Diagnosing EDS and HSD

March 20th, 2017: Oof – this whole post just got nearly obsoleted entirely by the BRAND new ginormous EDS nosology (classification) and diagnostic criteria, which now replace BOTH the old Villefranche nosology AND the Brighton (with an “r”, not “e”) Diagnostic criteria.

But NOT the Beighton (with an “e”!) 9 pt hypermobility scale (or score) which was just part of the Brighton diagnostic criteria in a plot to confuse -that is still in use -for now. (Phew! Confusing!)

And we have a brand new category of Hypermobility Spectrum Disorders (HSDs) to diagnose now too!

Thanks for your patience while I continue updating my site. And please refer to this site via the international Ehlers-Danlos Society  for the ultimate answers as they are dictating the rules. I urge downloading the 18 classification papers here now. 

Note for doctors May 2018: The EDS Toolkit for General Practitioners originally produced and hosted by the Royal College of General Practitioners in May 2018, is now hosted by EDS UK since January 2022. Any doctor that is willing can technically diagnose the new HSDs and all forms EDS, but especially the most common form: hypermobile EDS (hEDS). It’s just that few are willing as yet. But please be sure to do proper full differential diagnosis! (See below for more on that.) You have my sympathy with the process. I fear the Toolkit above makes it all seem a little too simple, when in fact, it’s not if you do full proper differential diagnosis.

Some may still wish to refer more distinct or unusual cases to the geneticist and probably should. But the new nosology and the toolkit above were designed specifically to ease the burden on medical genetics offices. (Personal note: I was honored to be tapped by the project lead as a contributing author based on this blog and my Twitter stream.) Read on for a more in-depth description.

ETA 10/30/24: I just learned of a retired geneticist, Dr. Golder Wilson in Texas who feels you do not need genetic testing to diagnose any form of EDS. That testing is not that accurate: you can have a SNP but not show signs of the matching disease. And vice-versa: show signs of a form of EDS, but not have the matching SNP for that form. This matches what I’ve heard from other geneticists in the past. But, You can go for testing if you really want, and especially if you do strongly suspect vascular EDS (vEDS). (See below for more on that.) You can also get help from him to be diagnosed remotely now. (He’s retired.) Keep this in mind as you plow through the following.

Last updated October 30, 2024

13 Types of EDS Newly Defined in 2017

Since it’s often so hard to get a doctor or doctors to listen to us and recognize our vast collections of symptoms as a possible systemic condition, we naturally want an easy test to take and be done with this painful journey. Our often ADHD brains and over-worked doctors want this too, natch.

Well, I’m sorry to break it to you, but there is no single test for ALL of the types of Ehlers-Danlos Syndromes yet.

And as of March 2017 the old diagnoses of HMS, JHS and BJHS have all been supplanted by both the new hEDS and HSD classification per The Ehlers-Danlos Society (TEDS). Not all doctors are up to date nor on board with this for various reasons. Direct questions to TEDS at info@ehlers-danlos.com. See also Road to 2026.

Update 10/1/24: We’ve just become aware that there is a single gene panel now available to run when a doctor suspects one or more of the rare genetic forms of EDS, (currently 12 of the 13 types recognized in 2024) versus needing to pick just one or two and run them separately. Check out the 34 minute mark of this podcast interview with Dr. Alan Hakim in 2024 for more on that. NB It is not meant to just be run for any- and everyone, but when you do suspect one or more truly rare forms EDS with known genetic markers. (ETA 10/30/24: Though Dr. Wilson in Texas still doesn’t think that’s truly necessary, but you can if you really want to.)

And there is no single tissue marker or genes identified yet to test for the most common type of EDS, known as hypermobile EDS or hEDS (formerly known as Type III EDS). Which The Society still insists on calling rare since they invented the Hypermobility Spectrum Disorders for all those who fail the hEDS checklist, though several of us beg to differ. However…

Additional update 10/1/24: We bring exciting news of a POTENTIAL biomarker just recently published in September 2024 that may be able to help diagnose hypermobile EDS (hEDS) and HSD in the future! This study still needs to be replicated and a commercial test developed, but the finding is quite distinct, and of course quite exciting after so many years of gaslighting and confusion for hEDS and HSD patients. (Stay tuned.)

Yes, whole genome (WGS) and whole exome sequencing (WES) tests are coming way down in price and thus in reach for more patients at just $1000 or less. But, this is not a practical move. You end up with seriously overwhelming heaps of unnecessary data to weed and sort through, and the bench research to match it with is still not there.

I.e, you may have many interesting Variants of Unspecified Significance, or VUS’s, but no one may know what to do with them yet. Science needs a chance to catch up. Same goes for WES testing still too, though it is just a subset of your genome too. Please talk to a geneticist if you insist on doing this. (Dr. Hakim addresses this also in this podcast after the 34 minute mark.)

History of EDS Nosology and Diagnosis

There were six main types of EDS recognized until March 14th, 2017, but several one-off mutations in single families around the world with new ones found periodically. There are now 13 total types formally recognized as of March 2017, up from the former six main types prior. In May 2018 a really rare autosomal recessive gene was announced but not yet named or folded into the nosology. And possibly one other I’m missing here. (This will keep happening over time.)

And at least two more candidate genes to explain some cases of hEDS have been uncovered since 2023 (MIA3 and Kallikrein), though testing is not available for these yet, and they are also not yet part of the 2017 nosology. I’m sure more genes are waiting in the wings to be announced soon too, thanks all of you dedicated scientists and researchers. (See Road to 2026.)

Five of those six former types were considered rare, but now all thirteen formally recognized types of EDS (as of 2017) are considered rare by TEDS again based on the new criteria, and twelve of the thirteen now have known genetic markers. Only the most common type, hypermobile EDS, aka “hEDS” does not – yet.

SPOILER ALERT: Hypermobility Spectrum Disorders are a diagnosis of exclusion of ALL of the above, plus ALL other similar connective tissue diseases like Marfans, Loeys-Dietz, Sticklers, etc. So there is no genetic test for it. It’s a clinical diagnosis, still, period. (As of 10/1/24.) But ONLY AFTER PROPER FULL DIFFERENTIAL DIAGNOSIS is done!

In other words, you have to diligently and thoroughly rule out ALL OTHER POSSIBLE FORMS OF EDS OR OTHER CTDs based on history and presentation. THEN you may diagnose a form of HSD. Not the other way around. Yes, that’s upwards of 20+ conditions to wade through. Again, my sympathies.

Suggested Diagnostic Flow Chart

1a – Do they seem like they have some kind of CTD?	1b – Gather as much medical history as you can to see (I recommend using a spreadsheet)
2a – Rule out all rare forms of EDS with genetic markers (12 of 13 as of 2024) if suspected	2b – There are 12 types with markers per the 2017 nosology here
3a – If negative by testing for those, then rule out all other possible similar CTDs like:	3b – Marfans, Loeys-Dietz, Stickler Syndrome, Osteogenesis Imperfecta, Cutis Laxa
4a – If negative for those, then rule out hEDS	4b – No genetic test yet*, see hEDS Diagnostic Checklist
5a – If negative for hEDS, then diagnose a form of Hypermobility Spectrum Disorder	5b – This is a diagnosis of exclusion of ALL THE above!

Diagnostic Issues

As noted, the most common type by far still, hypermobile EDS or hEDS as it’s called now (formerly “Type III”) does not have a genetic or biomarker yet, so it can only be diagnosed clinically still using the new 2017 diagnostic criteria for it.

Nota Bene March 2017: The criteria for hEDS were tightened a good bit, and the entirely new category of Hypermobility Spectrum Disorders or “HSD” was proposed and adopted to catch the rest of us who show some hypermobility, but no longer meet these new criteria. (You may be very bendy, but not have enough issues with your tissues to pass, or have lots of systemic trouble, but not be flexible or bendy enough to pass the hEDS criteria.) The Ehlers-Danlos Society welcome feedback on this via Road to 2026.

So I will now refer to all forms of EDS as rare again, but I personally do not consider the HSDs  to be, just rarely recognized still and no, not just because they’re new. But because patients’ complaints keep being dismissed as mine were for 25 years due to misinformation and misunderstanding about how common the condition is.

And no, you cannot diagnose yourself via your raw data from 23andMe or Ancestry etc., contrary to rumors in many online support groups.

These are likely finding nonsense mutations or non-pathogenic single point mutations aka “SNPs” that aren’t known disease-causing mutations. Further, there can be other kinds of pathological mutations (duplications, deletions) that you can’t uncover this way.

Not all SNPs cause disease or trouble just because they are on a gene of interest (e.g. ADAMST2, PLOD1 etc.), some are just variations from the wild type, period, like hair color. You wouldn’t say brown-haired people have a hair disease for instance, right? The bench research needs to catch up. Please work with a medical doctor (ideally a geneticist) for proper diagnosis if you truly suspect a rare form of EDS, or similar connective tissue disease. (Marfans, Stickler’s, Osteogenesis Imperfecta, Charcot-Marie Tooth, Loeys-Dietz.)

Few doctors will take such a self-diagnosis seriously, nor should they. One geneticist I know has found errors in his patient’s 23andMe data after running WES on them later. And the second-party data interpreters (LiveWello, Genetic Genie, etc.) are not known for accuracy for another thing.

I’ve also gotten conflicting results from my own raw data after downloading and parsing it through the same third-party parser at different times. One time said I had a particular defect, the other time said I didn’t. From the same identical unaltered zip file. Which one is correct? I may never know. But I don’t think I should medicate or diagnose based on such questionable info! To quote Dr. Ben Lynch, “treat the person, not the SNP“, always.

Please do consult a qualified doctor if able to get the most accurate and complete diagnosis while ruling out other similar Heritable Connective Tissue Diseases (HCTDs) and other similar or secondary conditions while we continue tracking down more causes of hypermobile EDS. You might look for a local support group to help find the knowledgeable doctors in your region.

Hypermobility, often mis-interpreted to mean flexibility by most people itself is just a trait, like red hair color, and in itself is generally benign. It is thought to run in about 20 – 40% of the general population and lends nicely to gymnastic and dancing and singing careers.

The EDS and now also the HSDs all involve hypermobility plus symptoms, or issues like fallen arches, bad teeth, tendinitis, hernias, easy bruising, varicose veins and so much more that ultimately drive you to see the doctor a lot for those who aren’t in denial.

The New Diagnostic Pathway since 2017

Update March 20, 2017: The Brighton Diagnostic criteria are now gone, and supplanted by these now.  On a good note, we will no longer have to deal with the confusion between the Beighton (with an “e”) 9 pt hypermobility scale or score, and the Brighton (with an “r”) diagnostic criteria (which included the Beighton scale), which no one ever kept straight! (Including me.)

Some types of EDS are autosomal dominant, including vascular EDS (vEDS). And hEDS is still being defined. Further study is warranted and eagerly sought! And, I’ve heard that upwards of 40% of vEDS cases can be de novo (new) mutations or cases in a family in a plot to further confuse us all.

But other forms are autosomal recessive, so are even more rare, thankfully. Both parents would have to carry the same recessive gene for a child to express the defect also which by Punnet Square math happens only 1 in 4 times (or a 25% chance) even then.

And again, this does not preclude an occasional rare “de novo” (new) mutation unknown to science yet that might spring up in a family on rare occasion. As well as other forms of mutations (copy number variants, deletions, duplications, etc.) Though I’ve yet to meet anyone who truly did not show a family history once we delved deeply enough and I enlightened them further to the MANY manifestations of EDS, but the possibility does exist, however rare. (Hey, someone has to be the first case of something, right? This actually happened to a young friend of mine.)

First, Suspect a Connective Tissue Disorder

I highly recommend my When to Suspect and When Else To Suspect EDS and HSD pages for starters. Obviously, it helps if you can gather biological family history, but this is not always possible. (Some of us are adopted, others disowned or abandoned or our family is not cooperative.)

Fill out a spreadsheet if you can

Here is a sample spreadsheet for helping to gather some of your relevant family history in a fixed, unmodifiable sample PDF Here. This is just a starting example I developed, you can create your own using a spreadsheet program like Excel or Google documents as well. (October 2018 editor’s note: There used to be another great pre-diagnostic medical workup page linked from The Coalition Against Pediatric Pain here too, but it seems to have been deleted, sorry!)

Your geneticist will love you for this if you get to see one, as it really helps them to see patterns in your family history. I would fill one out one for each side of your family, as able. (E.g. one for mom’s, one for dad’s side, if known. List yourself and your siblings both times.)

If you do suspect a rare type, this may also help you get a referral to a geneticist if needed for proper diagnosis. And if not, it will help any willing doctor to diagnose you together. Don’t despair if you lack family history though. While quite helpful, lack of family medical history and living family members to examine should not stop a good diagnostician from succeeding.

And it’s okay if you can’t record or capture everything from everyone. (Don’t get hung up on achieving perfection.) Just record and note what you can as best you can. E.g. I was never more grateful for my late father’s unending family stories, despite gaps in my memory. Many family members were already gone, and others not speaking to me. Those stories helped me fill my sheet out just the same, greatly aiding my geneticist in 2012. (I had barely one month to do this, too.)

Do proper differential diagnosis

Unfortunately, you are stuck wading through the descriptions of all of the 12 rare types of EDS with known genetic markers one by one to become acquainted with their hallmark traits, to know if you should suspect one. As well as signs of the similar connective tissue disorders to also rule out like Marfans, Loeys-Dietz Syndrome, Stickler Syndrome, Osteogenesis Imperfecta, and more. (So yeah, upwards of 20 or more conditions, sorry.) Some of these traits include things like:

• club foot/feet
• bilateral hip dysplasia (aEDS)
• extremely stretchy or wrinkly skin (dEDS)
• distinct hypertrophic or atrophic scarring, or keloid scars (several types)
• extremely thin skin that tears easily (vEDS and cEDS and clEDS)
• blue sclerae in the eyes (vEDS and or cEDS)
• extreme scoliosis or kyphosis (all types can have mild) (kEDS)
• keratoconus (droopy corneas lending to astigmatism)
• uterine or other hollow organ ruptures or family history of same (vEDS)
• family history of early death from aneurysms, easy bleeding or organ ruptures (vEDS)
• Severe, early-onset periodontitis and or detached gingiva (pEDS)
• Short stature with muscle hypotonia and or contractures (spEDS)
• Aortic root dilation (especially in children – get a baseline) (several)
• Widely spaced eyes, bifid uvula, cleft palate, malar hypoplasia, and blue sclerae (Loeys-Dietz)
• Pectus excavatum or carnatum (sunken or pigeon chest) – (Marfans and Loeys-Dietz)
• Long slender fingers and or toes, marfanoid habitus (arm span to body length ratio) – see Marfans
• Lens dislocations – see Marfans
• Tortuous arteries and or veins and bleeding issues plus hypermobility – see Loeys-Dietz
• Extreme osteoporosis and or broken bones from an early age with little force – see Osteogenesis Imperfecta (please check for this as well as hypermobility in all suspected child abuse cases TY)

THIS LIST IS NOT COMPREHENSIVE. It is just meant to give you an idea of some unusual signs to watch for. If someone is just hypermobile with generalized joint pain, some subluxations and or dislocations, easy bruising, some easy bleeding, IBS, headaches and myopia, but none of the above, they probably have either hEDS or an HSD. (Both diagnoses of exclusion of all the other types and similar CTDs.) But please do proper thorough workup and differential diagnosis! Many cases of hastily diagnosed hEDS and HSD are turning out to be something else. And this may well affect treatment and prognosis, as well as epidemiology (statistics).

Diagnosing Hypermobile type EDS (hEDS) and Hypermobility Spectrum Disorders

Once you’ve ruled out all the more distinct rare forms of EDS and other HCTDs as described above, you are then left to diagnose the most common type of EDS by far known as hypermobile EDS or hEDS, clinically only via a thorough physical exam using these new criteria.

And if the patient is not bendy enough, or doesn’t pass those, then one of the forms of Hypermobility Spectrum Disorders should be assigned now as previously mentioned.

In other words, the Hypermobility Spectrum Disorders are a diagnosis of exclusion of ALL of the forms of EDS, and hypermobile type EDS (hEDS) is a diagnosis of exclusion of all of the other more rare, genetically-based forms of EDS as well as of all other similar Heritabler Connective Tissue Diseases (Marfans, Stickler’s, OI, Loeys-Dietz, etc.)

I like to think of the forms of EDS as the tip of the iceberg, easily visible above the water line and thus more easily diagnosed, and the new Hypermobility Spectrum Disorders are the vast majority that are less visible to the medical eye below the water line that we have just now recognized is there.

Diagnosing Vascular EDS (vEDS) in particular

Ehlers-Danlos of all types runs across all races/ethnicities. But thanks to more visible blue veins showing under their more “see-through” white skin, almost everyone with pale or lighter brown skin wonders at some point if they don’t have vascular EDS (vEDS, formerly Type IV), a dangerous rare form that lends to more shortened life spans than most from arterial or inner organ rupture. NB – vEDS can run in any race or ethnicity, not just white or Caucasian people.

Few of us will have vEDS, thankfully, but if you have enough other signs like a family history of vascular or internal organ ruptures under age 40 or aneurysms as shown here from the UW Collagen Diagnostic Lab who perform the testing for it, definitely rule it out:

“1. Possible diagnosis of EDS type IV: The vast majority of probands in families with this form of EDS are identified on the basis of a major complication either bowel perforation or vascular aneurysm or rupture. The International Ehlers-Danlos Foundation Advisory Board set the following guidelines for determination of the clinical diagnosis of EDS type IV. DNA-based testing is recommended for those who meet these guidelines. Note, however, that individuals with nonsense mutations of COL3A1 are less likely to have similar physical characteristics. The clinical diagnosis of EDS type IV is highly suspected when two major diagnostic criteria are present:

Major clinical diagnostic criteria:

• Intestinal rupture
• Arterial rupture
• Uterine rupture during pregnancy
• Family history of the vascular type of EDS

Minor diagnostic criteria alone are not sufficient to warrant the diagnosis unless identified in an individual with a major criteria.

• Thin, translucent skin (especially noticeable on the chest/abdomen)
• Easy bruising (spontaneous or with minimal trauma)
• Characteristic facial appearance (thin lips and philtrum, small chin, thin nose, large eyes)
• Acrogeria (an aged appearance to the extremities, particularly the hands)
• Hypermobility of small joints
• Tendon/muscle rupture
• Early-onset varicose veins
• Arteriovenous carotid-cavernous sinus fistula
• Pneumothorax/pneumohemothorax
• Chronic joint subluxations/dislocations
• Congenital dislocation of the hips
• Talipes equinovarus (clubfoot)
• Gingival recession”

“Proband” is genetic speak for “person presenting now” (I.e, the patient), vs their parents or children. I actually had vascular and kyphoscoliotic types ruled out based on a history of an ascending aortic aneurysm (or AAA) in my dad, skin and facial features, severe scoliosis in my aunt from birth, keratoconus, visible veins, and small joint involvement among other things. I was relieved to learn I was negative for both, and we settled on EDS-HT (now hEDS) for my diagnosis in 2012.

But that doesn’t mean I don’t still watch for issues, and I had a baseline echocardiogram done to rule out any aortic root dilation (common in us), or mitral valve issues, and watch for aneurysms.

Concluding notes

To be sure, there’s nothing very benign about hEDS aside from not dying directly. People with hEDS and the HSDs still end up mitigating plenty of serious issues, including severe dysautonomia, weak necks and spines lending to CNS issues, sciatica, spondylolysthesis (slipped vertebrae), Chiari malformation and more. (Including anaphylaxis from commonly comorbid Mast Cell issues.)

Further, although EDS types generally run “true” within a family, meaning if your parent has vEDS, you will get vEDS (if you do), it is possible to have more than one type of EDS coexisting in one person, even if it’s rare. I know one patient with both a rare form of EDS AND Marfan Syndrome, both confirmed with genetic testing. Talk about winning the genetic lottery!

But generally EDS will run true to type, meaning, if your contributing parent has classical EDS, you will inherit that form, and not kyphoscoliotic EDS, unless careful medical history or testing reveals another form from the other side of your family or you have a rare de novo mutation in your family. You probably can’t have more than two types though, as this may not allow for a fetus to be viable.

No, these conditions are no cake-walk, though yes, as I’m slowly but steadily proving along with many other hardy survivors that you can recover to some extent through dedicated nutritional & dietary work and tailored “zebra-friendly” (core-building) physical therapy that avoids injuring us further, and strengthening the bits we can.

Lastly, I’ll note that having EDS itself, as comprehensive as it is, does NOT preclude having other diseases, conditions or issues (aka comorbidities), simultaneously. As Hickam’s Dictum states: “patients can have as many diseases as they damn well please!” And I mean beyond the incredible list of ones I’ve already noted are fairly common in the community (thyroid issues, autism, depression, CVID, allergies, insomnia, chronic fatigue, fibromyalgia, etc.)  You may have any number of other illnesses and genetic disorders in addition, also.

As someone else unknown to me brilliantly said, EDS is as individual as fingerprints, and we are all unique individuals in addition especially when you toss in environmental factors which influence our epi-genetics, a whole other layer affecting genetic expression. So while we may share some common “themes” of dysautonomia, fatigue, pain and hypermobility, it will truly express absolutely uniquely within individuals even within the same family. This is known as variable expression. To borrow another phrase from the Autistic community: if you’ve seen one Ehlers-Danlos (or HSD) patient, you’ve seen one Ehlers-Danlos (or HSD) patient!

But as you know I feel strongly, every doctor has seen HSD if not also EDS patients whether they know it or not. Heck, we’re the frequent flyers in their offices by default! In fact, everyone has seen an HSD or EDS patient whether they know it or not, we’re that common IMHO. Hopefully the doctors will start spotting us a bit sooner with this information I’m sharing. (Nurses too!) I hope the above has helped to clarify how best to pursue a diagnosis once you do suspect it.