Genetics Northern California

Ehlers-Danlos syndrome

General Information
Types of Ehlers-Danlos Syndrome (EDS)
Diagnosing Hypermobile EDS
Genetic Testing
Family History of EDS
Joint Hypermobility in Children
Treatment of Hypermobile EDS 
Support Resources

General Information
Joint hypermobility (loose joints) is a common condition that can lead to repeat joint dislocations, partial dislocations, and chronic pain.  About 1 in 30 adults has joint hypermobility and it is more common in younger adults and in women. Flexible joints are normal in children. Some people with joint hypermobility have mild differences in other body parts, such as soft stretchy skin, a history of hernias, stretch marks in unusual places, and slightly larger scars than usual. There may also be family members with similar symptoms.

For most people, joint hypermobility is a trait, like height. Just as there is no “height gene,” there is no “joint mobility gene”. The amount of flexibility in your joints is determined by the genes you inherit and your environment, like your weight, exercise, and past injuries. 

Rarely, joint hypermobility can be part of a genetic syndrome. These genetic syndromes are known as the Ehlers-Danlos syndromes. 

Types of Ehlers-Danlos Syndrome
Ehlers-Danlos syndrome (EDS) is not a single condition. There are many different types of EDS. Some features are common, like joint hypermobility, skin differences, and easy bruising. But each EDS type has unique features and different genetic causes. A person with one type of EDS will not suddenly change to have a different type. 

Examples of EDS types and their key features include:

Classical - The main features seen in classical EDS include very abnormally stretchy skin, with very abnormal scarring, where even small scrapes turn into large, spread-out scars. Joint hypermobility is common in this type of EDS. Major health problems, such as problems with the heart or blood vessels, are not common.
Vascular - Vascular EDS is a very rare type of EDS. It also comes with the greatest risk of medical problems. Four out of five adults with vascular EDS have a serious medical issue before the age of 40. One unique feature in this type of EDS is weak arteries (blood vessels that carry blood from the heart to the body). These blood vessels are more likely to break open suddenly (rupture) or gradually tear (dissection). Another unique feature is organs that rupture more easily. The intestines and uterus are the two organs most likely to rupture in this condition. Weak veins may cause easy bruising and varicose veins, but this happens in many people and is not unique to EDS. Early diagnosis allows better treatment and may help extend lifespan.

Rare Pediatric Types - There are several different types of EDS that affect children. Unique features in these conditions may include skin that tears open easily, hip dislocations at birth, clubfeet, or severe curving of the spine. These types of EDS are usually noticed in infants and children due to differences in the bones, heart, skin, or other organs. The pediatric types of EDS are not suspected in adults with joint hypermobility.

Hypermobile - Individuals with joint hypermobility but without the unique features of other types of EDS are sometimes given a diagnosis of hypermobile EDS. This is by far the most common type of EDS. 

Hypermobile EDS is very different from other types of EDS in the following ways:
•  There is no known genetic cause for hypermobile EDS.
•  Unlike other types of EDS, hypermobile EDS is not thought to be caused by a single gene. 
•  Research shows that testing the genes that cause other types of EDS does NOT help to diagnose people with symptoms of hypermobile EDS
•  People with hypermobile EDS are not at higher risk for the serious health concerns found in other types of EDS, although chronic pain is common.

For reasons that are not understood, some people with hypermobile EDS can have: 
•  Chronic fatigue
•  Strong allergic reactions (hives, swelling) 
•  An increase in the heart rate when standing up 
•  Easy bruising
•  Gastrointestinal symptoms (abdominal pain, constipation, diarrhea)
•  Chronic pain
These symptoms are not used to diagnose hypermobile EDS. There are also no special treatments recommended for a person with hypermobile EDS who has any of these symptoms.  

Diagnosing Hypermobile EDS
There are specific criteria used to diagnose hypermobile EDS. Any doctor can perform an exam and compare your symptoms to the criteria checklist. A genetics appointment is not needed to make a diagnosis. The checklist can be found online: 
A person with joint hypermobility who does not meet the criteria for hypermobile EDS may be given a diagnosis of “Joint Hypermobility Syndrome”. It is important to know that a diagnosis of hypermobile EDS or joint hypermobility syndrome does not change a person’s medical care or treatment plan. 

Genetic Testing 
Genetic testing is sometimes used to help diagnosis a type of EDS for which the genetic cause is known. For example, a person who has skin and joint findings, plus a family history of sudden blood vessel rupture at a young age, might be tested for vascular EDS.

In general, genetic testing is done when a person has joint hypermobility, skin differences, and at least one of the following unique features: 
•  Personal or family history of blood vessel weakness (aneurysm/rupture/dissection) or  sudden unexplained death of a close relative under 40
•  Unusual eye problems, such as lens dislocation, retinal detachment, or globe rupture
•  Sudden collapse of a lung
•  Cleft palate or bifid uvula (differences in how the mouth and throat formed)
•  Very abnormal skin stretchiness or very abnormal scarring

Adults without any of these symptoms or medical history are unlikely to have a type of EDS that has a genetic test or a special treatment. 
Classical: Most people with classical EDS have a difference in either the COL5A1 or the COL5A2 gene. These are two genes that code for proteins that make collagen. 
Vascular: Almost all people with vascular EDS have a difference in the COL3A1 gene.
Hypermobile: This type of EDS does not use genetic testing for diagnosis. Testing for other types of EDS is not recommended.

Family History of EDS
When there is a family history of EDS, it is important to know the specific type of EDS. This can help guide testing and treatment options. In a family with vascular or classic EDS, for example, a review of genetic test results in a family member can help determine if others in the family could have EDS. For those with a family history of hypermobile EDS, no genetic test can confirm if another family member is affected. An exam (ideally after childhood) can look for features of hypermobile EDS. The child of a person with hypermobile EDS may naturally have looser joints, since children often share traits with parents. However, it is hard to predict whether that child will develop the same symptoms as their parent.

Joint Hypermobility in Children
Joints are naturally looser in children and the diagnostic criteria used to evaluate joint hypermobility cannot be used in children under 7 years old. For a child with loose joints, more testing might be done only if there are motor delays (such as late walking), delays in development (such as late talking), or birth defects of the bones, body, or face. 

Treatment of Hypermobile EDS 
There is no specific treatment for someone with a diagnosis of hypermobile EDS. Symptoms are usually dealt with as they happen. Start by talking with your primary doctor. A treatment plan may include physical therapy, orthopedic (bone/joint) care, chronic pain clinic, and cardiology follow-up, depending on the symptoms. 

Preventive care focuses on staying healthy. 
•  Practice stability-based strengthening exercises [It may take months or years for significant progress to be noticed]. A physical therapist can be helpful as a guide
•  Exercise regularly with low impact exercises: swimming, walking, biking
•  Avoid or limit: high impact sports, high resistance/isometric exercise, heavy lifting, joint hyperextension (i.e., yoga), over-doing exercise 
•  Follow good sleep hygiene
•  Stay hydrated to decrease blood pressure symptoms. 
•  KP Resource: Hypermobility

Support Resources
The Ehlers-Danlos Society

Ehlers-Danlos National Foundation

GeneReviews on Ehlers-Danlos Syndromes:
Classical EDS:
Vascular EDS: 
Hypermobile EDS:

Last reviewed: June 17, 2020
Reviewed by: Bryce Mendelsohn, MD, PhD
        Kimberly Barr, MS, LCGC