Hypermobility, RCCX Theory, Mental Health & Complex Chronic Illness

Meet the cluster of genes that may be at root of many psychiatric conditions and complex chronic illness, MCAS, EDS, POTS, CIRS & CFS.

Hypermobility—having joints that bend further than normal—is a surprisingly common trait in those with brain symptoms. Using RCCX theory, I’ll attempt to explain why this is. RCCX is a gene module (cluster of genes) that appears to be at the foundation of many psychiatric conditions and complex chronic health conditions, such as mast cell activation syndrome (MCAS), chronic fatigue syndrome, chronic inflammatory response syndrome (CIRS), and postural orthostatic tachycardia syndrome (POTS).

This topic is complex but worth the effort.  Though hypermobility can be a red flag for a RCCX vulnerability, this theory can inform us about brain symptoms whether we are hypermobile or not.  

I won’t be sharing my personal health journey, which I did in 2017, in the blog post Hypermobility, RCCX Theory and One Journey From Illness Towards Wholeness. But, if you’ve followed my writing, you’ve likely noticed, I’ve been impacted by many things - undermethylation with a seemingly slow MAOA, copper overload, mast cell activation, candida, mold toxicity, hypermobility with upper cervical instability, and electromagnetic hypersensitivity.  

My health history is actually not so unusual.  There are many people with what we call complex chronic illness.  One of those, to whom I’m especially grateful, is Dr. Sharon Meglathery, M.D.   She is a psychiatrist and internist with a health history very similar to my own.  We first connected in 2017.  Her RCCX theory not only explains chronic complex illness, but also chronic psychiatric conditions in many individuals with or without hypermobility.  This theory is especially good at explaining what happens to a person who was going along fine, until they were hit with severe or multiple stressors or a toxic exposure, which set them into a range of health issues, including brain symptoms like depression, anxiety, panic, mood swings, psychosis, etc.

Because hypermobility appears to be an important red flag for some, I’ll start there and move into RCCX theory…..

1. Connective tissue.  This is what holds us together - not just our joints, but our skin, our blood vessels and our organs including our gastrointestinal tract.  Relatively weak connective tissue can look different in different people and to varying degrees.  Examples include double-jointed knees, elbows, wrists and/or fingers. It can also be dislocations, flat feet, misalignment of the spine, hernias, prolapse at the pelvic floor, osteoporosis, stretchy and/or translucent skin, poor wound healing, stretch marks, varicose veins, low blood pressure (from weak blood vessels), hemorrhoids, aneurysms, a permeable gut blood barrier, problems with motility (movement) of the GI tract, diverticula, mitral valve prolapse…and more.

2. TNXB is a gene that codes for tenascin, a protein involved in collagen architecture.  A mutation here can impact our connective tissue to varying degrees, from none to Ehlers Danlos Syndrome (EDS) - a group of 13 inherited conditions that affect connective tissue. You may always have been more flexible than most without stretching. You may have gravitated towards gymnastics or dance because of this. You may or may not have a few of the connective tissues symptoms mentioned above. You may just have been double-jointed in your fingers. Maybe you have family members who fall on the hypermobility spectrum but don’t yourself.  This family history is relevant here as well. 

3. Can hypermobility alone cause brain symptoms?  As described in a recent post, it can cause upper cervical instability which can impact the vagus nerve, the flow of blood and cerebrospinal fluid in and out of the brain and skull.  A permeable gut blood barrier can cause a leaky gut - meaning food particles or toxins can get through causing immune activation and impacting the brain. Low blood pressure from blood pooling in the legs can result in less blood flow making its way to the brain. Decreased gut motility can lead to constipation and/or SIBO, both of which can impact brain health. But, even with all of this, hypermobility does not appear to be the main driver when it comes to chronic health conditions for many.

4. EDS, MCAS, POTS - a common triad.  It is increasingly recognized that Ehlers Danlos Syndrome (EDS), Mast Cell Activation Syndrome (MCAS), and Postural Orthostatic Tachycardia Syndrome (POTS) frequently occur together.  It is recognized too, that many if not most with this triad have brain-related symptoms and psychiatric diagnoses.  

   1. EDS (as described above) 

   2. MCAS - Mast cells are first responders in the inflammatory response. Those with mast cell activation syndrome have wide-ranging and unpredictable symptoms that occur when mast cells destabilize and release inflammatory mediators. Though not in the brain, they communicate with inflammatory cells in the brain and can trigger brain inflammation.  

   3. POTS - This is when your heart rate increases very quickly after getting up from sitting or lying down.  Symptoms include lightheadedness, fainting, and rapid heartbeat, which are relieved by lying down again.  

      Many people I see don’t have full blown EDS, MCAS or even POTS, but have a degree of all of these or a couple of these along with brain related symptoms.

5. What is uniting EDS, MCAS, POTS and psychiatric conditions and the various spectrums of these? There are different theories.  One is that mast cells are at the root of all of this and are leading the connective tissue symptoms in those with genetic vulnerabilities.  Another theory is that these are all connected by faulty methylation. But the theory that has made the most sense to me over the years (for myself and many people I see) has been RCCX theory.  

6. RCCX.  RCCX itself is not a theory.  It is the name of the identified gene module that the theory is based on.   RCCX is basically a cluster of four genes that are inherited together.  Normally our genes are not inherited together like this.  Not only is this unusual, it’s a big deal because three of these genes are powerhouses when it comes to our health.  Two of the three genes have a high rate of mutations. A mutation in various places on these genes (not yet able to be tested clinically tested for) can impact the functioning of the enzyme that the gene codes for. The main genes and what they code for include include:

(1) TNXB - as mentioned codes for tenascin, a protein involved in collagen architecture and can cause hyper-mobility to varying degrees (from none to Ehlers Danlos).  

(2) CYP21A2 - (which may be one of the most important genes when it comes to psychiatric conditions) codes for an enzyme, 21-hydroxylase - a pivotal enzyme in hormonal pathways. When this enzyme is impaired (due to a mutation), there can be problems keeping up with the demands for cortisol.

(3) C4 - codes for complement C4 - a protein involved in the immune response.  A mutation here could result in autoimmunity and even schizophrenia.

7. RCCX theory:  According to Dr. Meglathery’s theory, this “co-inheritance of a cluster of highly mutable genes may confer vulnerability to familial clusters of overlapping syndromes of chronic illness (hyper-mobility, autoimmune disease, Chronic Fatigue, MCAS, POTS, and psychiatric illness, etc.).” To see the extensive list (too long to include here), visit the RCCX website.  That these genes are inherited as a block, as opposed to being inherited separately, doesn’t mean a mutation in one gene causes a mutation in all.  There does, however, seem to be a high rate of co-inheritance of mutations in two of the genes: - 1) the gene that relates to hypermobility and 2) the gene that relates to an impaired hormonal stress response.  This stress response can result in chronic physical or mental illness, due to the mast cell activation it triggers (which I’ll explain).  While the symptoms and conditions 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.  

8. Wired for danger: The impacts of 21-hydroxylase on the stress response start early.  “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 essentially wired for danger, not unlike the brain of someone with PTSD.  This decreased ability to deal with stress, according to Dr. Meglathery, “raises one’s susceptibility to PTSD/Post Traumatic Stress Disorder  or other forms of disordered emotional processing.” RCCX theory suggests that about 15-20% of us have a mutation on 21-hydroxylase. 

9. Inflammation Connection -  Decreased cortisol levels occur when severe acute or chronic high stress overwhelm the ability of 21-hydroxylase to keep up. Remember it can be relatively weak due to a mutation on CYP21A2. Low cortisol can lead the brain to release more corticotropin-releasing hormone (CRH) telling the adrenal glands “Make more cortisol!!”. The kicker is that mast cells have receptors for CRH, so when stress is high and not enough cortisol is being produced (due to 21-hydroxylase not being able to keep up), inflammation occurs.   This overwhelm of 21-hydroxylase can result in MCAS, POTS, and chronic fatigue syndrome (CSF) also called  myalgic encephalomyelitis (ME).  It can also cause chronic inflammatory and/or biotoxin illness (CIRS).  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.  An RCCX person with mold toxicity, for example, can develop symptoms not just from the mold, but from the consequences of 21-hydroxylase being overwhelmed leading to inflammation (including brain inflammation). Those without RCCX, on the other hand, will mainly have symptoms of mold toxicity. 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. 

10. Hyper-mobility as a red flag. Hypermobility, therefore, can point to a RCCX issue. It could be a big clue as to what’s going on and what tools may be helpful. Recognizing it can be an especially important marker for physicians and other practitioners to consider when meeting anyone seeking help for chronic medical or psychiatric conditions.  For those who are not ill, this symptom or trait may suggest a vulnerability to becoming ill (physically and/or mentally) after acute or chronic stress.  This may impact lifestyle choices.

Had I known about RCCX theory, I might have made changes in my own 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.

Getting sick forced me to simplify every aspect of my life.  I'd lost energy for and could no longer tolerate television, stuff, ego driven aspirations, many people…. I let go of relationships and activities that were no longer meaningful for me.  As I healed, I started adding in what I loved, I learned to pace myself, I built spiritual practices that reminded me that I control very little in this world, that I'm part of something larger than myself - here for a purpose, and that there is meaning even in our suffering.”  

Those lifestyle changes and my spiritual growth helped me, “shut off my acute stress response,” which was making me sick (along with mold toxicity).  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).” Though I’m of the belief that there are various paths to lowering the stress response, Dr. Meglathery finds EMDR to be especially important. 

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/

Thank you for sticking with me on this one.  As always, I welcome your thoughts and questions.

Until next time,

Courtney

P.S. Paid subscribers - watch out for a post midweek, where I’ll discuss other traits often associated with RCCX, including natural strengths and physical characteristics such as finger length ratio. I’ll also comment on how RCCX very well may relate to pyrrole disorder.

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Medical Disclaimer: This newsletter is for educational purposes and not intended or implied to be a substitute for professional medical advice, diagnosis or treatment for either yourself or others, including but not limited to patients that you are treating (if you are a practitioner). Consult your own physician for any medical and psychiatric issues that you may be having.

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