Ehlers-Danlos syndrome

Información en español Title

Other Names:

ED syndrome; EDS; Ehlers Danlos syndrome

Categories:

Connective tissue diseases

Summary Summary

Ehlers-Danlos syndrome (EDS) is a group of inherited connective tissue disorders that is caused by abnormalities in the structure, production, and/or processing of collagen. There are 6 major forms of EDS: hypermobility type, classic type, vascular type, kyphoscoliosis type, arthrochalasia type, and dermatosparaxis type. Although other forms of the condition exist, they are extremely rare and are not well-characterized. The signs and symptoms of EDS vary by type and range from mildly loose joints to life-threatening complications. Features shared by many types include joint hypermobility and soft, velvety skin that is highly elastic (stretchy) and bruises easily. Changes (mutations) in a variety of genes may lead to EDS; however, the underlying genetic cause in some families is unknown. Depending on the subtype, EDS may be inherited in an autosomal dominant or an autosomal recessive manner. There is no specific cure for EDS. The treatment and management is focused on preventing serious complications and relieving associated signs and symptoms.^[1]^[2]^[3]

Last updated: 3/20/2016

Symptoms Symptoms

There are six major types of Ehlers-Danlos syndrome (EDS). Although there is significant overlap in associated features, the subtypes are classified based on their unique signs and symptoms:^[1]^[2]

Hypermobility type - characterized primarily by joint hypermobility affecting both large (elbows, knees) and small (fingers, toes) joints which may lead to recurrent joint dislocations and subluxations (partial dislocation). Affected people generally experience skin involvement (soft, smooth and velvety skin with easy bruising) and chronic pain of the muscles and/or bones, as well.

Classic type - associated with extremely elastic (stretchy), smooth skin that is fragile and bruises easily; wide, atrophic scars (flat or depressed scars); and joint hypermobility. Molluscoid pseudotumors (calcified hematomas over pressure points such as the elbow) and spheroids (fat-containing cysts on forearms and shins) are frequently diagnosed in affected people. Hypotonia and delayed motor development may occur, as well.

Vascular type - characterized by thin, translucent skin that is extremely fragile and bruises easily. Arteries and certain organs such as the intestines and uterus are also fragile and prone to rupture. Affected people typically have short stature; thin scalp hair; and characteristic facial features including large eyes, a thin nose and lobeless ears. Joint hypermobility is present, but generally confined to the small joints (fingers, toes). Other common features include club foot; tendon and/or muscle rupture; acrogeria (premature aging of the skin of the hands and feet); early onset varicose veins; pneumothorax (collapse of a lung); gingival (gums) recession; and a decreased amount of subcutaneous (under the skin) fat.

Kyphoscoliosis type - associated with severe hypotonia at birth, delayed motor development, progressive scoliosis (present from birth), and scleral fragility. Affected people may also have easy bruising; fragile arteries that are prone to rupture; unusually small cornia; and osteopenia (low bone density). Other common features include a "marfanoid habitus" which is characterized by long, slender fingers (arachnodactyly); unusually long limbs; and a sunken chest (pectus excavatum) or protruding chest (pectus carinatum).

Arthrochalasia type - characterized by severe joint hypermobility and congenital hip dislocation. Other common features include fragile, elastic skin with easy bruising; hypotonia; kyphoscoliosis (kyphosis and scoliosis); and mild osteopenia.

Dermatosparaxis type - associated with extremely fragile skin leading to severe bruising and scarring; saggy, redundant skin, especially on the face; and hernias.

For more information on each subtype, please click on the links above. You can also find more detailed information on Medscape Reference's Web site or the Ehlers-Danlos National Foundation's Web site.

Although other forms of the condition exist, they are extremely rare and are not well-characterized.

Last updated: 5/21/2015

Cause Cause

Ehlers-Danlos syndrome can be caused by changes (mutations) in several different genes (COL5A1, COL5A2, COL1A1, COL3A1, TNXB, PLOD1, COL1A2, and ADAMTS2). However, the underlying genetic cause is unknown in some families.^[1]

Mutations in these genes usually alter the structure, production, and/or processing of collagen or proteins that interact with collagen. Collagen provides structure and strength to connective tissues throughout the body. A defect in collagen can weaken connective tissues in the skin, bones, blood vessels, and organs resulting in the features of the disorder.^[4]

Last updated: 5/21/2015

Inheritance Inheritance

The inheritance pattern of Ehlers-Danlos syndrome (EDS) varies by subtype. The arthrochalasia, classic, hypermobility, and vascular forms of the disorder usually have an autosomal dominant pattern of inheritance.^[1]^[2] This means that to be affected, a person only needs a change (mutation) in one copy of the responsible gene in each cell. In some cases, an affected person inherits the mutation from an affected parent. Other cases may result from new (de novo) mutations in the gene. These cases occur in people with no history of the disorder in their family. A person with one of these subtypes has a 50% chance with each pregnancy of passing along the altered gene to his or her child.

The dermatosparaxis and kyphoscoliosis types of EDS are inherited in an autosomal recessive pattern.^[1]^[2] This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell. The parents of an affected person usually each carry one mutated copy of the gene and are referred to as carriers. Carriers typically do not show signs or symptoms of the condition. When two carriers of an autosomal recessive condition have children, each child has a 25% (1 in 4) risk to have the condition, a 50% (1 in 2) risk to be a carrier like each of the parents, and a 25% chance to not have the condition and not be a carrier.

Last updated: 5/21/2015

Diagnosis Diagnosis

A diagnosis of Ehlers-Danlos syndrome is typically based on the presence of characteristic signs and symptoms. Depending on the subtype suspected, some of the following tests may be ordered to support the diagnosis:^[1]^[2]^[3]

Collagen typing performed on a skin biopsy may aid in the diagnosis of vascular type, arthrochalasia type, and dermatosparaxis type. Collagen is a tough, fiber-like protein that makes up about a third of body protein. It is part of the structure of tendons, bones, and connective tissues. People with Ehlers-Danlos syndrome often have abnormalities of certain types of collagen.
Genetic testing is available for many subtypes of Ehlers-Danlos syndrome; however, it is not an option for most families with the hypermobility type.
Imaging studies such as CT scan, MRI, ultrasound, and angiography may be useful in identifying certain features of the condition.
Urine tests to detect deficiencies in certain enzymes that are important for collagen formation may be helpful in diagnosing kyphoscoliosis type.

Last updated: 5/21/2015

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
Orphanet lists international laboratories offering diagnostic testing for this condition.

Treatment Treatment

There is no specific cure for Ehlers-Danlos syndrome (EDS). The treatment and management is focused on preventing serious complications and relieving associated signs and symptoms. Because the features of EDS vary by subtype, management strategies differ slightly.^[5]

For more specific information on the treatment of each subtype, please click on the links below:

Please speak to your healthcare provider if you have any questions about your personal medical management plan.

Last updated: 5/22/2015

Management Guidelines

Project OrphanAnesthesia is a project whose aim is to create peer-reviewed, readily accessible guidelines for patients with rare diseases and for the anesthesiologists caring for them. The project is a collaborative effort of the German Society of Anesthesiology and Intensive Care, Orphanet, the European Society of Pediatric Anesthesia, anesthetists and rare disease experts with the aim to contribute to patient safety.

Prognosis Prognosis

The long-term outlook (prognosis) for people with Ehlers-Danlos syndrome (EDS) varies by subtype. The vascular type is typically the most severe form of EDS and is often associated with a shortened lifespan. People affected by vascular EDS have a median life expectancy of 48 years and many will have a major event by age 40. The lifespan of people with the kyphoscoliosis form is also decreased, largely due to the vascular involvement and the potential for restrictive lung disease.^[5]^[1]

Other forms of EDS are typically not as dangerous and can be associated with normal lifespans. Affected people can often live healthy if somewhat restricted lives.^[5]^[1]

Last updated: 5/22/2015

Do you have updated information on this condition? Let us know.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are studying or have studied Ehlers-Danlos syndrome. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.
Ehlers Danlos National Foundation has a list of current research projects for Ehlers-Danlos syndrome.
The Research Portfolio Online Reporting Tool (RePORT) provides access to reports, data, and analyses of research activities at the National Institutes of Health (NIH), including information on NIH expenditures and the results of NIH-supported research. Although these projects may not conduct studies on humans, you may want to contact the investigators to learn more. To search for studies, enter the disease name in the "Text Search" box. Then click "Submit Query".

Organizations Organizations

Nonprofit support and advocacy groups bring together patients, families, medical professionals, and researchers. These groups often raise awareness, provide support, and develop patient-centered information. Many are the driving force behind research for better treatments and possible cures. They can direct people to research, resources, and services. Many groups also have experts who serve as medical advisors. Visit their website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Ehlers-Danlos Society
(formerly Ehlers Danlos National Foundation)
7918 Jones Branch Drive
Suite 300
McLean, VA 22102
Telephone: 703-506-2892
Fax: 703-506-3266
E-mail: info@ehlers-danlos.com
Website: http://ehlers-danlos.com/
Ehlers-Danlos Support UK
PO Box 748
Borehamwood WD6 9HU
United Kingdom
Toll-free: 0800 907 8518 (in the UK)
Telephone: 0208 736 5604
E-mail: director@ehlers-danlos.org
Website: http://www.ehlers-danlos.org

Social Networking Websites

RareConnect has an online community for patients and families with this condition so they can connect with others and share their experiences living with a rare disease. The project is a joint collaboration between EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders).

Organizations Providing General Support

Coalition for Heritable Disorders of Connective Tissue
4301 Connecticut Avenue, Suite 404
Washington, DC 20008-2304
Telephone: 202-362-9599
Fax: 202-966-8553
E-mail: chdct@pxe.org
Website: http://www.chdct2.org/index.htm

Do you know of an organization? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Education Resources

The Genetics Education Materials for School Success (GEMSS) aims to assure that all children with genetic health conditions succeed in school-life. Their Web site offers general and condition-specific education resources to help teachers and parents better understand the needs of students who have genetic conditions.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Genetics Home Reference (GHR) contains information on Ehlers-Danlos syndrome. This website is maintained by the National Library of Medicine.
The Mayo Clinic Web site provides further information on Ehlers-Danlos syndrome.
MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
The Merck Manual provides information on this condition for patients and caregivers.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
Ehlers-Danlos Syndrome
Genetics of Ehlers-Danlos Syndrome
The Merck Manual for health care professionals provides information on Ehlers-Danlos syndrome.
MeSH® (Medical Subject Headings) is a terminology tool used by the National Library of Medicine. Click on the link to view information on this topic.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
PubMed is a searchable database of medical literature and lists journal articles that discuss Ehlers-Danlos syndrome. Click on the link to view a sample search on this topic.

News & Events News & Events

NCATS Co-Sponsored Conferences

2015 Collagen Gordon Research Conference and Gordon Research Seminar Sunday, July 12, 2015 - Friday, July 17, 2015
Location: New London, NH
Description: The 2015 Collagen GRC program will include invited and platform presentations as well as posters on (a) new data and concepts about the genetics, chemistry, biology and pathology of collagens; (b) advances in closely related areas of research, such as cell-matrix interactions, developmental biology and diseases of connective tissues, and bioengineering, that are relevant to the collagen field; (c) new and emerging technologies and approaches that may be applied to the collagen field.

Contact: Hung Tseng, Ph.D., (301) 496-0810, tsengh@mail.nih.gov

Co-funding Institute(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases, Office of Rare Diseases Research

Related Diseases Related Diseases

The following diseases are related to Ehlers-Danlos syndrome. If you have a question about any of these diseases, you can contact GARD.

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

I have a friend who has TRAPS, as well as Ehlers-Danlos syndrome. Can TRAPS cause very low immunity throughout a person's life? Can Ehlers-Danlos syndrome be associated with immune system dysfunction? Can having both conditions cause low immunity? See answer
Are there different types of Ehlers-Danlos syndrome? See answer
Can you have children if you have Ehlers-Danlos syndrome? See answer
What causes Ehlers-Danlos syndrome and what are the symptoms? See answer

Have a question? Contact a GARD Information Specialist.

References References

Defendi GL. Genetics of Ehlers-Danlos Syndrome. Medscape Reference. August, 2015; http://emedicine.medscape.com/article/943567-overview.
Pauker SP & Stoler J. Clinical manifestations and diagnosis of Ehlers-Danlos syndromes. UpToDate. February 22, 2016; http://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-ehlers-danlos-syndromes.
Sobey G. Ehlers-Danlos syndrome: how to diagnose and when to perform genetic tests. Arch Dis Child. Jan 2015; 100(1):57-61. https://www.ncbi.nlm.nih.gov/pubmed/24994860.
Ehlers-Danlos syndrome. Genetics Home Reference. November, 2015; http://ghr.nlm.nih.gov/condition=ehlersdanlossyndrome.
Susan P Pauker, MD, FACMG; Joan Stoler, MD. Overview of the management of Ehlers-Danlos syndromes. UpToDate. March 2014; Accessed 5/22/2015.