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Is ME due to Ehlers-Danlos Syndrome "stretchy veins"

Discussion in 'Connective Tissue Disorders/Ehlers-Danlos Syndrome' started by Allyson, Nov 12, 2012.

  1. Allyson

    Allyson *****

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    i dd not want to mention names Sushi but that doc has also refered at least one ME/cfs patient for genetic testing for EDS so it is not highly implausble or unrelated at all.

    ANother major and well known and highly respected ME/cfs specialist here with decades of experince specialising in ME - whose name i will PM you if you like - also has been know to tell patients that Me is due to "stretchy viens"


    best


    Ally
  2. Allyson

    Allyson *****

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    HI Shell

    so sorry to hear you have been feeling poorly, and thanks so muchfor the birthday wishes - much appreciated, esp as I have not been too well myself lately.

    It must be difficult caring for four children while you are that ill - let alone their problems too; my sympathies and admiration go out to you.

    (I have heard type 1 Diabeties is on the increase - dramatically so - and as for asthma the reasons are still unknown; hope they manage to find something useful soon for your son's sake - at least it is getting plenty of research.)

    Yes i agree, the research process is at least interesting and exciting at times.

    An yes , alas both diseases have been tragically overlooked and underresearched so far (except for brave few pioneers to whom we are grateful).

    My hope is that with the internet speeding up the pace of everythig including communication and the exponential potential of genetic and epigentic research things might soon change and we will have some answers. (An epigenitic based drug treatment has been developed for ventricular fibrillation which is a major breakthough - so there may still be a way for drug companies to make money from ME/EDS/OI/POTs etc.)

    BTW if anyone has or comes across an article on the occular manifastations of EDS - I thought it was posted here but it may have been another forum - would they mind reposting it or PM it to me please?

    Many thanks in advance..


    Best Allly
  3. Sushi

    Sushi Moderator and Senior Member Albuquerque

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    So what does referring a patient for genetic testing have to do with the premise that ME is due to EDS? A responsible doctor who detects signs of EDS in a patient who has not been diagnosed with EDS would most likely refer them for further testing to get a full clinical picture.

    A doctor would also refer a patient for TB testing if he/she saw indications of it. This doesn't mean that TB is related to ME.

    My ME specialist recognizes that I have EDS but he certainly does not think that EDS causes ME--he recognizes that I have two conditions.

    Sushi
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  4. ukxmrv

    ukxmrv Senior Member

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    The problem with no "naming names" is that it is not out on the open for people to comment on and share information. What is one patients "world known expert" is another's "Simon Wessely" (just using an extreme example to make the point clear)

    Just as an example and nothing to do with EDS.

    Dr Lloyd has had a long career with CFS in Australia. However, older patients remember him for his "it's not infectious" stance of the 90's also his fatigue clinic and exercise.

    So, there are opinions on doctors.
    Valentijn likes this.
  5. Kina

    Kina Moderation Team Lead

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    This comes from an EDS site:


    ME is not a collection of disorders that impact the connective tissues. Connective tissue defects do not cause the symptoms and signs of ME. I have read quite a few descriptions of ED from many sources. Whether it's six or ten subtypes, it still doesn't change that EDS is a connective tissue disorder with a genetic basis. It doesn't change the fact that EDS and ME share no major diagnostic criteria.

    Another site has these subtypes:

    Untitled.png

    These subtypes exemplify the differences between a ME and EDS diagnosis.

    Here are just a few examples of some of the research on EDS (I can provide more).

    Valentijn likes this.
  6. Allyson

    Allyson *****

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    Ritelli et al
    University of Brescia

    In text emphasis - bolding - is mine .... sorry no date for this abstract but there is an email address

    thanks Janet Kopacz for sending


    Clinical and molecular characterization of 40 patients with classic Ehlers-Danlos syndrome: identification of 18 COL5A1 and 2 COL5A2 novel mutations.

    Ritelli M, Dordoni C, Venturini M, Chiarelli N, Quinzani S, Traversa M, Zoppi N, Vascellaro A, Wischmeijer A, Manfredini E, Garavelli L, Calzavara-Pinton P, Colombi M.

    Source
    Division of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy. colombi@med.unibs.it.


    Abstract
    ... BACKGROUND:
    Classic Ehlers-Danlos syndrome (cEDS) is a rare autosomal dominant connective tissue disorder that is primarily characterized by skin hyperextensibility, abnormal wound healing/atrophic scars, and joint hypermobility. A recent study demonstrated that more than 90% of patients who satisfy all of these major criteria harbor a type V collagen (COLLV) defect.

    METHODS:
    This cohort included 40 patients with cEDS who were clinically diagnosed according to the Villefranche nosology. The flowchart that was adopted for mutation detection consisted of sequencing the COL5A1 gene and, if no mutation was detected, COL5A2 analysis. In the negative patients the presence of large genomic rearrangements in COL5A1 was investigated using MLPA, and positive results were confirmed via SNP-array analysis.

    RESULTS:
    We report the clinical and molecular characterization of 40 patients from 28 families, consisting of 14 pediatric patients and 26 adults. A family history of cEDS was present in 9 patients. The majority of the patients fulfilled all the major diagnostic criteria for cEDS; atrophic scars were absent in 2 females, skin hyperextensibility was not detected in a male and joint hypermobility was negative in 8 patients (20% of the entire cohort).



    Wide inter- and intra-familial phenotypic heterogeneity was observed. We identified causal mutations with a detection rate of approximately 93%. In 25/28 probands, COL5A1 or COL5A2 mutations were detected. Twenty-one mutations were in the COL5A1 gene, 18 of which were novel (2 recurrent). Of these, 16 mutations led to nonsense-mediated mRNA decay (NMD) and to COLLV haploinsufficiency and 5 mutations were structural. Two novel COL5A2 splice mutations were detected in patients with the most severe phenotypes. The known p. (Arg312Cys) mutation in the COL1A1 gene was identified in one patient with vascular-like cEDS.


    CONCLUSIONS:
    Our findings highlight that the three major criteria for cEDS are useful and sufficient for cEDS clinical diagnosis in the large majority of the patients. The borderline patients for whom these criteria fail can be diagnosed when minor signs of connective tissue diseases and family history are present and when genetic testing reveals a defect in COLLV. Our data also confirm that COL5A1 and COL5A2 are the major, if not the only, genes involved in cEDS.
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  7. Kina

    Kina Moderation Team Lead

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    Allyson -- do you know what confirmation bias is. Confirmation bias is a tendency of people to favor information that confirms their beliefs or hypotheses. So no matter what people say on this thread, it seems you will go out and find that one bit of evidence that you believe supports your position. Unfortunately, most of this evidence does nothing to confirm that ME and EDS are in any way diagnostically related. I am just assuming that your post was an answer to my previous post.

    This does not change the fact that EDS and ME do not share any major diagnostic criteria to even suggest they are related. Did these patients that didn't meet all the major criteria for EDS meet the diagnostic criteria for ME or were they simply difficult to diagnose patients? The authors state that difficult to diagnose patients with borderline symptoms can be genetically tested for EDS to confirm their diagnosis or to confirm a diagnosis of a connective tissue disorder. ME is clearly not a connective tissue disorder.
    This supports that EDS is a connective disorder with a genetic basis. As of yet, ME has no distinct genetic markers. What this study does not conclude is that EDS is related to ME. Minor signs of connective tissue disease, family history, and involvement of a specific gene are not in the diagnostic criteria for ME.

    The authors state in their conclusion:

    and

    The important comment would be that a genetic test can assist with the diagnosis of cEDS or hEDS or other connective tissues disorders. It also states that the diagnosis of cEDS can be confirmed with genetic testing. This study again exemplifies the fact that EDS and ME are distinct disorders with distinct diagnostic criteria. IF you read through the description of the subjects in this study, it is apparent that their signs and symptoms are quite distinct from ME. Yes, there are some overlapping symptoms but that is true for many disorders. It does show that EDS can at times be difficult to diagnose and that genetic testing will confirm a diagnosis for those with borderline symptoms.

    I think a more appropriate topic for this thread might have been discussing how some of the symptoms of ME and EDS overlap and the similarities and differences between the two. Rather than a discussion about how they are one and the same because they clearly are not. I am glad I read this thread because now I know something about a disorder that I previously knew very little about.
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  8. Allyson

    Allyson *****

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    Thanks to Janet Kopacz for this article - she comments
    This is an older article but found it interesting. I hae asked her for a date.
    Bold in text is my emphasis - ? unknown type of EDS.

    Obstetric and gynecologic dysfunction in the Ehlers-Danlos syndrome.
    Sorokin Y, Johnson MP, Rogowski N, Richardson DA, Evans MI.

    Source
    ... Department of Obstetrics and Gynecology, Wayne State University/Hutzel Hospital, Detroit, MI 48201.


    Abstract
    Women members of the newly formed Ehlers-Danlos National Foundation (EDNF) were surveyed with a very detailed questionnaire with 50 questions concerning family history and inheritance, past medical history, and obstetric and gynecologic problems. They entailed the largest extant database on Ehlers-Danlos Syndrome (EDS) patients. The mean age of the 68 women who responded to the survey was 42 years; most had EDS types I, III, IV and unknown. Forty-three women had 138 pregnancies; 13 women never married. The stillbirth rate was 3.15% (3/95); the preterm delivery rate was 23.1% (22/95), and the spontaneous abortion rate was 28.9% (40/138). There was a cesarean delivery rate of 8.4%, with 14.7% having perinatal bleeding problems. One woman (EDS type IV) had congestive heart failure. Common gynecologic problems were recurrent anovulation (41.3%), recurrent vaginal infections (53%), abnormal cytologic smears (19%), sexual dysfunction (61%), irregular menses (28%), endometriosis (15.8%), vaginal dryness (25%) and a need for hysterectomy (19.1%). In this largest series of pregnancies with EDS, we found relatively high rates of abortion, preterm delivery, pregnancy-related bleeding and stillbirth. Women with EDS also seem to have high frequency of anovulation, vaginal infections, abnormal cytologic smears and dyspareunia.
  9. dannybex

    dannybex Senior Member

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    Agree completely. Perhaps a new thread, with a new thread title...? But then again... :)
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  10. Allyson

    Allyson *****

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    Shell


    here is the article on occular matters and EDS - this one doesNOt mention cateracts sorry - cannot recall if there was nother that did now but iwll keep searchig for you..

    The impairment of lysyl oxidase in keratoconus and in keratoconus-associated disorders.

    Dudakova L, Jirsova K.
    ...
    Source

    Laboratory of the Biology and Pathology of the Eye, First Faculty of Medicine, Institute of Inherited Metabolic Disorders, Charles University and General University Hospital, Prague, Czech Republic.

    Abstract

    Keratoconus (KC) is an eye disease characterized by the progressive thinning and protrusion of the cornea, which results in the loss of visual acuity.

    This disorder remains poorly understood, although recent studies indicate the involvement of genetic and environmental factors. Recently, we have found that the distribution of the cross-linking enzyme lysyl oxidase (LOX) is markedly decreased in about 63 % of keratoconic specimens.

    Similarly, LOX activity is significantly reduced by 38 % compared to control tissue. Nearly 70 systemic disorders have been reported in association with KC, most of them affecting the extracellular matrix. In this review we attempted to ascertain whether any KC-associated diseases exhibit signs that may reflect LOX impairment.

    We hypothesized that very similar changes in the extracellular matrix, particularly at the level of collagen metabolism, including LOX impairment in mitral leaflets, may reflect an association between KC and mitral valve prolapse.

    Moreover, this putative association is supported by the high frequency of Down syndrome in both diseases.

    Among other disorders that have been found to coincide with KC, we did not find any in which the LOX enzyme may be directly or indirectly impaired.

    On the other hand, in cases where KC is present along with other connective tissue disorders (Marfan syndrome, Ehlers-Danlos syndrome and others), KC may not arise as a localized manifestation, but rather may be induced as the result of a more complex connective tissue disorder.


    best,

    Ally
  11. Kina

    Kina Moderation Team Lead

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    I have Keratoconus. You can actually see the bulges on my cornea from it. I get a lot of ghost images. Driving at night is not an option. This started when I was in my mid-twenties. It escalated for about 10 years and then evened out. My vision is quite poor and Keratoconus rules out having laser surgery and our stinking government won't pay for cross-linking surgery and I can't afford 5,000 dollars per eye. My grandmother had keratoconus. My mother has keratoconus. My sister has keratoconus. None of the males in our family have which suggests in our family that is is related to XX chromosome. I am the only person in my family that is ill. My sister does triathlons and marathons. She is very healthy. My mother is a very healthy 77 year old woman. My grandmother lived to a very healthy 95 years old with a bit of age related dementia near the end.

    It seems to be genetic disorder in my family's case as well as the fact that most of the females in our family are born without knuckles in their big toes. Keratoconus and the lack of knuckle issues doesn't seem to translate into ill-health or connective tissue disorders in our family.

    I doubt keratoconus is related to ME. I doubt it is even related to EDS. I have spoken to quite a few people with the condition and none of them have mentioned any symptoms of EDS.They all are healthy. I have had genetic testing and there are no genetic defects related to any collegen defects. I think I am correctly assuming that my keratoconus is part of the genetics of a female nature in my family and it is not related to ME/CFS as all the females in my family with KC are extremely and annoyingly healthy.
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  12. ukxmrv

    ukxmrv Senior Member

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    We are going around in circles. I suggested at the start that this thread should be renamed. These arguments were brought up at the start and I've seen no evidence that connects ME with EDS apart from the odd thing here and there and the (of course valuable) experience of individual patients.

    The title is misleading so people may be reading this because they think that there is evidence here. It is interesting though but a lot of the stuff on POTs I've already seen and it's been lost in the sheer volume.

    The general EDS stuff if going to be of interest maybe to those with the condition if they haven't already seen it but that's niche.

    I'm at a loss to see how a doctor could misdiagnose a person with pure EDS as CFS or ME but given the poor level of testing I've seen in the UK it doesn't come as a surprise.
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  13. dannybex

    dannybex Senior Member

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    I agree ukxmrv. I also agree with Kina, that some folks with CFS/ME may indeed develop SOME symptoms or signs of EDS, perhaps not the hyper mobility stuff, but rather collagen related issues. But that can happen with any long-term chronic disease or illness.
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  14. Sushi

    Sushi Moderator and Senior Member Albuquerque

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    Yes, several of us asked Allyson to rename the thread when it was first started and Allyson said that would be fine, but it didn't happen. That could have saved us all this circular posting.

    Sushi
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  15. merylg

    merylg Senior Member

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    http://www.molvis.org/molvis/v13/a130/

    Testing is available for the following genes involved in the TGFB/SMAD pathway:
    TGFBR1
    TGFBR2
    SMAD3
    TGFB2
    These are associated with Loeys-Dietz Syndrome, a connective tissue disorder, somewhat recently characterised. A study is soon to be published relating to allergy & immune issues in the earlier found types of LDS.

    Disruption of the TGFB/SMAD pathway is associated with cancer.

    http://ghr.nlm.nih.gov/gene/TGFB2

    http://omim.org/entry/614816

    I'm planning to start by testing SMAD3, as that seems relevant to my own issues. Testing is sooo expensive, but costs are coming down all the time.

    I see a definite connection here with immune problems, and have no problem with this thread, even if the title is provocative.


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  16. Allyson

    Allyson *****

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    Thanks Merylg yes and we have nothing to lose by thinking about it; for my part i am about to start testing for Lyme - I will try anything really that does no harm and I do not think i have it but would liketo rule it out.

    Yes i have heard of Loeys-Dietz - its name often crops up in connection with EDS so i believe there is some definite link - as there is with Marfans. (My grandfather had Marfan's habitus ( I realise only now)- a build like Ted Danson - tall long libs hard to put on weight.)


    As for genetic testing though it is not really there yet for most types of EDS I am told.
    The gentics clinic at Royal Melbourne Hospital - one of Australia's best and it is a department of Melbourne University in effect - did not even test me though they thought my symptoms matched - they said they would need to test for severl hundred genes - 300 - 400 i think - at the moment; if each text is several hundred dollars it would hardly be worth it (they did not say the cost was the issue though - that is my guess). But as you say costs are plummetting quickly.

    But he said definitely watch this space and come back in 2 years as things are happening so quickly.

    I think the Human Genome Project will feed into it and as more people narrow down there symptoms and start looking to be diagnosed with the help of the internet and present to doctors - especially research geneticists - ie those associated with Universities and research - the more interst will be garnered.


    And hopefully research will accelarate..

    Best of luck with your testing though ... would love to hear updates thanks.

    cheers

    Ally
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  17. GcMAF Australia

    GcMAF Australia Senior Member

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    Considering that several people who previously had been diagnosed with Sarcoidosis now have been diagnosed with Lyme Disease and at least 24% of Autism cases had antibodies to Lyme -->
    Then it is quite feasable that other diseases have a Lyme association.

    Many people seem to be misdiagnosed with MS etc etc
    and Quote Allyson
    Doctors and patients rarely make the connection that many different complaints are coming from one problem.
    I Hope that this helps!!
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  18. Allyson

    Allyson *****

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    HI GcMaf,

    thanks indeed that is useful.

    More incentive for me to chase up the testing quickly.

    I will book for the Aussie tests tomorrow then follow up with the overseas ones if that is negative.

    And potentially tratable is a plus.

    Yes I agree there is still so much to sort out with all these illnesses.

    Thanks again for the helpful input.


    Ally
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  19. Shell

    Shell Senior Member

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    Allyson Thanks I'll have a read of that.
    With my 10 year old I have had two main ideas about where his cataract came from; first is my use of codeine for pain when I was pregnant. It was during my preg with him that I became ill. The pain was off the wall.Despite docs insisting that my baby wouldn't be effected he had terrible codeine withdrawal not long after birth. And the other idea I had was Coxsackie B because that was the virus from the big Scottish cluster and I discovered a paper saying Coxsackie can cause fetal cataracts.
    One thing against that is I am pretty sure R's cat started a little after his was born.
    on EDS - he does have very translucent skin, and as I've said I have two girls who can lick their noses with glee (especially my most unladylike 6 year old).

    My other query about ME is the automimmune one as my oldest son has type 1. but that's for another time and another thread I think.
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  20. GcMAF Australia

    GcMAF Australia Senior Member

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    There is a victorian Facebook site for Lyme people
    There are about 6-7 children in Victoria that have Lyme and "autism"
    1 is improving with treatment
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