Ehlers-Danlos syndrome and autism

This is one in a series of blogs where I discuss different conditions manifesting autstic symptomatology of known origin or neuropathology (so-called syndromic autism). The first of these blogs was on tuberous sclerosis (http://bit.ly/17ExHYt ). The emphasis in all of these blogs is in the commonality of abnormalities in certain parts of the brain.  It is my belief that in autism there is a common lesion that interferes in some way with the division of germinal cells early during brain development. The end result is abnormalities in cell migration and malformed areas of the cerebral cortex and brainstem. You can find additional information about this process at:  http://bit.ly/1aM5KFu and http://bit.ly/136db0t In this blog I discuss the Ehlers-Danlos syndrome and some commonalities to idiopathic autism primarily in terms of brain pathology.

The Ehlers-Danlos syndrome (EDS) is a group of inherited conditions that affect the connective tissues of the body. As the name implies, connective tissue serves to “connect” or join together different parts of an organ. In doing so, connective tissue provides support to the organ and gives it its distinctive shape. Some specialized types of connective tissue, provide more than support, and play a significant functional role for the body, e.g., adipose or fat, cartilage, blood. Considering both the large variety of connective tissues and the fact that they can be found almost anywhere in the body, it is unsurprising that disorders of connective tissue are very common (think of anemia, arthritis, or even obesity).

tissue_connective

There are over 200 recognized connective tissue disorders of multiple causation. Ehlers-Danlos syndrome belongs to a small group of connective tissue disorders that are genetic in origin. Other inherited connective tissue disorder that manifest autistic symptomatology include Marfan’s and the Lujan-Fryns syndromes. People with a Marfanoid physical appearance (i.e., tall with long extremities- see figure), absence of the corpus callosum and mental retardation usually have the Lujan-Fryns syndrome. Approximately 90% of patients with the Lujan-Fryns syndrome exhibit some type of mental symptomatology, the most common of which is autistic behaviors. Tantam et al. (1990) reported 3 cases of Asperger syndrome with a Marfanoid appearance. Some case reports mention patients with the dual diagnosis of  Ehlers-Danlos syndrome and autism (Fehlow et al., 1993) and the relationship has been expanded upon in a communication by Sieg (1992). EDS and autism share comorbidities like irritable bowel syndrome (arguable), sensory integration disorders, and anxiety disorders.

marfan

In Ehlers Danlos syndrome a number of different mutations affect a protein called collagen. This is the most common protein found in the human body, accounting for 25 to 35% of the whole body protein.  The gelatin used in the food industry is a type of collagen that has been altered in a chemical reaction with water.

Ehlers-Danlos syndrome is seen in approximately 1 out of every 5,000 people within the general population. It affects the connective tissue of the joints, blood vessels and skin providing for loose/flexible joints (as in double-jointed individuals), fragile blood vessels (bleeding) and stretchy skin that bruises easily. Symptoms vary in severity across patients. Some individuals, having a “vascular type” of the condition, may suffer from life threatening complications like spontaneous rupture of blood vessels and bowels.

People with EDS may have abnormal brain development because matrix proteins (as seen in germinal tissue) and those related to cell attachment are affected. Migrational abnormalities may be common with heterotopias (misplaced cluster of cells) being reported in some cases (Cupo et al., 1981). There are now several case reports in patients diagnosed with Ehlers-Danlos syndrome relating nodular brain heterotopia to seizures and dyslexia. Since neurons fail in their migration to the cortex, the same may be malformed, exhibiting patches of abnormal convolutions (polymicrogyria). The brainstem and cerebellum may also be affected and patients are usually born with portions of their cerebellum protruding through a large opening in the occipital bone (foramen magnum).  This type of abnormality is called a Chiari type I malformation.

Ehlers-Danlos

Figure: Clusters of cells fail in their migratory attempt out of the periventricular germinal zone and remain behind as nodules impinging on the wall of the ventricles (so-called candle gutterings). Similarities between this finding and that reported in autism can be judged from a coronal cut in a postmortem specimen shown in http://bit.ly/136db0t

In previous blogs we have mentioned how the proposed pathology for autism predisposes the same to cortical hyperexcitability.  The explanation has been used to suggest a mechanism capable of explaining the presence of seizures, sensory problems and headaches. The analogy to migraine headaches was dealt in http://bit.ly/14h1THp  It is therefore of interest the conclusions of a study: “Individuals with EDS may be prone to migraine due to an inherent disorder of cerebrovascular reactivity or cortical excitability” (Jacome, 1999).

In conclusion, Ehlers Danlos is another cause of syndromic autism.  The pathology exhibited in the brains of individuals with EDS suggests a migratory defect of germinal cells early on during gestation. This is the same type of abnormality that we have proposed in idiopathic autism. This commonality among a very large number of conditions giving rise to syndromic autism seems more than a coincidence and deserves further investigation.

References

Cupo LN, Pyeretz R, Olson J, McPhee S, et al. Ehlers-Danlos syndrome with abnormal collagen fibrils, sinus of Valsalva aneurysms, myocardial infarction, panacinar emphysema and cerebral heterotopias. Am J Med 71:1051-1058, 1981.

Fehlow P, et al. Early infantile autism and excessive aerophagy with symptomatic magalocolon and ileus in a case of Ehlers-Danlos syndrome. Pediatric Grenzgeb 31:259-267, 1993.

Jacome DE. Headache in Ehlers Danlos syndrome. Cephalagia 19():781-6, 1999.

Sieg KG. Autism and Ehlers-Danlos syndrome. Journal of the American Academy of Child and Adolescent Psychiatry 31:173, 1992.

Tantam D. Evered C, Hersov L. Asperger’s syndrome and ligamentous laxity. Journal of the American Academy of Child and Adolescent Psychiatry 29:892-6, 1990.

45 responses to “Ehlers-Danlos syndrome and autism

  1. I would slightly quibble with your definition of the syndrome as an inherited syndrome. The NIH clains that half the cases are caused by a de novo gene mutation.

    http://www.ncbi.nlm.nih.gov/books/NBK1244/

    ‘Genetic counseling. EDS, classic type is inherited in an autosomal dominant manner. It is estimated that approximately 50% of affected individuals have inherited the disease-causing mutation from an affected parent, and approximately 50% of affected individuals have a de novo disease-causing mutation. Each child of an affected individual has a 50% chance of inheriting the mutation. Prenatal testing for pregnancies at increased risk is possible for families in which the disease-causing mutation has been identified in an affected family member’.

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  2. You are correct that Ehlers Dnalos Syndorme Hyper Mobility type is inherited. The is the least severe manifesation of the syndrome and unlike the more severe classic syndrome parent to child transmission does occur:

    http://www.ncbi.nlm.nih.gov/books/NBK1279/

    ‘Disease characteristics. Ehlers-Danlos syndrome (EDS), hypermobility type is generally considered the least severe type of EDS, although significant complications, primarily musculoskeletal, can and do occur’.

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    • It is misleading to classify Hypermobility Type as the “least severe” form of EDS (as you quoted, even the NIH hedged their statement with “generally considered”). The mischaracterization likely stems from the fact that Hypermobility Type is much more common than the others, and since the range of severity varies widely across types, there are many more people with mild Hypermobility Type running around than there are people with mild Classical Type.

      In regards to the previous commenter (Bob Jensen), all forms of EDS may either be inherited, or be the result of a spontaneous mutation. Although the rate of new manifestations varies across types, it’s estimated to be as high as 50% on average.

      And keep in mind that the nosology is very imperfect, and it’s generally understood that practically *no* EDS patients fit neatly inside any one type!

      Anywho, a very interesting article; thank you for it!

      Liked by 1 person

    • People can apparently have more than one type (I would imagine this would happen if each parent had a different type and passed on the relevant gene(s) ). There is also sufficient overlap between some types that unless a genetic test is undertaken, specific type misdiagnosis can occur. HEDS can be extremely severe, there is a lot of generalisation in some of these comments. It is also multi-systemic meaning someone can be very debilitated. I know because I live it!

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  3. I agree with what you are saying. In tuberous sclerosis (the previous blog) an even higher percentage, about two thirds of cases, are the results of de novo mutations. Still it is considered an inherited condition.

    My mind would go in a tangent trying to explain a somewhat different phenomenon: how can a condition be highly heritable (the results of a genetic mutation that causes a particular phenotype) ….but not inherited (passed on to progeny)! In some conditions the phenomenon may be due to the fact that patients, for any given reason, do not reproduce. Many of the conditions that we are dealing with (being described in my blogs) are either de novo mutations, follow a two-hit model, or patients, for some reason, may not reproduce.

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  4. I am extremely interested in the link between EDS and Autistic Spectrum Disorder – my 6 year old has recently been diagnosed with EDS, but was originally taken to the paediatrician with suspected ASD. As his parent (and registered nurse) I am still in ‘discussions’ with the specialist about my son’s ASD symptoms, as these are unresolved and I have suspected that there is a link between this and EDS. Can you provide further journal article references for this connection please? I would be most grateful.

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    • Besides the Sieg reference mentioned in the blog you may try Takei et al.High functioning autistic disorder with Ehlers-Danlos syndrome. Psych Cln Neuroscience 65(6):605-6, 2011. I was not able to acquire the same through pub med or other services, so I did not quote it in my blog.Let me know if I can be of any further help.

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  5. My son 20 yrs old has EDS- hyper mobility type and we have been told there is a strong possibility he has PDD-pervasive developmental disorder,atypical autism, in other words asbergers syndrome. I had always known something was “not quite right” as he aged yet diagnosis took much TOO LONG! At birth he had congenital esotropia (severely cross-eyed) and beginning at 8 mos of age until the present, opthamalogists have done extensive work; including surgeries, patching, eye drops, different focal eyewear. As heartbreaking as it was nothing was working! As time passed and he grew older, dyslexia and using unilateral vision rather than binocular vision followed. But, little did we know this was just the beginning 😦
    More to follow if this sends

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    • I truly empathize. The story of your son is similar of others that I have received regarding EDS and autism. Not coincidentally I have written several other blogs about dyslexia. Thank you for sharing.

      As an aside, I will be leaving work this Friday for a couple of weeks (attending 2 conferences). I may not be able to answer any emails or commentaries to the blog during this period of time.

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  6. Well, I have Asperger’s and EDS (hypermobility type). Both my children have ASC and my youngest has a diagnosis of hypermobility, my eldest has clear signs (backwards pointing elbows for one) but has not been assessed. Clearly both conditions are genetic in our cases. I strongly suspect I may have Chiari Malformation too, as I also have Klippel-Feil Syndrome and have many of the symptoms for Chiari. All these conditions are known to be linked.

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    • I can’t offer a mechanistic explanation as to how a Chiari malformation, Klipper-Feil syndrome, EDS and ASD are related- but related they are. I have tried to publicize this combination in different blogs. Hopefully it will raise awareness within the medical profession. Thank you so much for your comment.

      Liked by 1 person

      • Awareness desperately needs raising. Both my ASC and EDS diagnoses were made privately following incompetent NHS assessments of both conditions which failed to diagnose. It’s a sad day when the patient is better informed than the supposed diagnosticians. Will follow your blog with interest.

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    • Thank you. Just noticed that you had reblogged the entry. Physicians don’t have it on their minds and are likely to miss the diagnosis over and over again. My experience is that when a diagnosis is made it is brought to the attention of the physician by the patient.

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      • Yes, I think the training compared to the science is way behind. The trouble is, doctors treat symptoms in isolation without joining the dots and patients can end up therefore mis-treated. Medicine needs to become more holistic. I now find out I have PoTs (Postural Orthostatic Tachycardia Syndrome) which frequently goes with EDS. But many people with PoTs/EDS are treated as if it’s CFS/ME, “all in the mind” or other things. The way many doctors are, there is a disrespect for patients/an arrogance against patients, and if a patient attends a consultation having researched and well-informed lots of doctors don’t like this. This can result in erroneous opinions of hypochondria, attention-seeking and in the UK when you couple that with great resistance to spending money on referrals, can leave many in misery with untreated conditions.

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      • I certainly agree. I wrote a recent blog trying to emphasize a more humanistic side to medicine (http://bit.ly/1EO3yLL) when considering the neurodiversity debate. I also called to attention the disrespect and arrogance of the medical profession. Please note that the peril of treating symptoms in isolation without connecting the dots is about to increase exponentially in the near future with the advent of the so-called “precision medicine”. I think this movement will be catastrophic for those with ASD. If you don’t get the expected laboratory values (all being genetic) you will certainly be deemed a hypochondriac. –You have certainly given me the idea for my next blog on Precision Medicine. Thank you very much.

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  7. Pingback: End of the year summary | Cortical Chauvinism·

    • The average time that a patient gets to tell his/her side of the story before being interrupted by the physician is 30 seconds. I have always been distressed by the statistic.

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      • It may be more appalling. The 30 seconds time frame is what I was told in a lecture a long time ago. In looking over at conducted studies, the time span may be even less, some 12 to 18 seconds. Th reference can be found by following the links: http://bit.ly/16Ecx3p

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      • A good blog and certainly an impressive website with associated resources. I took a look around and specially liked the tonal frequency in the home page.

        I am not a computer person as reflected in my blog site (very simple) and I never have a lot of time to write or review my blogs. Hopefully they will get better.

        I always like meeting like-minded individuals.

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      • Thank you. The frequency is apparently the “miracle” or “love” tone which heals DNA (http://attunedvibrations.com/528hz-dna-repair/), known as Solfeggio or Fibonacci numbers (in case you weren’t aware of this). You can read a bit more here http://themindunleashed.org/2014/03/miracle-528-hz-solfeggio-fibonacci-numbers.html, they aren’t my websites BTW, it’s just what I discovered during my surfing. Even if you don’t subscribe to the proclaimed abilities of 528 Hz it’s still feel-good music. (A bit of an Aspie tangent there!). Don’t be over-impressed by the “bells and whistles” on mine (I just wanted to make it an immersive experience!), it’s all about what the blogs themselves say, and yours are really intelligently written. Research is a bit of a special interest of mine hence I usually find loads of links…which may have the effect of diverting traffic from my website ultimately but it isn’t about self-aggrandisement it’s about spreading awareness so it doesn’t matter if they find that on mine or elsewhere.

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      • I will try recreating the music with my frequency generator. I can use sine waves which provides fairly pure tones with no harmonic distortions. For a long period of time I truly wanted to be either an electronic engineer or a mathematician. Life guided me in a different direction. Now that I am getting into age, I feel happy that I did follow medicine as I have been able to help many people -probably in my third stage of Hindu philosophy. Now my hobbies are my grandchildren, the blog, and going back to electronics.

        Thank you for saying that my posts are intelligently written. I really don’t spend that much time on them.I have found that the ones that take a longer time become lyrical rather than scientific. I have a clear tendency for hyperbole, metaphors and obscure references that need to be kept in check.

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    • “I have a clear tendency for hyperbole, metaphors and obscure references that need to be kept in check.” An Aspie’s antithesis! 😉 It’s good to read things that stretch the mind and thanks for your kind words. Do you mean a blog repost (like a WordPress ‘reblog’ – or posting the link to one) or a guest blog? Let me know what angles you are looking for and if/when I come up with something, I will email you. Like you, I tend to sometimes get a spark of an idea from things when someone says something, or a situation arises that I feel the urge to speak about. It can be very sporadic (depending on how bogged down I am with life, as both my children are autistic too and my responsibilities sometimes overtake me).

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      • I would be honored to have you write a guest blog using one of your sparks. –I have four daughters. One has dyslexia, another extreme ADHD (inattentive type), and another an autoimmune condition that has played with both her life and self-esteem. My first grandchild is syndromic autistic (first case reported of an obscure mutation). Still very grateful for all life has given me.

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      • And I would be honoured to write one too. My youngest has undiagnosed co-morbid ADHD, I am sure of it, as you know it’s often co-morbid with autism. I’ve had a struggle to get recognition of this with professionals, because, as with autism, my research has identified that girls with ADHD don’t present the same as boys and often go undiagnosed, so there is no formal diagnosis for her. Self-esteem is I think, often affected with all of these conditions unfortunately.

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  8. Thank you for this! I was diagnosed with EDS Hypermobility type last June (finally!) and autism spectrum condition on Monday (again, finally!) and complex PTSD last April (related to autism too due to higher ‘normal’ levels of anxiety and an increased vulnerability)… I’m 27 and I think our eldest may have both too (he is 10) but the services here are poor. We have just been blocked by two pathways to diagnosis, so back to the gp to seek further assistance, if that fails I will be contacting the NAS for support because the poor kid is so misunderstood it really makes me sad I can see him going through the same things I did. On the bright side he is male so the hormones he is starting to experience should help him build muscle and improve his joints as opposed to the female hormones I have experience of.

    Fortunately the youngest seems neurotypical so far, certainly her social skills are better than mine aready (she’s only two). But her joints do click a little. Hopefully she will grow out of it and be ‘normal’. I am so sad I got my diagnoses after having children. It would have been nice to have the chance to decide if the risks of passing my problems on we’re worth it or not, but I suppose they are here now and all I can do is my best.

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  9. Hola
    Tengo diagnóstico de Ehlers Danlos tipo hipermovilidad y me interesa mucho el tema del SED, como se lo conoce en español, con posibles porblemas cognitivos, y de personalidad. Los trastornos cognitivos es algo que he notado en mí dislexia discalcúlia, incapacidad para ubicarme en el tiempo y espacio, incapacidad para las funciones ejecutivas y todas las que requieran grabarse procesos y desarrollarlos vez tras vez y poca capacidad organizativa. esto afecta mucho mi vida adulta y he llegado a pensar incluso que sufro de algún tipo de retraso cognitivo, esto me frustra mucho porque a más de las limitaciones que me proporciona el SED, está la aparte cognitiva y me niego a aceptar también una limitación cognitiva, pienso que mi inteligencia está bien y que a pesar de que las cosas que mencioné se me dificultan, soy muy buena por ejemplo en el plano artístico, claro, tomando en cuenta de que el arte no está bien remunerada como la informática o la contabilidad, esto afecta mucho el desempeño laboral y la consecuente retribución económica puesto que lo una persona que se desarrolla en el área artística rara vez tiene una retribución económica igual o superior que alguien que se dedica a tareas que tienen que ver con números, procesos, función ejecutiva y capacidad organizativa. En fin, me gustaría mucho saber si hay estudios específicos que indiquen una clara relación entre Ehlers Danlos y porblemas cognitivos, no importa que esté en inglés, tengo amigos médicos que pueden ayudar en la traducción.
    Gracias

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    • No tengo referencias y una pequena revision de la literature no me revelo nada extraordinario. Este en realidad no es mi campo pero creo que puede haber una relacion entre SED y problemas cognitivos aunque la misma no se haya descrito o haya sido poco estudiada.

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  10. I was diagnosed with Ehlers Danlos Hypermobility type in January of 2013 at the age of 46. My eldest will be 30 in July (I’m 49 now). He was diagnosed with Asperger Syndrome at the end of Junior High. He’s always had sensory issues and difficulties, which made school more difficult. His joints have started popping now but he has never shown the degree of hypermobility that I have, so I’m hoping he doesn’t end up with as much pain as I deal with now. My youngest is 24 and was born with a spina bifida occulta that was diagnosed at about 18 months of age. He shows no signs of Asperger but has also started dislocating joints. The Dr at the local ER didn’t believe that he had dislocated his knee. This was before I’d ever heard of EDS, so we had no idea that the knee could have been dislocated and gone back in on it’s own. Both seem to be physically stronger than I am, as I’m disabled now and need to use a walker or a cane. I remember having some symptoms of AS but learned how to work around them. It does not surprise me at all that these are likely related. I just wish more research would be done to help catch all of this earlier. When I worked at a human service agency, I remember lifting boxes and doing things that likely made my issues worse. I also have POTS and likely have a mast cell disorder. Both boys seem to have allergies but not chronic urticaria like I do, so I’m hopeful on that front too. I’m glad we stopped at two. Thank you for the great blog on this issue.

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    • That you for your comments. Your story illustrates how these conditions are linked together. Hopefully the blog along with testimonials, such as yours, will bring more awareness to the public and to medical professionals.

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  11. Given the length of time during which mutations for the vast majority of EDS Hypermobility cases have been searched for and not found, I personally think it’s most reasonable to conclude that EDS Hypermobility comprises largely epigenetic illnesses, not genetic. Being able to reverse some symptomology, so that I am stronger and healthier at 60 than 40 despite EDS Hypermobility has encouraged that thought, in my case.

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  12. I can’t agree more about this comorbidity of autism and EDS based on personal albeit unscientific observation of thousands online and hundreds off line in my EDS community. I really appreciate the neurologists insight into it also. (I’ve been saying we have saggy hindbrains! Not so much large ones as Temple Grandin describes but saggy.) But just as with EDS, I feel like doctors and patients only recognize the grossest signs of the rarest types (i.e, the most “clinical” forms) of both conditions (as well as other common comorbidities). But considering we’re all likely mildly (or more) Aspie, with lots of B&W thinking, and this is no surprise! You can read my observations of same here: http://ohtwist.com

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    • Thank you for your comments. I tried to publicize this relationship as it appears to be unrecognized by most physicians. Most to the shame of the medical community many times patients bring this correlation to them instead of the other way around. -As an aside, I also translated the blog to Spanish for this reason.Wish I could translate it into other languages as well.

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  13. Given I have one child with severe mutile autism and one girl with EDS this is familiar to me .
    Their father had a more mild aspergers and EDS . They have had 3 tesla MRI s that exactly
    Corroborate what you are saying . As a family of doctors I am working on a paper about it .
    It is more obvious to the people that live with it on a daily basis . It is far from the genetic speculation of the Bureaus that you mention .

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    • Thank you for the comment and for trying to help publicize such a relationship. I have traveled far and wide and in my question and answer sessions I usually find somebody who describes the phenotype presented in this blog. It is much much much more than a simple coincidence.

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  14. My son has asperger’s and diagnosed Marfan or “Probable Marfan” though he has many signs of EDS. I am diagnosed with “some type of connective tissue disorder” and believe I have EDS. Geneticists we’ve seen say there is no correlation with autism and connective tissue disorders, but I’ve seen way too many on support groups online who have both.

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    • I have been trying to publicize this relationship but have met with resistance from the general medical community. Hopefully as more and more patients come forth, the relationship will be clear. Thanks for your comment.

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  15. I have Ehler-Danlos and Aspergers. I believe they are related. My boyfriend is a psychologist who recently sent one of his autistic patient’s to a doctor to be evaluated for Ehler-Danlos because of the symptoms I have. The patient did in fact have Ehler-Danlos. I believe there has to be some sort of connection between them.

    Liked by 1 person

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