MEGLATHERY MD: RCCX MAY EXPLAIN OVERLAPPING SYNDROMES ASSOCIATED WITH CHRONIC ILLNESS (EDS-HT, CFS, FM, LYME, MCAS, POTS, PAIN, PSYCHIATRIC SPECTRUM, IMMUNOLOGICAL, ENDOCRINE ISSUES). NEUROPSYCHIATRIC MARKER, CAPS, PREDICTS RISK.
Welcome: Hello All, I am Sharon Meglathery MD (aka Dr. Sharon, stripey14), a physician (see About Section) who developed mast cell activation (MCAS), postural orthostatic tachycardia syndrome (POTS), raised intracranial pressure, chronic fatigue syndrome (CFS) and a host of other potentially disabling syndromes in the setting of Ehlers-Danlos Syndrome (EDS-HT) in 2009. I was shocked to learn that somehow medical education has completely missed an epidemic affecting so many gifted young people (mostly women), leaving the patients to fend for themselves. I have spent 7 years obsessed with a long list of seemingly connected, overlapping syndromes, gathering patient observations in my clinic and in the forums, scouring the scientific literature, dealing with my own illness and often having to experiment on myself. Early on, my broad medical background revealed that several commonly held assumptions about these conditions must be false. By letting those assumptions go, I was able to find a neuropsychiatric marker, dubbed CAPS, which predicts a higher risk of chronic illness regardless of hypermobility status which has stood the test of several years. From there, a lucky break revealed a set of candidate genes which pulled all of my observations together. The knowledge of these genes changed the course of my illness by presenting novel treatment options, and I expect will pave the way for new pharmaceuticals which will help us.
I believe that the RCCX Theory solves some of medicine and psychiatry's greatest mysteries. The RCCX Theory explains the co-inheritance of a wide range of overlapping chronic medical conditions in individuals and families (EDS/hypermobility, autoimmune diseases, chronic fatiguing illness, psychiatric conditions, autism, etc.). It explains the underlying pathophysiology of chronic fatiguing illnesses with so many overlapping features (EDS-HT, CFS, Chronic Lyme Disease, Fibromyalgia, toxic mold, Epstein Barr Infection, MCAS, POTS, etc.). And finally, it reveals the gene which I believe confers a predisposition toward brilliance, gender fluidity, autistic features, and stress vulnerability, as well as the entire spectrum of psychiatric conditions (other than schizophrenia which can be co-inherited). This website contains everything you need to understand the subtleties of this theory.
The first part of the RCCX Theory was born in July 2015. I tried desperately to share it, but I was not successful using traditional methods. I released the first version of this website in February 2016. The website was designed so that the theory would be accessible to everyone, patients and researchers alike. I also included downloadable versions of a Summary for Scientists, Journal Article (now outdated) with references and my pathophysiology diagrams for easy transport. I hoped it would go viral and the information would get to scientists who may be interested in pursuing this.
Developments Since Initial Release of the Website in February 2016:
In the first couple days of release, I was approached by Karen Herbst MD PhD, Endocrinology who was interested in helping me prove this hypothesis. She and I started a non profit corporation to fund studies exploring the role of the RCCX Module in Chronic Illness. Unfortunately, we have realized that studying the genetic portion of this could be too complex for even a university genetics lab, given the complexity of the RCCX module. We also came to see that endocrine testing is also fraught with difficulty, given the way that the clinical response to stress is very dependent on the overall stress load and length of time a person is stressed (CFS studies show normal stress response followed by high fatiguability on rechallenge) and the fact that no testing has been able to reliably distinguish CYP21A2 carriers from normals. We decided to proceed with a questionnaire demonstrating that the RCCX comorbidities run in individuals and families as a way to get researchers interested. I spent 2 years gathering info from people fitting the RCCX phenotype to make the questionnaire as comprehensive as possible. (I run a discussion group on FB called RCCX and Chronic Illness Discussion). I completed it and gave it to Karen and her team in January of 2018 and had to cut back my involvement due to my health issues. There has not been much progress since then, but I do have permission to share the questionnaire with other interested researchers. All funds collected through the RCCX Project will go to any viable research effort looking at the role of the RCCX module in chronic illness and Ron Davis PhD as a default. I am no longer fund-raising.
In June 2016, a pilot study conducted by Robert Naviaux MD PhD and Ron Davis PhD revealed that mitochondrial shutdown triggered by stress is the likely final pathway in CFS/ME. With this news, I updated the website in July of 2016. I added RCCX Theory Part II to demonstrate how the RCCX Theory provides several highly likely paths to mitochondrial shutdown, including a psychiatric path which I explained fully in the new CAPS section. I edited the rest of the website to show that "CAPS" now stands for CYP21A2 Mutation Associated Neuropsychiatric Spectrum which is a more accurate name than the previous one. The website also now reflects that there are probably many afflicted with chronic illness who are actually homozygotes for mild CYP21A2 mutations, in addition to the heterozygotes I had discussed previously. I believe this is true because people with CAPS are attracted preferentially to other people with CAPS.
By March 2017, there were many developments, all heading in the direction of RCCX Theory, so I decided to add a quick New Developments Section until I could sit down and really write the next chapter. I am increasingly confident that Ron Davis PhD et al. will arrive at the RCCX Theory probably sooner than later as he has said that there seems to be a genetic predisposition to "pushing through" which leads to chronic illness by repeatedly telling the body to shut down the Kreb's cycle. I strongly believe that carriers of CYP21A2 mutations with CAPS are predisposed to pushing through stress because of higher than normal arousal when stressed and then fighting against low basal cortisol to continue to be productive. We also know that many of those with EDS (those with CAPS, I believe) have high adrenaline/sympathetic nervous system tone which can also allow this to happen. Further, it is becoming clear that some folks respond amazingly well (in terms of energy and cortisol production) to bioactive chelated copper supplementation (this is special copper not the usual supplement), myself included. I think those with mutations for defective (as opposed to low amounts) of 21 hydroxylase may be at risk for bioactive copper deficiency which adds a layer of heme-containing enzyme failure and inappropriate heme deposition in places like the brain (heme has recently been found to be inappropriately deposited in brains of people with MS, which I believe is very much an RCCX comorbidity) and maybe in the urine (?pyroluria). More about that can be found in the New Developments section.
How you Can Help:
I believe that the RCCX Theory solves some of medicine and psychiatry's greatest mysteries. The RCCX Theory explains the co-inheritance of a wide range of overlapping chronic medical conditions in individuals and families (EDS/hypermobility, autoimmune diseases, chronic fatiguing illness, psychiatric conditions, autism, etc.). It explains the underlying pathophysiology of chronic fatiguing illnesses with so many overlapping features (EDS-HT, CFS, Chronic Lyme Disease, Fibromyalgia, toxic mold, Epstein Barr Infection, MCAS, POTS, etc.). And finally, it reveals the gene which I believe confers a predisposition toward brilliance, gender fluidity, autistic features, and stress vulnerability, as well as the entire spectrum of psychiatric conditions (other than schizophrenia which can be co-inherited). This website contains everything you need to understand the subtleties of this theory.
The first part of the RCCX Theory was born in July 2015. I tried desperately to share it, but I was not successful using traditional methods. I released the first version of this website in February 2016. The website was designed so that the theory would be accessible to everyone, patients and researchers alike. I also included downloadable versions of a Summary for Scientists, Journal Article (now outdated) with references and my pathophysiology diagrams for easy transport. I hoped it would go viral and the information would get to scientists who may be interested in pursuing this.
Developments Since Initial Release of the Website in February 2016:
In the first couple days of release, I was approached by Karen Herbst MD PhD, Endocrinology who was interested in helping me prove this hypothesis. She and I started a non profit corporation to fund studies exploring the role of the RCCX Module in Chronic Illness. Unfortunately, we have realized that studying the genetic portion of this could be too complex for even a university genetics lab, given the complexity of the RCCX module. We also came to see that endocrine testing is also fraught with difficulty, given the way that the clinical response to stress is very dependent on the overall stress load and length of time a person is stressed (CFS studies show normal stress response followed by high fatiguability on rechallenge) and the fact that no testing has been able to reliably distinguish CYP21A2 carriers from normals. We decided to proceed with a questionnaire demonstrating that the RCCX comorbidities run in individuals and families as a way to get researchers interested. I spent 2 years gathering info from people fitting the RCCX phenotype to make the questionnaire as comprehensive as possible. (I run a discussion group on FB called RCCX and Chronic Illness Discussion). I completed it and gave it to Karen and her team in January of 2018 and had to cut back my involvement due to my health issues. There has not been much progress since then, but I do have permission to share the questionnaire with other interested researchers. All funds collected through the RCCX Project will go to any viable research effort looking at the role of the RCCX module in chronic illness and Ron Davis PhD as a default. I am no longer fund-raising.
In June 2016, a pilot study conducted by Robert Naviaux MD PhD and Ron Davis PhD revealed that mitochondrial shutdown triggered by stress is the likely final pathway in CFS/ME. With this news, I updated the website in July of 2016. I added RCCX Theory Part II to demonstrate how the RCCX Theory provides several highly likely paths to mitochondrial shutdown, including a psychiatric path which I explained fully in the new CAPS section. I edited the rest of the website to show that "CAPS" now stands for CYP21A2 Mutation Associated Neuropsychiatric Spectrum which is a more accurate name than the previous one. The website also now reflects that there are probably many afflicted with chronic illness who are actually homozygotes for mild CYP21A2 mutations, in addition to the heterozygotes I had discussed previously. I believe this is true because people with CAPS are attracted preferentially to other people with CAPS.
By March 2017, there were many developments, all heading in the direction of RCCX Theory, so I decided to add a quick New Developments Section until I could sit down and really write the next chapter. I am increasingly confident that Ron Davis PhD et al. will arrive at the RCCX Theory probably sooner than later as he has said that there seems to be a genetic predisposition to "pushing through" which leads to chronic illness by repeatedly telling the body to shut down the Kreb's cycle. I strongly believe that carriers of CYP21A2 mutations with CAPS are predisposed to pushing through stress because of higher than normal arousal when stressed and then fighting against low basal cortisol to continue to be productive. We also know that many of those with EDS (those with CAPS, I believe) have high adrenaline/sympathetic nervous system tone which can also allow this to happen. Further, it is becoming clear that some folks respond amazingly well (in terms of energy and cortisol production) to bioactive chelated copper supplementation (this is special copper not the usual supplement), myself included. I think those with mutations for defective (as opposed to low amounts) of 21 hydroxylase may be at risk for bioactive copper deficiency which adds a layer of heme-containing enzyme failure and inappropriate heme deposition in places like the brain (heme has recently been found to be inappropriately deposited in brains of people with MS, which I believe is very much an RCCX comorbidity) and maybe in the urine (?pyroluria). More about that can be found in the New Developments section.
How you Can Help:
- Please continue to distribute this theory widely to other patients so that they can know that help may soon be on the way.
- Talk about it.
- Write about it on your websites.
- Please like the Facebook page: RCCX and Chronic Illness for updates.
- My email address is [email protected] for questions and suggestions.
- Join the FB discussion group: RCCX and Chronic Illness Discussion to expand and refine the theory.
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Disclaimer: The purpose of this website is NOT to recruit patients, give treatment recommendations, sell supplements, get attention, be controversial or become famous. I live a quiet, reclusive life with a small, local and full medical practice. This illness and this discovery has made my life very complicated.
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To Whom Does This Theory Pertain?
I assume that most of my audience consists of chronically ill patients who suffer from one and probably many of the chronic syndromes/symptoms/diseases which I will list shortly. Please understand that I am NOT saying that everyone with these diagnoses fits in this group; rather I am saying that in many families, a cluster of these diagnoses will be found and I believe that those families are likely to contain the gene mutations I discuss. For example-you may see a family with a member, often female, diagnosed with or suspected to have Ehlers-Danlos Syndrome, Hypermobility Type (EDS-HT), postural orthostatic tachycardia syndrome (POTS) and mast cell activation syndrome (MCAS). Then in the extended family, you may find autoimmune diseases, i.e. multiple sclerosis, cutting and eating disorders, "possible bipolar disorder," gender fluidity, a highly successful and innovative genius, someone with chronic fatigue syndrome (CFS) or fibromyalgia (FM), someone with severe post-traumatic stress disorder (PTSD) and someone else with bouts of psychosis. The children who are more scrutinized in this day and age, may be diagnosed with attention deficit disorder (ADD), sensory processing issues plus or minus Asperger's Disorder (I know, I know, not in the DSMV:>)). And the kicker, these issues may be found on both sides of the family because I believe that we are attracted to each-other. There is a characteristic psychological profile (CAPS) which goes with this: sensitive, emotional, often gifted and we tend to surround ourselves with others who share these traits.) The degree of hypermobility ranges from none to severe in this family and correlates with the degree of musculoskeletal involvement (joint pain/dislocations/surgeries required to stabilize joints) and orthostasis/"dysautonomia," but not with the other "sick" symptoms which tend to develop later in life only in some, mostly women but not always. Many will react strongly to stress. If this sounds like your family (albeit a dramatic version), I am writing this for you.
Of note: These conditions can occur due to other genes, thus occurring without these clusters. Many people with MCAS and POTS, together or alone have these for a different reason. What I am writing is NOT relevant to them. (However, if you have bendy joints and MCAS and POTS, I am talking to you!)
Over time, it has become clear to anyone who frequents the chronic illness forums, sees patients with an open mind or keeps up with the literature in this field that there seems to be a frequently disabling epidemic involving a large number of syndromes/symptoms/diseases with overlapping symptoms affecting mainly young, vibrant, talented people (predominantly women) and if you look, many, but not all, have joint hypermobility (double jointedness, ligament laxity). These are (to name a few and I'm probably leaving some out inadvertently):
I will refer to all of these under the rubric of "Chronic Illness" going forward.
For those of you with EDS, it is important that I clarify a few points. My theory pertains to those who have not been found to have a specific disease-causing collagen mutation, i.e. those who fall into the hypermobile and classical types. I will show you that I believe that we have life-long issues due to poor collagen and inflammation from TGF beta resulting from a TNXB mutation PLUS a propensity for other stress-triggered systemic issues similar to those with other chronic illnesses from an adjacent gene, CYP21A2. I will show you why the current assumption that TNXB mutations are a rare cause of EDS-HT is incorrect, and I will show you why, today, it is impossible to test for even a fraction of the TNXB mutations associated with clinical illness. I know that this goes against the EDS teaching/knowledge base, but keep reading and you will see why I have come to these conclusions. (Background Section followed by RCCX Theory Part I )
I assume that most of my audience consists of chronically ill patients who suffer from one and probably many of the chronic syndromes/symptoms/diseases which I will list shortly. Please understand that I am NOT saying that everyone with these diagnoses fits in this group; rather I am saying that in many families, a cluster of these diagnoses will be found and I believe that those families are likely to contain the gene mutations I discuss. For example-you may see a family with a member, often female, diagnosed with or suspected to have Ehlers-Danlos Syndrome, Hypermobility Type (EDS-HT), postural orthostatic tachycardia syndrome (POTS) and mast cell activation syndrome (MCAS). Then in the extended family, you may find autoimmune diseases, i.e. multiple sclerosis, cutting and eating disorders, "possible bipolar disorder," gender fluidity, a highly successful and innovative genius, someone with chronic fatigue syndrome (CFS) or fibromyalgia (FM), someone with severe post-traumatic stress disorder (PTSD) and someone else with bouts of psychosis. The children who are more scrutinized in this day and age, may be diagnosed with attention deficit disorder (ADD), sensory processing issues plus or minus Asperger's Disorder (I know, I know, not in the DSMV:>)). And the kicker, these issues may be found on both sides of the family because I believe that we are attracted to each-other. There is a characteristic psychological profile (CAPS) which goes with this: sensitive, emotional, often gifted and we tend to surround ourselves with others who share these traits.) The degree of hypermobility ranges from none to severe in this family and correlates with the degree of musculoskeletal involvement (joint pain/dislocations/surgeries required to stabilize joints) and orthostasis/"dysautonomia," but not with the other "sick" symptoms which tend to develop later in life only in some, mostly women but not always. Many will react strongly to stress. If this sounds like your family (albeit a dramatic version), I am writing this for you.
Of note: These conditions can occur due to other genes, thus occurring without these clusters. Many people with MCAS and POTS, together or alone have these for a different reason. What I am writing is NOT relevant to them. (However, if you have bendy joints and MCAS and POTS, I am talking to you!)
Over time, it has become clear to anyone who frequents the chronic illness forums, sees patients with an open mind or keeps up with the literature in this field that there seems to be a frequently disabling epidemic involving a large number of syndromes/symptoms/diseases with overlapping symptoms affecting mainly young, vibrant, talented people (predominantly women) and if you look, many, but not all, have joint hypermobility (double jointedness, ligament laxity). These are (to name a few and I'm probably leaving some out inadvertently):
- Ehlers-Danlos Syndrome, Hypermobility Type (EDS-HT)
- Chronic fatigue Syndrome (CFS)/Myalgic Encephalomyelitis (ME)
- Fibromyalgia (FM)
- Chronic Lyme Disease, Gulf War Syndrome, Toxic Mold/Biologic Illness
- Mast Cell Activation Syndrome (MCAS): histamine intolerance, migraines, diarrhea, sinus pain, burning eyes, syncope, distractibility, brain fog, irritability, interstitial cystitis, hyper-adrenergic POTS, etc., depending on location of the mast cells
- Postural Orthostatic Tachycardia (POTS), Dysautonomia, Orthostatic Intolerance, Low Blood volume
- Pain Syndromes: Neuropathic Pain Syndromes/Chronic Regional Pain Syndrome/Myofascial Pain Disorder/Frequent Dislocations/Dysmenorrhea/Chronic Headache/Migraines/Interstitial Cystitis/Vulvodynia/Temporomandibular Joint Disorder (TMJ)
- GI Syndromes: Irritable Bowel Syndrome/Cyclical Vomiting/Gastroparesis/Food Intolerance/Gut dysbiosis/Candida overgrowth/Leaky Gut Syndromes/Malabsorption Syndromes
- Raised Intracranial Pressure Conditions: Pseudotumor Cerebri/Benign Intracranial Hypertension/Posterior Reversible Encephalopathy/Acquired Chiari Malformation
- Neurological Issues: Neuropathies/Pain Syndromes/Uncoordinated Swallow/Vertigo/Central Apnea/Sleep Paralysis/Dysautonomia/Seizure-Like Episodes/Dystonia/Narcolepsy/White Matter Lesions/Small Fiber Polyneuropathy (Erythromelalgia)/Restless Leg Syndrome/Brain Anatomic Abnormalities (big Amygdalae-fear and emotional center; small anterior cingulate; chiari malformation, hydrocephalus)
- Mitochondrial Disorders
- Immune Dysregulation: Combined Variable Immunodeficiency (CVID)/IgA deficiency/fungal infections/recurrent HSV infections/no colds for years, severe bacterial infections, inability to clear strep/Epstein Barr/mycoplasma/chlamydia/candida, dysbiosis, small intestinal bacterial overgrowth, multiple sclerosis (MS), autoimmune disorders-classic and non classic, i.e. mixed connective tissue disorders/eosinophilic disorders, high TGF beta/inflammatory conditions (endometriosis, etc.), Chronic Inflammatory Response Syndrome (CIRS)
- Psychiatric Issues: Psychiatric Conditions due to Dysautonomia (Panic/Anxiety)/ADD/Hyperfocus/Autistic Wiring/Sensory Processing Disorders/Psychosis/Schizophrenia/Chronic Illness: Stress and Loss/PTSD/Mood Disorders (Bipolar/Unipolar)/Chronic Insomnia/Generalized Anxiety Disorder/Obsessive Compulsive Disorder/Phobias/Obsessive Compulsive Personality Disorder/Paranoid Disorders/Emotional Dysregulation/Compulsive Behaviors
- Hormonal Disorders: Sex Hormone Disorders-Cystic Ovaries, Acne, Water +/- Fat Associated Weight Gain, Breast and Tissue Swelling, Fertility issues, Hot Flashes/Night Sweats; Adrenal Gland Issues: Adrenal Fatigue, Addison's, High/Low Cortisol, Low Aldosterone; Pituitary Hormone Abnormalities-ACTH, TRH-Mediated Thyroid Disorders; Autoimmune Hormonal Issues (i.e. Hashimotos's Thyroiditis), etc...
- GU/Renal Issues: Fibromuscular Dysplasia, Diabetes Insipidus, Interstitial Cystitis, Vesicoureteral Reflux
- Misc.: Extreme Temperature Dysregulation (Dysautonomia or not), Multiple Chemical Sensitivity, High Adrenaline/Noradrenaline (also called norepinephrine) States, Erythromyalalgia, Raynaud's, Livedo Reticularis, Evidence of Poor connective tissue integrity (dislocations, bruising, bleeding, petechaie, calcific aortic valves, Mitral Valve Prolapse, etc), Dry eyes, Tinnitis, Subcutaneous Adipose Disorders (Lipidema, Dercum's Disease), Left Handedness, Gender Fluidity (LGTB, lack of traditional gender roles),
- Perhaps: Medullary Sponge Kidney, Pyroluria, disorders of copper and zinc regulation, Early Onset Parkinson's Disease
I will refer to all of these under the rubric of "Chronic Illness" going forward.
For those of you with EDS, it is important that I clarify a few points. My theory pertains to those who have not been found to have a specific disease-causing collagen mutation, i.e. those who fall into the hypermobile and classical types. I will show you that I believe that we have life-long issues due to poor collagen and inflammation from TGF beta resulting from a TNXB mutation PLUS a propensity for other stress-triggered systemic issues similar to those with other chronic illnesses from an adjacent gene, CYP21A2. I will show you why the current assumption that TNXB mutations are a rare cause of EDS-HT is incorrect, and I will show you why, today, it is impossible to test for even a fraction of the TNXB mutations associated with clinical illness. I know that this goes against the EDS teaching/knowledge base, but keep reading and you will see why I have come to these conclusions. (Background Section followed by RCCX Theory Part I )
MEGLATHERY MD: RCCX THEORY
I believe that many cases of these overlapping medical issues/diseases/syndromes/symptoms result from just a few mutated genes which tend to travel together in contiguous (side by side) mutations in the only part of the human genome where that can happen, the RCCX module. In other words, these mutations mix and match to produce different patterns of these conditions within families, dependent on the severity of the mutation, the amount of stress involved (e.g. the CYP21A2 mutation) and the presence of other mutations which can enhance or decrease the overall severity of illness. This is why these conditions occur in a high rate in hypermobile folks but hypermobility is not necessary to go down this path.
The genes of interest include CYP21A2 which codes for a crucial enzyme involved in the acute stress response (21 hydroxylase), TNXB which codes for tenascin, an important matrix protein implicated in EDS-HT and C4, a gene involved in the complement system and implicated in schizophrenia, CVID, MS, lupus and other autoimmune diseases.
I believe that these genes, particularly C4 and CYP21A2 sit in the most highly mutagenic part of the genome because mutations of these genes provide novel ways of responding to ever-changing environments in terms of response to pathogens/brain wiring for C4 and stress response/brain wiring for CYP21A2.
I posit that only one copy of a CYP21A2 mutation is necessary to create a stress vulnerability in its recipient which can have catastrophic consequences in settings of severe acute or chronic/prolonged stress, resulting in medical and/or psychiatric illness. I believe that this is an evolutionarily programmed response to very high stress, resulting in decreased procreation and ultimately, the removal of the mutation from the gene pool.
There are 2 reasons for this stress vulnerability: 1. CYP21A2-induced spiking cortisol in utero and infancy leading to a brain wired for danger which then develops full PTSD-like wiring as stress continues and 2. With prolonged stress, the body can no longer make adequate 21hydroxylase which then initiates inflammatory cascades/mast cell activation with or without the addition of the C4 mutation which adds autoimmune disease and increases the severity of the inflammatory response (pathophysiology diagram).
I posit that a child carrying a CYP21A2 mutation has the same brain as a child raised in adverse circumstances, with enlarged limbic structures (amygdala), wired-in dysautonomia and primed connections in the limbic and neuroendocrine systems. This is a brain wired for danger, (CAPS, CYP21A2 Associated NeuroPsychiatric Spectrum). With increased threat detection and enhanced stress response comes some gifts, if present in moderation: enhanced empathy (ability to read emotions in others), sensory sensitivity, superior pattern recognition/information processing, times of intense hyperfocus/obsession/special interests and unusual abilities (often in music, arts or abstract thinking) . With any stress (even minimal trauma), the threat response circuits are reinforced and epigenetic changes can further strengthen these connections, creating PTSD-like wiring and reactions. These stress-induced/primed circuits in the brainstem and limbic system can be associated with the emergence of bursts of emotional dysregulation, dysautonomia, motor and sensory syndromes (hallucinations, dystonia, catatonia, cataplexy, non-dermatomal sensory symptoms, non-epileptic seizures, etc.) and inappropriate states of consciousness (fight/flight, freeze, shutdown).
I have found that classic psychiatric illnesses almost always present with CAPS, with or without the PTSD wiring. In fact, I believe that CYP21A2 mutations are the genetic basis for the development of four of the five major psychiatric illnesses (anxiety disorders, mood disorders, ADD, autism), with C4 (next door) +/! coinherited CYP21A2 being responsible for the 5th, schizophrenia (shown in January 2016). The fact that in April 2015 it was shown that these major psychiatric illnesses are likely part of a spectrum with similar genetic underpinnings fits very nicely with the RCCX Theory.
I have found that CAPS is invariably present in hypermobile psychiatric patients who develop chronic illness and is present in the vast majority of people who develop chronic illness. I believe that it is a reliable marker for vulnerability of developing chronic illness.
I believe that 21 hydroxylase overwhelm, this PTSD wiring, downstream effects from TNXB mutations (via high TGF beta) and C4 mutations (autoimmune disease) can trigger and maintain an adaptive shutdown response of the mitochondria which occurs under stress. This mitochondrial shutdown was recently demonstrated in a pilot study of severely ill CFS/ME patients (Robert Naviaux MD PhD, June 2016 verbal results, published results 8/30/16).
CYP21A2 mutations are in upwards of 20% of the population and I believe that they may be the most important risk factor for PTSD and mitochondrial shutdown. TNXB and C4 mutations are also extremely common.
Unfortunately, while some of the mutations affecting these genes have been characterized (some of the TNXB mutations, some of the CYP21A2 mutations), the evidence suggests that there is CURRENTLY NO WAY TO TEST FOR MOST OF THESE MUTATIONS EVEN WITH 23andme. livewello and promethease and other services. We NEED scientists to do more DNA sequencing of these genes so that we can know which genetic variances cause problems. Unfortunately, IT IS UP TO US TO CONVINCE THEM TO GET STARTED. Knowledge of a CYP21A2 mutation provides immediate prevention and treatment considerations which, in fact, have turned my illness around to a large degree.
- Co-inherited gene mutations of the RCCX module may explain presence of clusters of genetic illness in families and individuals involving hypermobility/fibrosis (TNXB gene), chronic medical illness (CYP21A2 gene, i.e. EDS-HT, CFS/ME, FM, POTS, MCAS, etc.), psychiatric illness (CYP21A2 gene) and autoimmune diseases (C4 gene).
- CYP21A2 gene mutations could confer a stress vulnerability for the development of chronic medical illness (EDS-HT, CFS/ME, FM, POTS, MCAS, etc.) via "21hydroxylase overwhelm" and via PTSD-wiring from CAPS (CYP21A2 Mutation Associated Neuropsychiatric Spectrum) plus negative events.
- CYP21A2 gene mutations create a hormone milieu which could affect the developing brain, making it a "brain wired for danger" by age 5, also known as CAPS (CYP21A2 Mutation Associated Psychiatric Spectrum).
- CAPS likely predisposes to 4/5 of the major psychiatric illnesses (anxiety disorders, mood disorders, attentional disorders, autism spectrum). Both "21hydroxylase overwhelm" and PTSD wiring associated with CAPS could cause stress-induced mitochondrial shutdown (Naviaux MD PhD).
I believe that many cases of these overlapping medical issues/diseases/syndromes/symptoms result from just a few mutated genes which tend to travel together in contiguous (side by side) mutations in the only part of the human genome where that can happen, the RCCX module. In other words, these mutations mix and match to produce different patterns of these conditions within families, dependent on the severity of the mutation, the amount of stress involved (e.g. the CYP21A2 mutation) and the presence of other mutations which can enhance or decrease the overall severity of illness. This is why these conditions occur in a high rate in hypermobile folks but hypermobility is not necessary to go down this path.
The genes of interest include CYP21A2 which codes for a crucial enzyme involved in the acute stress response (21 hydroxylase), TNXB which codes for tenascin, an important matrix protein implicated in EDS-HT and C4, a gene involved in the complement system and implicated in schizophrenia, CVID, MS, lupus and other autoimmune diseases.
I believe that these genes, particularly C4 and CYP21A2 sit in the most highly mutagenic part of the genome because mutations of these genes provide novel ways of responding to ever-changing environments in terms of response to pathogens/brain wiring for C4 and stress response/brain wiring for CYP21A2.
I posit that only one copy of a CYP21A2 mutation is necessary to create a stress vulnerability in its recipient which can have catastrophic consequences in settings of severe acute or chronic/prolonged stress, resulting in medical and/or psychiatric illness. I believe that this is an evolutionarily programmed response to very high stress, resulting in decreased procreation and ultimately, the removal of the mutation from the gene pool.
There are 2 reasons for this stress vulnerability: 1. CYP21A2-induced spiking cortisol in utero and infancy leading to a brain wired for danger which then develops full PTSD-like wiring as stress continues and 2. With prolonged stress, the body can no longer make adequate 21hydroxylase which then initiates inflammatory cascades/mast cell activation with or without the addition of the C4 mutation which adds autoimmune disease and increases the severity of the inflammatory response (pathophysiology diagram).
I posit that a child carrying a CYP21A2 mutation has the same brain as a child raised in adverse circumstances, with enlarged limbic structures (amygdala), wired-in dysautonomia and primed connections in the limbic and neuroendocrine systems. This is a brain wired for danger, (CAPS, CYP21A2 Associated NeuroPsychiatric Spectrum). With increased threat detection and enhanced stress response comes some gifts, if present in moderation: enhanced empathy (ability to read emotions in others), sensory sensitivity, superior pattern recognition/information processing, times of intense hyperfocus/obsession/special interests and unusual abilities (often in music, arts or abstract thinking) . With any stress (even minimal trauma), the threat response circuits are reinforced and epigenetic changes can further strengthen these connections, creating PTSD-like wiring and reactions. These stress-induced/primed circuits in the brainstem and limbic system can be associated with the emergence of bursts of emotional dysregulation, dysautonomia, motor and sensory syndromes (hallucinations, dystonia, catatonia, cataplexy, non-dermatomal sensory symptoms, non-epileptic seizures, etc.) and inappropriate states of consciousness (fight/flight, freeze, shutdown).
I have found that classic psychiatric illnesses almost always present with CAPS, with or without the PTSD wiring. In fact, I believe that CYP21A2 mutations are the genetic basis for the development of four of the five major psychiatric illnesses (anxiety disorders, mood disorders, ADD, autism), with C4 (next door) +/! coinherited CYP21A2 being responsible for the 5th, schizophrenia (shown in January 2016). The fact that in April 2015 it was shown that these major psychiatric illnesses are likely part of a spectrum with similar genetic underpinnings fits very nicely with the RCCX Theory.
I have found that CAPS is invariably present in hypermobile psychiatric patients who develop chronic illness and is present in the vast majority of people who develop chronic illness. I believe that it is a reliable marker for vulnerability of developing chronic illness.
I believe that 21 hydroxylase overwhelm, this PTSD wiring, downstream effects from TNXB mutations (via high TGF beta) and C4 mutations (autoimmune disease) can trigger and maintain an adaptive shutdown response of the mitochondria which occurs under stress. This mitochondrial shutdown was recently demonstrated in a pilot study of severely ill CFS/ME patients (Robert Naviaux MD PhD, June 2016 verbal results, published results 8/30/16).
CYP21A2 mutations are in upwards of 20% of the population and I believe that they may be the most important risk factor for PTSD and mitochondrial shutdown. TNXB and C4 mutations are also extremely common.
Unfortunately, while some of the mutations affecting these genes have been characterized (some of the TNXB mutations, some of the CYP21A2 mutations), the evidence suggests that there is CURRENTLY NO WAY TO TEST FOR MOST OF THESE MUTATIONS EVEN WITH 23andme. livewello and promethease and other services. We NEED scientists to do more DNA sequencing of these genes so that we can know which genetic variances cause problems. Unfortunately, IT IS UP TO US TO CONVINCE THEM TO GET STARTED. Knowledge of a CYP21A2 mutation provides immediate prevention and treatment considerations which, in fact, have turned my illness around to a large degree.
Website Organization
In the Background section, I explain what is observed and currently known about the relationship between these conditions and who gets them and then I move on to my observations and reasoning, exposing more than a few false assumptions/myths which have blocked progress along the way. This section is a pared down version of my path and is written in very basic terms for the non-scientist (containing no references and technical terms). RCCX Theory Part I, illustrates how all of the chronic illness associated diseases and medical syndromes could arise from this gene complex and how they may all interrelate. RCCX Theory Part II discusses how the RCCX Theory links up to stress-induced mitochondrial shutdown, demonstrated in the pilot study on severely ill patients with CFS/ME,conducted by Robert Naviaux MD PhD and Ron Davis PhD. The CAPS section discusses what CAPS is, how it presents, how it develops, how it predisposes to the development of PTSD-like wiring with dissociative brainstem and limbic system responses and how it can lead to mitochondrial shutdown as well. Further, the CAPS section elaborates on how CAPS predisposes for the development of all of the major psychiatric illnesses as well as genius and gender fluidity.
I am hoping that these 3 sections will be enough to demonstrate that this theory explains familial clusters of illnesses/ways of being, most of the exasperating symptoms of chronic illness, the pros and cons of being being "wired for danger" and the importance of stress reduction (physical, illness-related and emotional) in preventing and healing from chronic illness.
I have included a Summary For Scientists, a pared down version, which may be a bit difficult to follow because the RCCX Theory has so much to it, but I did my best.
The Downloads Section includes downloadable versions of Summary For Scientists and the Pathophysiology Diagrams for easy transport to researchers/expert clinicians who may be interested.
The New Developments Section was added March 2017 in response to more revelations from the Open Medicine Foundation/Ron Davis PhD, recently published information and observations from the Facebook RCCX and Chronic Illness Discussion Group which add to and align with the RCCX Theory.
PLEASE, IF YOU THINK I MAY BE RIGHT, SHARE THIS WIDELY.
I will announce additions to this website via the facebook page, RCCX and Chronic Illness (please like), the FB group, RCCX and Chronic Illness Discussion and twitter, @RCCXTheory_MD.
I am hoping that these 3 sections will be enough to demonstrate that this theory explains familial clusters of illnesses/ways of being, most of the exasperating symptoms of chronic illness, the pros and cons of being being "wired for danger" and the importance of stress reduction (physical, illness-related and emotional) in preventing and healing from chronic illness.
I have included a Summary For Scientists, a pared down version, which may be a bit difficult to follow because the RCCX Theory has so much to it, but I did my best.
The Downloads Section includes downloadable versions of Summary For Scientists and the Pathophysiology Diagrams for easy transport to researchers/expert clinicians who may be interested.
The New Developments Section was added March 2017 in response to more revelations from the Open Medicine Foundation/Ron Davis PhD, recently published information and observations from the Facebook RCCX and Chronic Illness Discussion Group which add to and align with the RCCX Theory.
PLEASE, IF YOU THINK I MAY BE RIGHT, SHARE THIS WIDELY.
I will announce additions to this website via the facebook page, RCCX and Chronic Illness (please like), the FB group, RCCX and Chronic Illness Discussion and twitter, @RCCXTheory_MD.
CONTACT INFORMATION:
Sharon Meglathery MD
Email: [email protected]
FACEBOOK: RCCX and Chronic Illness Discussion
Offices: Sharon Meglathery MD, 1661 North Swan Road, Suite 102, Tucson, AZ 85712
Sharon Meglathery MD
Email: [email protected]
FACEBOOK: RCCX and Chronic Illness Discussion
Offices: Sharon Meglathery MD, 1661 North Swan Road, Suite 102, Tucson, AZ 85712