In honour of Ehlers-Danlos Syndrome awareness month (May) I created a daily fact series on my Instagram @StrongerThanPots. This week I thought I'd share all of those facts in one place so they can be easily accessed for future reference, and shared to spread awareness. As referenced on the pictures, I used many sources for the information provided below. The most frequently quoted source is The Ehlers-Danlos Society.
Ehlers-Danlos Syndrome Fact 1:
Ehlers Danlos Syndrome (EDS) is an inherited disorder.
Ehlers-Danlos Syndrome is an inherited connective tissue disorder. Connective tissue is the glue that holds everything in your body together. Having Ehlers-Danlos Syndrome is like being held together with gum instead of crazy glue. Each of the 13 Ehlers-Danlos Syndrome subtypes differ significantly in symptom presentation and exact genetic cause. However, all subtypes "are generally characterized by joint hypermobility, skin hyperextensibility, and tissue fragility." -The Ehlers-Danlos Society
Ehlers Danlos Syndrome Fact 2:
Ehlers-Danlos Syndrome isn't a new condition!
"People with lax joints and multiple scars were first described in the medical writings of Hippocrates, dating back to 400 BCE. In 1892, Dr. A. Tschernogobow, a Russian dermatologist, presented 2 case studies of patients to the Moscow Venereology and Dermatology Society who had marked loose fragile skin, ad hypermobile joints. His work reports the first detailed clinical description of EDS." -Medscape (Defendi, 2017)
Ehlers-Danlos Syndrome Fact 3:
Ehlers-Danlos Syndrome affects a lot more than just joints and skin!
“The connective tissue a person with EDS is built with is not structured the way it should be. With a badly-constructed or processed connective tissue, some or all of the tissue in the EDS-affected body can be pulled beyond normal limits which causes damage. Connective tissue can be found almost anywhere, in skin, muscles, tendons and ligaments, blood vessels, organs, gums, eyes, and so on." -The Ehlers-Danlos Society
Ehlers-Danlos Syndrome 4:
How to diagnose EDS!
To determine a diagnosis of Ehlers-Danlos Syndrome, your doctor will use the Beighton Scale to assess joint hypermobility, review your family history and personal medical history, look for abnormal scarring, feel the elasticity of your skin, and often perform genetic testing. When reviewing your personal medical history, your doctor will determine whether you have the major and minor symptoms required for a diagnosis of EDS.
These major and minor symptoms differ per subtype and are sometimes referred to as the Brighton Criteria (the Beighton Scale is included in this set of symptom criteria). Since there is significant symptom overlap between each different subtype, genetic testing is used to confirm the diagnosis in all cases besides Hypermobile Ehlers-Danlos Syndrome.
Ehlers-Danlos Syndrome 5:
There are 13 Ehlers-Danlos Syndrome subtypes.
“The 13 identified subtypes are Classical EDS (cEDS), Classical-like EDS (clEDS), Cardiac-valvular EDS (cvEDS), Vascular EDS (vEDS), Hypermobile EDS (hEDS), Arthrochalasia EDS (aEDS), Dermatosparaxis EDS (dEDS), Kyphoscoliotic EDS (kEDS), Brittle Cornea Syndrome (BCS), Spondylodysplastic EDS (spEDS), Musculocontractural EDS (mcEDS), Myopathic EDS (mEDS), and Periodontal EDS (pEDS). All subtypes, besides Hypermobile EDS, have a known genetic mutation.”
Ehlers-Danlos Syndrome Fact 6:
A problem in connective tissue can create countless issues.
"An analogy: If one builds a house with faulty materials, say half the necessary wood or with soft aluminum nails, it is certain there will be problems. Some problems are more likely to show up than others, but because those materials were used everywhere and are not necessarily visible, one can be surprised by where a problem shows up or how serious it is. It is much the same thing with an Ehlers-Danlos Syndrome and connective tissue." -The Ehlers-Danlos Society
Ehlers-Danlos Syndrome Fact 7:
Ehlers-Danlos Syndrome is a common cause of Dysautonomia.
Not only can Ehlers-Danlos Syndrome cause a lot of symptoms and complications in and of itself, but it's also known to cause other illnesses with their own symptoms and complications. Exact statistics are hard to determine, but one study found that orthostatic hypotension, POTS, and uncategorized orthostatic intolerance were found in 78% of those with Hypermobile EDS (Gazit, 2003).
Ehlers-Danlos Syndrome Fact 8:
Subtype: Classical Ehlers-Danlos Syndrome (cEDS)
The major criteria for cEDS are skin hyperextensibility, poor wound healing, and joint hypermobility. Minor criteria include smooth velvety skin, molluscoid pseudotumours, subcutaneous spheroids/spherules, complications of joint hypermobility, muscle hypotonia, delayed gross motor development, easy bruising, manifestations of tissue extensibility and fragility, surgical complications, and a positive family history (Bowen, 2017). cEDS also has known cardiovascular, oral, ocular, gastrointestinal, and pain and neurological involvement.
Genetics: The causative mutation in cEDS is COL5A1 or COL5A2. cEDS is inherited in an autosomal dominant pattern and, therefore, those with EDS have a 50% chance of passing on cEDS in each pregnancy.
Ehlers-Danlos Syndrome Fact 9 Subtype:
Classical-like Ehlers-Danlos Syndrome (clEDS)
Classical-like EDS is a rare form of EDS characterized by skin hyperextensibility and joint hypermobility like Classical-EDS but without the cEDS wide scars. The major criteria are 1. skin hyperextensibility with velvety skin texture and without atrophic scarring, 2. generalized joint hypermobility, and 3. easily bruised skin or discolorations of the skin resulting from bleeding underneath (The Ehlers-Danlos Society). Long thin fingers, swollen legs, nerve compression syndrome, flat feet, diverticular disease and wasting of the muscles in the hands and feet also appear to be unique to clEDS (Patient Info).
Genetics: TNXB is the only gene associated with clEDS. clEDS is inherited in the autosomal recessive pattern which means that you need to inherit one faulty gene from each parent. If a parent only has one clEDS gene mutation, they generally will not have the condition themselves.
Ehlers-Danlos Syndrome Fact 10:
Subtype: Cardiac-valvular EDS (cvEDS)
Cardiac-valvular Ehlers-Danlos Syndrome is a rare subtype of EDS characterized by severe cardiac-valvular problems (of the aoritic or mital valve), skin hyperextensibility, thin skin, atrophic scars,easy bruising, and joint hypermobility. cvEDS patients often require surgical interventions due to the severe defects found in their aorta (NORD & The Ehlers-Danlos Society).
Genetics:"cvEDS is caused by a complete lack of the proa2-chain of type I collagen due to biallelic COL1A2 mutations, that lead to nonsense-mediated mRNA decay. COL1A2 is the only gene associated with cvEDS." -The Ehlers-Danlos Society
Ehlers-Danlos Syndrome Fact 11:
Subtype: Vascular Ehlers-Danlos Syndrome (vEDS)
vEDS is characterized by "family history with documented causative variant in COL3A1, arterial rupture at a young age, spontaneous sigmoid colon perforation in the absence of known diverticular disease or other bowel pathology, uterine rupture during the third trimester in the absence of previous C-section and/or severe peripartum perineum tears; and carotid-cavernous sinus fistula (CCSF) formation in the absence of trauma" (The Ehlers Danlos Society). On top of these 5 major criteria, there are 12 minor criteria for this rare subtype. Genetics: vEDS typically caused by "a heterozygous mutation in the COL3A1 gene, with the rare exception of specific heterozygous arginine-to-cysteine substitution mutations in COL1A1 that are also associated with vascular fragility and mimic COL3A1-vEDS. In very rare instances, biallelic pathogenic variants in COL3A1 may be identified. Vascular EDS is inherited in the autosomal dominant pattern." -The Ehlers-Danlos Society
Ehlers-Danlos Syndrome Fact 12:
May is Ehlers-Danlos Syndrome (EDS) awareness month, but May 12th is also international Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome Day (ME/CFS).
These two conditions share more than just an awareness month though! Castori (2011) found that 82.6% of those with Hypermobile Ehlers-Danlos Syndrome also met the criteria for Chronic Fatigue Syndrome (ME/CFS). Doctors are unaware of the exact cause of the CFS/ME and EDS comorbidity, but The Ehlers-Danlos Society has said that "some people with CFS likely have EDS that has not been identified."
Ehlers-Danlos Syndrome Fact 13 Subtype:
Hypermobile Ehlers-Danlos Syndrome (hEDS)
A diagnosis of hEDS is only made in the presence of all 3 major criteria which includes: 1. generalized joint hypermobilitiy 2. two or more of the features listed below (A & B, A & C, B & C, or A & B & C), and 3. All criteria met with the absence of abnormal skin fragility and other connective tissue or autoimmune rheumatologic disorders. Features for the 2nd major criteria include Feature A: systemic manifestations of a more general connective tissue disorder (a total of five out of twelve must be present), Feature B: positive family history, with one or more first degree relatives independently meeting the current diagnostic criteria for hEDS, and Feature C: musculoskeletal complications (must have at least one of three)" (The Ehlers-Danlos Society).
Genetics: Hypermobile EDS is known to be inherited in the autosomal dominant pattern, but it is the only subtype of EDS without a known genetic cause at this time.
Ehlers-Danlos Syndrome Fact 14:
There is a lot of debate about the similarities and differences between Hypermobile Ehlers-Danlos Syndrome (hEDS) and what was formerly known as Joint Hypermobility Syndrome (JHS).
What once was termed Joint Hypermobility Syndrome (JHS) or Hypermobility Syndrome (HMS) is now termed Hypermobility Spectrum Disorder (HSD) according to the Hypermobility Syndromes Association (HMSA). A diagnosis of Hypermobility Spectrum Disorder (HSD) is given when a person's hypermobility causes symptoms but they do not have a diagnosis of EDS or Marfan syndrome (HMSA).
Some doctors believe that HSD is undiagnosed hEDS. Others believe that Joint Hypermobility Disorders appear on a spectrum that range from asymptomatic Joint Hypermobility (JHS) on one end, to Hypermobile Ehlers-Danlos Syndrome (hEDS) on the other.
Ehlers-Danlos Fact 15:
Subtype: Arthrochalasia EDS (aEDS)
Arthrochalasia EDS is a rare subtype of EDS characterized by Congenital bilateral hip dislocation, severe joint hypermobility with the presence of dislocations and subluxations, and skin hyperextensibility (The Ehlers-Danlos Society). The minor criteria include muscle hypotonia, kyphoscoliosis, mild osteopenia, tissue fragility (with atrophic scars), and easily bruisable skin (EDS Today).
"aEDS is caused by heterozygous mutations in either COL1A1 or COL1A2, that cause entire or partial loss of exon 6 of the respective gene. No other genes are associated with aEDS" (EDS Today). aEDS is inherited according to the autosomal dominant pattern.
Ehlers-Danlos Syndrome Fact 16:
Subtype: Dermatosparaxis EDS (dEDS)
The 9 major criteria for dEDS are "1. extreme skin fragility with congenital or postnatal skin tears, 2. characteristic craniofacial features, which are evident at birth or early infancy, or evolve later in childhood, 3. redundant, almost lax skin, with excessive skin folds at the wrists and ankles, 4. Increased palmar wrinkling, 5. severe bruisability with a risk of subcutaneous hematomas and haemorrhage, 6. umbilical hernia, 7. postnatal growth retardation, 8. short limbs, hand and feet, and 9. perinatal complications due to connective tissue fragility" (NIH). There are also 11 minor criteria for dEDS.
dEDS is an autosomal recessive disorder. "dEDS is caused by biallelic mutations in ADAMTS2" (The Ehlers-Danlos Society).
Ehlers-Danlos Syndrome Fact 17
Subtype: Kyphoscoliotic EDS (kEDS)
The 3 major criteria for kEDS are 1. congenital muscle hypotonia, 2. congenital or early onset kyphoscoliosis, and 3. joint hypermobility with both dislocations and subluxations in the shoulders, hips, and knees (The Ehlers-Danlos Society). kEDS has 11 minor criteria and 4 specific criteria associated with the PLOD1 gene mutation and 4 for the FKBP14 mutation (The Ehlers-Danlos Society).
kEDS is an autosomal recessive condition. "The majority of patients with kEDS harbor biallelic mutations in PLOD1; recently, biallelic mutations have been identified in FKBP14 in patients displaying a phenotype that clinically largely overlaps with kEDS-PLOD1" (The Ehlers-Danlos Society).
Ehlers-Danlos Syndrome Fact 18:
Subtype: Brittle Cornea Syndrome (BCS)
BCS has 4 major criteria including 1. thin cornea (with or without rupture), 2. early onset progressive keratoconus, 3. early onset progressive keratoglobus, and 4. blue sclerae. There are also 14 minor criteria.
"BCS is caused by biallelic mutations in either ZNF469 or PRDM5. At least one family with a clinical BCS phenotype did not harbor mutations in these genes, suggesting that at least one other gene might be associated with BCS. Brittle cornea syndrome is inherited in the autosomal recessive pattern" (The Ehlers-Danlos Society).
Ehlers-Danlos Syndrome Fact 19:
Subtype: Spondylodysplastic EDS (spEDS)
The 3 major criteria for spEDS are 1. short stature, 2. muscle hypotonia, and 3. bowing of limbs. Other common symptoms of spEDS are flat feet, intellectual or learning disabilities, skin hyperextensibility, eye issues, characteristic facial features ("triangular face, wide-spaced eyes, bulging eyes, narrow mouth, low-set ears, sparse scalp hair, flat face, wide forehead, blue sclerae, abnormal teeth, and cleft palate/bifid uvula, thin curly hair, sparse eyebrows and eyelashes, loose elastic skin on the face"), etc. (NIH).
spEDS is an autosomal recessive condition. The 3 major criteria listed above are accompanied by 5 minor criteria, in addition to specific criteria for the gene mutations in B4GALT7, B3GALT6, and SLC39A13.
Ehlers-Danlos Syndrome Fact 20:
Subtype: Musculocontractural EDS (mcEDS)
Typical signs of mcEDS include 1. characteristic craniofacial
features (seen since birth), 2. congenital multiple contractures (adduction-flexion contractures and/or "club foot"), 3. characteristic cutaneous features (including fine palmar creases), 4. peculiar finger shapes, 5. large, recurring subcutaneous hematomas (in the skull, extremeties, or hips), 6. progressive spinal and foot deformities, and 7. ophtalmological and urogenital involvement (Brady et al., 2017).
"Musculocontractural EDS is caused by biallelic mutations in CHST14. A few mutations have been identified in the DSE gene in patients with a similar phenotype. Musculocontractural EDS is inherited in the autosomal recessive pattern" (The Ehlers-Danlos Society).
Ehlers-Danlos Syndrome Fact 21:
Subtype: Myopathic EDS (mEDS)
mEDS is a rare form of EDS that has been found in only 9 patients from 5 different families. mEDS is known to cause muscle weakness in infancy that tends to improve with age. The 3 major criteria for mEDS are 1. Congenital muscle hypotonia and/or muscle atrophy, 2. Proximal joint contractures, and 3. Hypermobility of distal joints (The Ehlers-Danlos Society).
Genetics: "mEDS is caused by heterozygous or biallelic mutations in COL12A1, and the clinical phenotype highly overlaps with collagen type VI-related myopathies. It is currently unknown whether other, yet to be discovered genes, are associated with this phenotype. In case no COL12A1 mutations are identified alternative diagnoses, especially collagen VI-related Ullrich Congenital Muscular Dystrophy and Bethlem Myopathy, should be considered. mEDS is inherited in either the autosomal dominant or the autosomal recessive pattern" (The Ehlers-Danlos Society).
Ehlers-Danlos Syndrome Fact 22:
Subtype: Periodontal EDS (pEDS)
The 4 major criteria of pEDS include "1. Severe and intractable periodontitis of early onset (childhood or adolescence); 2. Lack of attached gingiva; 3. Pretibial plaques; and 4. Family history of a first-degree relative who meets clinical criteria" (The Ehlers-Danlos Society).
pEDS is an autosomal recessive condition "caused by heterozygous gain-of-function mutations in C1R or C1S. At present it cannot be stated whether absence of a C1R or C1S mutations excludes the diagnosis because the experience with the molecular diagnosis is limited" (The Ehlers-Danlos Society).
Ehlers-Danlos Syndrome Fact 23:
A new EDS subtype has been discovered!
Blackburn1 et al. discovered a new, incredibly rare subtype of Ehlers-Danlos Syndrome in February 2018. This subtype has only been found in 4 people from 3 unrelated families. The specific gene mutation found is responsible for symptoms similar to other forms of EDS including "joint laxity, redundant and hyperextensible skin, poor wound healing with abnormal scarring, osteoporosis, and other features." (The Ehlers-Danlos Society). This subtype has not yet been classified or named but will most likely be considered the 14th in the next official classification.
Exome sequencing found variations in the AEBP1 gene which is a gene responsible for the collagen between cells (The Ehlers-Danlos Society). This new subtype of Ehlers-Danlos Syndrome is inherited according to the autosomal recessive pattern.
Ehlers-Danlos Syndrome Fact 24:
Some doctors think pursuing a diagnosis of EDS is pointless because it doesn't have a cure.
However, this is inaccurate and ignorant for several reasons. EDS can cause many multi-system complications and an accurate diagnosis of EDS can ensure specialists know what to look out for. Knowing you have EDS doesn't only give you the knowledge of what complications to look out for, but the knowledge in how to prevent some. For example, those with all types of EDS are more prone to DVTs, aneurysms, and cerebral hemorrhage. Knowing this can empower you to use preventative measures when flying and avoid certain medications. An accurate diagnosis of EDS can also help you with future family and career planning.
Ehlers-Danlos Syndrome Fact 25:
Connective tissue serves to connect other tissues.
Through the process of Decellularization, here you can see the connective tissue that surrounds the heart. This powerful image has been used to demonstrate how important and prevalent connective tissue is throughout our body. Those with Ehlers-Danlos Syndrome have defects in connective tissue and can therefore experience countless symptoms.
Ehlers-Danlos Syndrome Fact 26:
Current treatment for EDS focuses on minimizing pain and symptom management.
Treatment options include physiotherapy, pain medication, surgical intervention to repair damaged joints, high-dose vitamin C supplementation, and symptom management. There is no known cure for any of the Ehlers-Danlos Syndromes. Although most subtypes of EDS are not fatal in and of themselves, EDS can cause many possible mild to life-threatening complications.
Ehlers-Danlos Syndrome Fact 27:
Ehlers-Danlos Syndrome is a recognized rare disorder.
All EDS subtypes are considered rare disorders at this time, but some are more rare than others. Some subtypes affect 9 known people worldwide (mEDS) while others affect 1 in 250,000 (vEDS). Classical EDS, Hypermobile EDS, and Vascular EDS account for 79% of EDS patients (CCSO, 2015). The combined prevalence of all the Ehlers-Danlos Syndrome subtypes is approximately 1 in 2,500-5,000 people. However, exact prevalence rates are unknown because of how frequently misdiagnosed EDS is.
Ehlers-Danlos Syndrome Fact 28:
Many people with EDS identify as "medical zebras."
In Medical School, students are often taught "when you hear hoof beats, think of horses not zebras." Simply put, these future doctors are told to think of the most common explanation for a patient's symptoms. This perspective is used to promote efficiency but unfortunately often leaves patients with rare conditions, like Ehlers-Danlos Syndrome, dismissed and misdiagnosed. As Professor Rodney Grahame once said, "no other disease in the history of modern medicine has been neglected in such a way as Ehlers-Danlos Syndrome."
Ehlers-Danlos Syndrome Fact 29:
EDS is a multisystem disorder that often requires many different specialists to treat.
An accurate diagnosis of Ehlers-Danlos Syndrome is most commonly done by a geneticist. However, doctors of all specialties can be trained to recognize the signs of Ehlers-Danlos Syndrome. Patients with EDS often see doctors from a variety of specialists due to the wide range of symptoms experienced. It is also recommended that patients with EDS see an Ophthalmologist and Cardiologist annually to ensure that EDS is not affecting the eyes and heart. Many EDS specialists also recommend that a bone density test be done on patients every few years to ensure that EDS is not affecting the patient's bones.
Ehlers-Danlos Syndrome Fact 30:
Ehlers-Danlos Syndrome can be an extremely painful condition!
Although Ehlers-Danlos Syndrome symptoms can be mild in some cases, many patients experience excruciating pain. EDS is most commonly known for its joint hypermobility, subluxations, and dislocations, but EDS can also cause muscle pain and weakness, migraines, nerve pain, secondary arthritis, and several other painful conditions.
"At this point in time, I put EDS in the category of being in the top 3 or 4 most severe pain problems. A lot of people for example, think that cancer pain is the worst of pain. But let me assure you that many EDS patients have pain far beyond any cancer patient I've ever seen." -Dr. Forest Tennant, 2015.
(I don’t like comparing pain and conditions, but since everyone knows how awful cancer is, this helps paint a picture of what EDS can look like. Of course not all EDS patients experience the 3rd worst pain at every single second, although some do! Some people with EDS may experience this intensity of pain in waves, while some may experience a more mild version. Either way, EDS can be a very painful condition!
Ehlers-Danlos Syndrome Fact 31:
The average time between a patient's initial onset of symptoms and receiving an accurate diagnosis of EDS is 19 years!
19 years of pain and suffering, 19 years of being passed between specialists, and 19 years of being dismissed and minimized. This is completely unacceptable. We can do better, we must do better!
"If you can't connect the issues, think connective tissues!"
You can be part of the solution! Please consider donating to Ehlers-Danlos Syndrome organizations like "The Ehlers-Danlos Society". When you donate to a rare disease organization, your money goes a long way. You're investing in hope!
I hope you enjoyed this fact series and learned so