Genetics and Ehlers-Danlos Syndrome

For some people, joint pain, hyperflexibility, skin fragility, and vascular issues are a daily battle.  A group of disorders of connective tissue, called Ehlers-Danlos Syndromes, causes changes in the way that collagen forms in the joints, ligaments, and skin.

This article explores the research on Ehlers-Danlos syndrome and explains the genetic mutations that cause some of the subtypes of the disorder. You can check your genetic data (23andMe version 5 data) and learn more about how collagen disorders affect people.

Ehlers-Danlos Syndromes – connective tissue disorders

Ehlers-Danlos syndromes (EDS) are a group of genetic disorders impacting the connective tissues in the body.

Ehlers-Danlos was first described by two dermatologists, Edvard Ehlers and Henri Danlos, in the early 1900s. In the 1940s, it was named and categorized formally.

In 2017, the Ehlers-Danlos Syndrome International Consortium categorized 13 different subtypes and the criteria for diagnosis. Previously, the Berlin and Villefranche nosologies were used to describe several subtypes of EDS.

As you can see below, the different EDS subtypes are defined by the genetic mutation the person carries — with one exception, hypermobility EDS is diagnosed without any genetic testing.

Table adapted from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786113/

Subtypes Notable features Gene(s) involved Structural effect of disorder
Classical EDS Skin fragility, hyperextensibility
Atrophic scarring
Joint hypermobility
Common joint dislocations
Easy bruising
Hernia
COL5A1
COL5A2
Rarely COL1A1
Affects primary structure and processing of collagen
Classical-like EDS Skin fragility, hyperextensibility
Joint hypermobility
Common joint dislocations
Easy bruising
Foot deformities
Peripheral edema
Mild muscle weakness and atrophy
Polyneuropathy
Organ prolapse
TNXB Affects myomatrix structure and function
Cardiac-valvular EDS Joint hypermobility
Skin hyperextensibility
Severe defects of cardiac valves
Hernia
Pectus deformity
COL1A2 Affects primary structure and processing of collagen
Vascular EDS Aneurysm, dissection, or rupture of arteries
Perforation or rupture of gastrointestinal organs
Rupture of the uterus during pregnancy
Skin translucency
Easy bruising
Distinctive facial features
COL3A1
Rarely COL1A1
Affects primary structure and processing of collagen
Hypermobile EDS Joint hypermobility
Velvety/soft skin
Slightly hyperextensible skin
Common joint dislocations and subluxations
Chronic pain
Causative gene unidentified in most cases
Arthrochalasia EDS Severe joint hypermobility at birth
Congenital dislocation of bilateral hips
Skin hyperextensibility
Atrophic scarring
COL1A1
COL1A2
Affects primary structure and processing of collagen
 Dermatosparaxis EDS Extreme skin fragility and laxity
Delayed closures of fontanels
Distinctive facial features
Blue discoloration of the sclera
Short fingers and stature
ADAMTS2 Affects primary structure and processing of collagen
 Kyphoscoliotic EDS Kyphoscoliosis
Joint hyperflexibility
Muscle hypotonia
Ocular fragility
Skin hyperextensibility
Atrophic scarring
Arterial rupture
Respiratory compromise in severe cases
PLOD1
FKBP14
Affects folding and cross-linking of collagen
Brittle cornea Syndrome Fragile cornea with risk of rupture
Blue sclerae
Early keratoconus and keratoglobus
Severe myopia
Detachment of retina
Deafness
Mild contractures of fingers
Distal joint hypermobility
ZNF469
PRDM5
Affects intracellular processes
 Spondylodysplastic EDS Hypotonia of muscles
Short stature and bowing of limbs
Skin hyperextensibility
Delayed cognitive and motor development
B4GALT7
B3GALT6
SLC39A13
Affects biosynthesis of glycosaminoglycan and intracellular processes
Musculocontractural EDS Multiple contractures
Club foot
Early craniofacial abnormalities
Skin hyperextensibility
Increased wrinkling of palms
Kidney stones
CHST14
DSE
Affects biosynthesis of glycosaminoglycan
Myopathic EDS Congenital muscle weakness and atrophy, lessening with age
Contractures of proximal joints
Joint hypermobility
Developmental motor delay
COL12A1 Affects myomatrix structure and function
Periodontal EDS Early, severe periodontitis
Detachment of gingiva
Pretibial plaques
Easy bruising
Joint hypermobility
Higher risk of infection
C1R, C1S Affects complement pathways

Collagen and connective tissue:

What is connective tissue: Between the tissues of this body – bone, muscles, organs, nerves – is the connective tissue that holds everything together. Connective tissue is made up of collagen and elastic fibers, cells, and the extracellular matrix.

Tendons and ligaments are made up of more dense connective tissue, with the collagen fibers arranged in parallel for structure. Elastin is also found in the ligaments as well as in the skin.

There are many different connective tissue disorders, including Ehlers-Danlos syndromes, Marfan syndrome, lupus, rheumatoid arthritis, Churg-Strauss syndrome, and more.[ref]

Collagen is the most abundant protein in the body. The connective tissue cells, especially fibroblasts, secrete collagen into the extracellular matrix forming a fibrous network.

Multiple types of collagen: The most common type of collagen is type 1, which is found in skin, tendons, blood vessels, and bones. Cartilage, such as in your nose or ears, is mainly type II collagen. Type III collagen is found supporting soft tissues, while type IV makes up part of the epithelium. Finally, type V collagen is important in cell surfaces, hair, and the placenta. The different types of collagen can also interact with each other in forming different types of connective tissue.

The main amino acids that make up the collagen protein include glycine, proline, and alanine.

Multiple genes encode proteins important in collagen formation. Many of these start with the prefix COL, such as COL5A1. Interacting with the genes are specific enzymes needed in the formation of the connective tissue.

Inside connective tissue cells, a precursor form of collagen, called pro-collagen, is assembled. Then it is secreted into the extracellular space and the final collagen fiber is assembled with the help of enzymes known as collagen peptidases. The COL genes encode the proteins that form the procollagen, which is then acted upon by enzymes to create the different types of collagen in the body.

Focusing on COL5A1 and COL5A2:

Most people diagnosed with classical Ehlers-Danlos syndrome (type III) have a single mutation in the COL5A1 or COL5A2 gene.

The COL5A1 and COL5A2 genes encode proteins important in the formation of Type V collagen. Type I collagen and type V collagen work together in forming collagen in certain areas of the body. Complete lack of type V collagen is lethal in embryo formation.[ref]

In wound healing, type V collagen is important. One way that researchers determined this is through animal studies. Animal models of EDS are created using mice that are bred to lack COL5A1. The lack of COL5A1 causes thin skin along with spontaneous wounds that don’t heal correctly.[ref]

Type V collagen is also important for the joints and spine. Certain mutations in COL5A1 are linked to progressive kyphoscoliosis, which is a curve in the upper back that is both sideways and an arched hump.[ref]

A wide spectrum of symptoms:

A recent study involving 75 people with genetic confirmation of classical EDS illustrated the wide range of symptoms associated with EDS.

The people in the study all had a mutation in the COL5A1 or the COL5A2 gene. In addition to classic symptoms of joint hypermobility and skin hyperextensibility, some patients also had scarring from poor wound healing, delayed motor development, muscle fatigue and cramps, mild scoliosis, blood vessel fragility, rectal prolapse in childhood, and cervical insufficiency during pregnancy. Facial features typical for EDS included epicanthal folds (upper eyelid skin fold), drooping eyelids, prominent eyes, eyes that are closer together than typical, low-set ears, and elongation in the area between nose and mouth.[ref]

The key point here is that not everyone with a classical EDS mutation will have the same features and symptoms. There is a wide range of phenotypes, depending on the specific mutation as well as other genetic variants and environmental factors. Some people will have more severe symptoms, while others will have milder issues.[ref]

Specific types of Ehlers-Danlos Syndrome:

Classical EDS:

Classic EDS, or EDS type I/II, refers to people with joint hypermobility, skin hyperextensibility, easy bruising, tissue fragility, and scarring. In addition to the skin and joint issues, some people with classic EDS will also have vascular complications.

Genetic mutations in classic EDS: As discussed above, people with classic EDS have mutations in the COL5A1 or COL5A2 gene. A list of some of the mutations in these genes is below in the Genetic Variants.

According to research studies, classical EDS is found in about 1 in 20,000 people.[ref]

Vascular Ehlers-Danlos Syndrome:

Considered a rare and severe disorder, vascular Ehlers-Danlos is characterized by fragile, thin skin and blood vessels. The endothelial tissue that lines the blood vessels, intestines, and the uterus is prone to easily rupturing.[ref]

This can result in an aneurysm, intestinal fistula, or bowel ruptures. Usually diagnosed in their 20s or 30s, people with vEDS often have characteristic thin, translucent skin and easy bruising. Diagnosis often follows a major vascular event (e.g. stent, aneurism), abdominal aneurism, or a bowel rupture.[ref][ref]

Genetic mutations in vascular EDS: Diagnosis with vascular Ehlers-Danlos includes a positive genetic test for a pathogenic mutation in the COL3A1 gene. While many rare genetic diseases require two pathogenic mutations for the disease to occur, vascular Ehlers-Danlos can sometimes be caused by carrying just one mutation in the gene.

There are over 500 known mutations in the COL3A1 gene, and the overall frequency of vEDS is 1 in 150,000 people.[ref]

Dermatosparaxis EDS:

Dermatosparaxis EDS, or EDS type VIIC, involves extremely fragile and lax skin. People with this subtype of EDS are often shorter in stature and have a blue discoloration of the whites of their eyes.

Genetic mutations in dermatosparaxis EDS: Rare mutations in the ADAMS2 and ADAMS12 gene are responsible for dermatosparaxis EDS. These genes are involved in cleaving the collagen proteins at the right spot for them to be activated.[ref]

Periodontal Ehlers-Danlos Syndrome:

Another subtype of Ehlers-Danlos involves the gums and teeth. Periodontitis and tooth-root absorption are hallmarks of this subtype.[ref]

Genetic mutations in periodontal EDS: The genetic component of periodontal EDS involves immune systems genes that code for part of the complement system. People with periodontal EDS have a mutation in the C1R (complement 1 receptor) gene. In addition to severe periodontitis, people with periodontal EDS can also have easy bruising and joint hypermobility.[ref]

Hypermobility Ehlers-Dalos Syndrome (hEDS):

Hypermobility Ehlers-Danlos syndrome (hEDS), or EDS type III in the newer definition, is characterized by laxity in the ligaments. This can cause joint dislocation, joint weakness, joint pain, nerve pain, or muscle pain. Additionally, some people can have an increased risk of early-onset arthritis and osteoporosis.[ref]

According to the NIH Rare Disease website: “It is generally considered the least severe form of Ehlers-Danlos syndrome (EDS) although significant complications can occur.“[ref]

No genetic mutation in the diagnosis of hEDS: Hypermobility Ehlers-Danlos is diagnosed based entirely on symptoms. It doesn’t seem to have a genetic cause – at least not one that has been found yet by researchers. Ongoing research may shed light on hEDS sometime soon.

The hypermobility of joints in hEDS generally occurs and is noticeable in the first few years of life. In other words, hEDS isn’t something that develops as an adult, but instead, the hypermobility aspects are apparent from early childhood.[ref]

With hEDS diagnoses, genetic testing is used to rule out other connective tissue disorders including classic EDS mutations, Marfan syndrome, Loeys-Dietz syndrome, osteogenesis imperfecta, and lateral meningocele syndrome.[ref][ref]

Hypermobility Spectrum Disorder (HSD):

Similar to hEDS, hypermobility spectrum disorder (HSD) is a term that is being applied to the group of connective tissue disorders that involve hypermobility in one or more joints, subluxations, and joint dislocations.[ref][ref]

Joint hypermobility syndrome is another term given when diagnosing people with joint hypermobility and no defined molecular or genetic basis.[ref]

Prevalence of diagnosis: In the UK, a recent study found that about 1 in 500 people were diagnosed with either joint hypermobility or Ehlers-Danlos Syndrome. This shows a much greater prevalence than earlier diagnoses of EDS based on genetic testing (1 in 20,000) or even previous prevalence of hEDS (1 in 5,000).[ref]

When you read through the diagnostic criteria for hEDS or hypermobility spectrum disorder, it seems like this is cut-and-dry. Certain symptoms = certain diagnosis. But the reality is that everyone is unique and not everyone fits in a specific box.[ref]

Does having flexible joints mean that you have Ehlers-Danlos?

Up to 25% of kids and teens are considered to have joint hypermobility. Girls are more likely than boys in this tendency, and it is thought to cause no complications in kids.

Thus, simply being a flexible teenage girl does not necessarily mean it is EDS… instead, other symptoms need to also be present such as skin laxity, easy bruising (without other cause), or joint dislocations.[ref]

POTS and hEDS:

POTS stands for postural orthostatic tachycardia syndrome. It is defined as an increase in heart rate of 30 beats/minute (adults) or 40 beats/minute (kids, teens) when going from laying down to standing up.

There is an overlap between people with POTS and hEDS that is not well explained.

Some estimates show that over 40% of people with hEDS also have POTS, but not all research agrees. Part of the difference in studies is that POTS can be defined in different ways, in different clinics. Additionally, much of the data in the studies are self-reported rather than measured in a clinic.[ref]

A recent study at Penn State investigated the link between POTS and hEDS. The study included 91 people with clinically diagnosed POTS. Of those, 31% met the clinical criteria for hEDS. Notably, an additional 24% of participants had some joint hypermobility without meeting the hEDS criteria.[ref]

(Read about genetic variants linked to POTS)

Mast Cell Activation Syndrome and hEDS:

Similar to the overlap with POTS and hEDS, there is an unusually high number of people diagnosed with hEDS along with mast cell activation syndrome (MCAS). Some people have all three diagnoses – POTS, hEDS, and MCAS.

A recent study showed the overlap between MCAS, POTS, and hEDS diagnoses in medical records were 31%.[ref]

Is it totally clear that there is a link between MCAS, POTS, and hEDS?

Well… no. hEDS and MCAS have newly evolving clinical criteria. POTS is often self-diagnosed without a clinical test. There is a lot of murkiness here in the research.

A recent review article in the journal Clinical Reviews of Allergy and Immunology sums it up: “All three clinical entities are controversial in either existence or pathogenesis. MCAS is a poorly defined clinical entity, and many studies do not adhere to the proposed criteria when establishing the diagnosis. Patients previously diagnosed with EDS hypermobility type may not meet the new, stricter criteria for hEDS but may for a less severe hypermobility spectrum disorder (HSD). The pathophysiology of POTS is still unclear. An evidence-based, common pathophysiologic mechanism between any of the two, much less all three conditions, has yet to be described.”[ref]

A biological basis for the connection between MCAS, POTS, and hEDS:

Mast cells are part of the immune system, reacting as part of the body’s first line of defense against invaders. When a mast cell is activated, such as in response to an allergen or viral particle, it will degranulate and release mediators such as histamine, heparin, tryptase, and/or serotonin. Additionally, mast cells can release cytokines such as TNF-alpha or IL-4 in response to specific activators.

Mast cells are also important in wound healing and repair, and mast cells can reside in connective tissue. Mast cells are found abundantly in the skin, gastrointestinal tract, and respiratory tract. Additionally, mast cells can modulate heart rate by releasing histamine or tryptase.[ref]

There are several overlaps between mast cells and hypermobility Ehlers-Danlos syndrome:

  • In the joints, mast cells are an essential part of the pathology of osteoarthritis. Tryptase released from mast cells induces inflammation and causes cartilage breakdown.[ref]
  • In skin scarring, mast cells may also play an important role. Many studies show a higher number of mast cells or mast cell activation in scars.[ref]
  • In tendon injuries, mast cells play an important role in modulating inflammation, pain, and healing. Mast cells are found not only in tendon injuries but also are in the vicinity of peripheral nerves and may be involved in pain communication.[ref]
  • Higher tryptase levels were found in a study of 35 families with skin and connective tissue abnormalities.[ref]

Read more about mast cell activation syndrome and genetics.

Fibromyalgia or ME/CFS and Ehlers-Danlos Syndrome:

Some patients with Ehlers-Danlos syndrome are misdiagnosed as having either fibromyalgia or ME/CFS. In patients without genetic mutations that are diagnosed with hEDS or hypermobility spectrum disorder, fibromyalgia or chronic fatigue may be coexisting conditions.[ref]

A study involving 63 fibromyalgia or ME/CFS diagnosed patients found 81% met the criteria for hypermobility syndrome and 18% met the criteria for hEDS.[ref]

Clinicians reported in the journal Clinical and Experimental Rheumatology that most of their hEDS patients also met the criteria for CFS.[ref]

 


Genetic variants linked to EDS

Member’s: Log in to see your data below. (Also on the Disease Prevention Topic Summary Report)
Not yet a member? Join now.
A couple of notes, before you check your data:

  • 23andMe and AncestryDNA raw data files are not guaranteed to be clinically accurate for medical diagnosis. False positives are possible, and anything you discover here should be replicated with a clinically accurate test.
  • Mistakes are possible in the list below – it’s long, I’m human. Please contact me if you see anything listed incorrectly.
  • This is only a portion of the known EDS mutations. If you or your doctor think that you have Ehlers-Danlos syndrome, you should seek a clinical test that covers all the mutations.

COL5A1 gene – Classical EDS rare mutations:

Check your genetic data for rs863223483 (23andMe v5):

  • G/T: EDS classical[ref]
  • T/T: typical

Members: Your genotype for rs863223483 is .

Check your genetic data for rs863223478 (23andMe v5):

  • C/T: EDS classical[ref]
  • C/C: typical

Members: Your genotype for rs863223478 is .

Check your genetic data for rs863223475 (23andMe v5):

  • D/I: EDS classical[ref]
  • D/D: typical

Members: Your genotype for rs863223475 is .

Check your genetic data for rs863223466 (23andMe v5):

  • A/G: probable EDS classical[ref]
  • G/G: typical

Members: Your genotype for rs863223466 is .

Check your genetic data for rs863223469 (23andMe v5):

  • D/I: EDS classical[ref]
  • D/D: typical

Members: Your genotype for rs863223469 is .

Check your genetic data for rs863223470 (23andMe v5):

  • D/I: EDS classical[ref]
  • D/D: typical

Members: Your genotype for rs863223470 is .

Check your genetic data for rs863223471 (23andMe v5):

  • D/I: EDS classical[ref]
  • D/D: typical

Members: Your genotype for rs863223471 is .

Check your genetic data for rs863223472 (23andMe v5):

  • D/I: EDS classical[ref]
  • I/I: typical

Members: Your genotype for rs863223472 is .

Check your genetic data for rs863223473 (23andMe v5):

  • D/I: EDS classical[ref]
  • D/D: typical

Members: Your genotype for rs863223473 is .

Check your genetic data for rs863223474 (23andMe v5):

  • D/I: EDS classical[ref]
  • I/I: typical

Members: Your genotype for rs863223474 is .

Check your genetic data for rs794727114 (23andMe v5):

  • C/G: EDS classical[ref]
  • G/G: typical

Members: Your genotype for rs794727114 is .

Check your genetic data for rs794727760 (23andMe v5):

  • D/I: EDS classical[ref]
  • I/I: typical

Members: Your genotype for rs794727760 is .

Check your genetic data for rs80338764 (23andMe v5):

  • C/G: EDS classical[ref]
  • G/G: typical

Members: Your genotype for rs80338764 is .

Check your genetic data for rs863223444 (23andMe v5):

  • A/T: EDS classical[ref]
  • T/T: typical

Members: Your genotype for rs863223444 is .

Check your genetic data for rs863223445 (23andMe v5):

  • A/G: EDS classical[ref]
  • G/G: typical

Members: Your genotype for rs863223445 is .

Check your genetic data for rs863223448 (23andMe v5):

  • C/G: EDS classical[ref]
  • G/G: typical

Members: Your genotype for rs863223448 is .

Check your genetic data for rs863223452 (23andMe v5):

  • A/G: EDS classical[ref]
  • G/G: typical

Members: Your genotype for rs863223452 is .

Check your genetic data for rs863223453 (23andMe v5):

  • C/G: EDS classical[ref]
  • G/G: typical

Members: Your genotype for rs863223453 is .

Check your genetic data for rs863223454 (23andMe v5):

  • C/T: EDS classical[ref]
  • C/C: typical

Members: Your genotype for rs863223454 is .

COL5A2 rare mutations:

Check your genetic data for rs863223501 (23andMe v5):

  • C/T: possible EDS classical[ref]
  • C/C: typical

Members: Your genotype for rs863223501 is .

Check your genetic data for rs863223495 (23andMe v5):

  • C/T: possible EDS classical[ref]
  • C/C: typical

Members: Your genotype for rs863223495 is .

Check your genetic data for rs863223491 (23andMe v5):

  • C/T: EDS classical[ref]
  • C/C: typical

Members: Your genotype for rs863223491 is .

More common variants in COL5A1 that affect collagen formation but do NOT cause EDS on their own:

Check your genetic data for rs13946 (23andMe v5; AncestryDNA):

  • C/C: typical
  • C/T: somewhat decreased risk of tendon or ligament injury[ref] reduced relative risk of carpal tunnel syndrome
  • T/T: decreased risk of tendon or ligament injury[ref] reduced relative risk of carpal tunnel syndrome[ref]

Members: Your genotype for rs13946 is .

Check your genetic data for rs61735045 c.1588G>A (p.G530S)(23andMe v4, v5; AncestryDNA):

  • A/A: rare, may cause EDS[ref]
  • A/G: may worsen EDS in conjunction with other COL5A1 mutations[ref]
  • G/G: typical

Members: Your genotype for rs61735045 is .

Vascular EDS mutations:

COL3A1 gene:

Check your genetic data for rs397509369 (23andMe v5):

  • A/G: EDS vascular[ref]
  • G/G: typical

Members: Your genotype for rs397509369 is .

Check your genetic data for rs553203474 (23andMe v5; AncestryDNA):

  • A/G: EDS vascular[ref]
  • G/G: typical

Members: Your genotype for rs553203474 is .

Check your genetic data for rs397509377 (23andMe v5):

  • D/I: EDS vascular[ref]
  • D/D: typical

Members: Your genotype for rs397509377 is .

Check your genetic data for rs587779417 (23andMe v5; AncestryDNA):

  • A/G: EDS vascular[ref]
  • G/G: typical

Members: Your genotype for rs587779417 is .

Check your genetic data for rs587779418 (23andMe v5; AncestryDNA):

  • A/G: EDS vascular[ref]
  • G/G: typical

Members: Your genotype for rs587779418 is .

Check your genetic data for rs587779419 (23andMe v5; AncestryDNA):

  • A/G: EDS vascular[ref]
  • G/G: typical

Members: Your genotype for rs587779419 is .

Check your genetic data for rs587779421 (23andMe v5; AncestryDNA):

  • A/G: EDS vascular[ref]
  • G/G: typical

Members: Your genotype for rs587779421 is .

Check your genetic data for rs587779424 (23andMe v5; AncestryDNA):

  • A/G: EDS vascular[ref]
  • G/G: typical

Members: Your genotype for rs587779424 is .

Check your genetic data for rs587779427 (23andMe v5; AncestryDNA):

  • G/T: EDS vascular[ref]
  • G/G: typical

Members: Your genotype for rs587779427 is .

Check your genetic data for rs587779428 (23andMe v5; AncestryDNA):

  • G/T: EDS vascular[ref]
  • G/G: typical

Members: Your genotype for rs587779428 is .

Check your genetic data for rs587779429 (23andMe v5; AncestryDNA):

  • C/T: EDS vascular[ref]
  • T/T: typical

Members: Your genotype for rs587779429 is .

Check your genetic data for rs587779432 (23andMe v5; AncestryDNA):

  • A/G: EDS vascular[ref]
  • G/G: typical

Members: Your genotype for rs587779432 is .

Check your genetic data for rs587779434 (23andMe v5; AncestryDNA):

  • A/G: EDS vascular[ref]
  • G/G: typical

Members: Your genotype for rs587779434 is .

Classical-like EDS:

TNXB gene mutations:

Check your genetic data for rs368512272 85C>T (23andMe v5):

  • A/G: classic-like EDS possible[ref]
  • G/G: typical

Members: Your genotype for rs368512272 is .

 


Lifehacks for EDS:

Talk with your doctor, of course, before implementing any changes.

Many people with EDS are helped by supporting joints, physical therapy, etc.

Finger orthoses are supports for the finger joints. A small study showed finger orthoses help improve hand function in some people with EDS.[ref]

Vitamin C is a cofactor in collagen synthesis. A severe deficiency of vitamin C causes scurvy, which causes teeth to loosen, gums to deteriorate, and wounds not to heal, all due to a lack of collagen synthesis. Read more on how vitamin C is absorbed, transported, and used by the body.

Zinc is also essential in connective tissue development. Ensure that your diet contains enough zinc.[ref] Learn more about the importance of zinc.

Joint exercise in children: A randomized clinical trial looked at differences between exercising in the full hypermobility range compared to neutral knee extension exercises. Both groups (meaning exercising the knees in general) had a reduction in knee pain. The group that exercised to the full hypermobility range had better (parental reported) self-esteem, psychosocial health, mental health, and behavior.[ref]

Similarly, a clinical trial comparing targeted vs. generalized physical therapy showed that both groups were helped. No additional benefit was seen for targeted physical therapy over generalized therapy.[ref]

Mast cell stabilizers may be helpful for some people with overlapping symptoms of hEDS and mast cell activation syndrome. Mast cell stabilizers include quercetin, vitamin C, D, B6, and B12. Additionally, some doctors recommend H1 and H2 receptor blockers such as cetirizine and cimetidine.[ref][ref] (Read more about Mast Cell Activation Syndrome and mast cell stabilizers)

In the pipeline: Animal research shows promise for new targets of drugs for vascular EDS. Mice with mutations in the COL3A1 gene are used as a model for vEDS, and researchers have found that inhibiting certain molecules may help to prevent aortic rupture. Interestingly, oxytocin was found to decrease risk in pregnancy-associated risks.[ref][ref]

Breath training: A clinical trial of inspiratory muscle strength training investigated whether the breathing exercises would help hEDS patients. The results showed that the inspiratory muscle training improved walking speed, lung function, and exercise capacity.[ref]


Related Articles and Genes:

Histamine Intolerance
Chronic headaches, sinus drainage, itchy hives, problems staying asleep, and heartburn — all of these symptoms can be caused by the body not breaking down histamine very well. Your genetic variants could be causing you to be more sensitive to foods high in histamine. Check your genetic data to see if this could be at the root of your symptoms.

TNF-Alpha: Higher innate levels of this inflammatory cytokine
Do you feel like you are always dealing with inflammation? Joint pain, food sensitivity, etc? Perhaps you are genetically geared towards a higher inflammatory response. Tumor necrosis factor (TNF) is an inflammatory cytokine that acts as a signaling molecule in our immune system.

Rheumatoid Arthritis Genes
Rheumatoid arthritis is caused by an immune system attack on the joints, causing thickening and inflammation of the joint capsule. It is caused by a combination of genetic susceptibility and environmental triggers.



Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University and an undergraduate degree in engineering from Colorado School of Mines. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between the research hidden in scientific journals and everyone's ability to use that information. To contact Debbie, visit the contact page.