And according to Dr. Meglathery, “If you can figure out how to do that, then the whole cycle of elevated CRH (the stress hormone), inflammatory cascade, Mast Cell Activation Syndrome, and elevated progesterone decreases (not gone but lessens).” 

I wrote this post, because I do believe this understanding can move people more quickly to a diagnosis/es, assist in more effective targeted treatments and help those already in treatment recognize their vulnerabilities and adjust their lifestyle choices accordingly.

There are many roads to healing.  One is the path of intellect and information.  There are endless online groups overflowing with smart people who have a great deal to share.  Such groups have helped me connect some dots. They’ve also kept me focused on illness.  Another path is more mindful, spiritual, or however you want to call feeling at peace in the moment and in your body.  In my own healing, I used and still use both.

I look forward to using the new tools and understanding that Dr. Meglathery’s work brings me for my own health, as well as those who come to my office.  I’m already asking patients, “Are you hyper-mobile, double jointed, extra flexible, have lax joints or is there anyone in your family that you know of who does?”  I’m surprised at how many actually are, or say they aren’t before they unintentionally demonstrate to me that they are.

Dr. Meglathery’s theory has taught me many things, but perhaps none more necessary than the acceptance that my greatest vulnerabilities which have brought me some of my “darkest days” are intimately intertwined with my greatest strengths, which have brought me joy and purpose.  Instead of shying away from some of my abilities, I’m more likely to claim them now.  In all, her discovery has moved me closer to a sense of wholeness - something I wish for anyone reading this.

Thank you to Dr. Sharon Meglathery, her patients and to all of those who are helping to move this information forward.

​For a more detailed explanation of Dr. Meglathery’s work, as well as a list of associated conditions, visit RCCX Theory at: http://www.rccxandillness.com/