Genetics Northern California

Ehlers-Danlos syndrome

General Information
Ehlers-Danlos (EDS) syndrome belongs to a group of disorders known as connective tissue disorders. Connective tissue provides strength and flexibility to different parts of your body. In EDS the connective tissue does not function in the normal way. This difference in the connective tissue can affect the skin, joints, and blood vessels. EDS is quite variable, which means that no two individuals with EDS will have exactly the same features, even if they are in the same family.

Ehlers-Danlos syndrome is thought to affect about 1 in 5,000 people. It affects both males and females of all racial and ethnic backgrounds. It is caused by a genetic change (mutation) in one of several genes that tell the body how to make a protein called collagen. Most forms of EDS are autosomal dominant conditions, meaning that a mutation in just one copy of a collagen gene can cause EDS. Some people with EDS have a parent who also has EDS. In some cases, the parent may be unaware that they have this condition. Other times, there is no one else in the family with EDS. The condition can happen for the first time due to a de novo mutation in one of the collagen genes. The chance for a new mutation rather than an inherited mutation in the family depends on the type of EDS. Any person who has EDS can pass the condition to his/her children. Each child has a 50% chance of inheriting the same condition.

Features of Ehlers-Danlos Syndrome
The three main types of EDS are Classical, Hypermobility, and Vascular. There are also a few other very rare forms of EDS. All types of EDS share some common features but also have features that set them apart.

The common features seen in all forms of EDS include stretchy skin, loose joints, and easy bruising. In addition, the valves in the heart can be “floppy” (mitral valve prolapse). Some people with EDS also experience pain that is not easily explained by their medical findings. EDS does not affect intelligence.

Classical Type- The main features seen in the classical type of EDS include velvety-feeling, stretchy skin, very loose joints and easy bruising. The skin is also more fragile than average and has a tendency for abnormal scarring. The scars may be larger than expected and can sometimes look lumpy. A person with classic EDS may also develop hernias and have mild muscle weakness. 
 
Hypermobility Type- Hypermobility is the medical term for having loose joints and being very flexible. This type of EDS is considered the least severe, but medical problems can and do occur. Joint dislocations and bruising are common with this type of EDS, but the skin may not be as stretchy as other forms of EDS. Over time, the joints become stiff (osteoarthritis) and may break-down (degenerative joint disease). Chronic pain can be present even when there no obvious injury.

Vascular Type- Vascular EDS is a rare form of EDS, affecting about 1 in 250,000 people. Individuals with this type have much stretchier skin and looser joints than other forms of EDS. It also comes with a greater risk for medical problems. Four out of five adults with vascular EDS have a serious medical issue by the time they are 40 years old. The main feature separating this type of EDS from other types is weakness in the blood vessels (vascular system). This means that blood vessels, which carry blood through the body, are more likely to break open suddenly (rupture) or gradually tear (dissection). Due to the fragile blood vessels, this form of EDS has reduced life expectancy. Early diagnosis allows better treatment and may help extend lifespan.


Diagnosing Ehlers-Danlos Syndrome
EDS is usually diagnosed in a genetics clinic by reviewing the family history and performing a specialized physical exam. There are specific criteria that doctors use to decide if a person has EDS and what type it may be.


Genetic Testing
Genetic testing is sometimes used to confirm a diagnosis or help clarify the type of EDS. Testing is not available for all types of EDS. 

Classical: About 50% of people with classical EDS have a mutation that can be found in either the COL5A1 or the COL5A2 gene. These are two genes that code for proteins that make collagen. 

Hypermobility
: This type of EDS does not use genetic testing for diagnosis. The gene (or genes) that cause hypermobility EDS have not been found yet. The only testing available at this time is through research.

Vascular
: 98% of people with this type of EDS have a mutation in COL3A1.

A negative genetic test (no mutation found) does not change the diagnosis, but it means that our current technology is not able to find the specific mutation in that person or family. If the specific mutation of someone with EDS is known, prenatal diagnostic testing is available during pregnancy.

Treatment of Ehlers-Danlos Syndrome
The best treatment for someone with EDS is specialized care for symptoms related to the condition. Physical therapy and the use of braces can sometimes be helpful with loose joints and pain. Pain management is often an important part of treatment for EDS. Any heart problems, particularly in people with vascular EDS should be followed closely by a cardiologist. In certain situations, medication is used to help decrease the chance of a serious medical problem happening.

Lifestyle modifications can also help. People with EDS are encouraged to participate in non-weight-bearing exercise, such as swimming. This helps to strengthen muscles and joints, and reduces the chance of dislocations.

Support Resources
Ehlers-Danlos National Foundation
http://www.ednf.org/

References
Gene Reviews on Ehlers-Danlos Syndrome:
Classic: http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=eds
Hypermobility Type: http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=eds3
Vascular Type: http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=eds4

NIH: Genetics Home Reference on Ehlers-Danlos syndrome:
http://ghr.nlm.nih.gov/condition/ehlers-danlos-syndrome

Written by:     Elizabeth Stark, MS
Reviewed by:  Kim Barr, MS CGC
                     Emily Chen, MD
                     SFO Genetics

Last edited:       July 16, 2010
Last reviewed:  September 1, 2010