Ehlers-Danlos syndromes

Información en español Title

Other Names:

ED syndrome; EDS; Ehlers Danlos syndrome

Categories:

Connective tissue diseases

Subtypes:

Summary Summary

Ehlers-Danlos syndromes (EDS) are a group of inherited connective tissue disorders caused by abnormalities in the structure, production, and/or processing of collagen. The new classification, from 2017, includes 13 subtypes of EDS. Although other forms of the condition may 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. 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]

Please visit the following link from the Ehlers-Danlos Society to learn more about the new classification and the different subtypes: https://ehlers-danlos.com/eds-types/

Last updated: 4/20/2017

Symptoms Symptoms

There are 13 types of Ehlers-Danlos syndromes (EDS), with a significant overlap in features:^[1]^[2]^[4]

Hypermobile EDS - characterized primarily by joint hypermobility affecting both large and small joints, which may lead to recurrent joint dislocations and subluxations (partial dislocation). In general, people with this type have soft, smooth and velvety skin with easy bruising and chronic pain of the muscles and/or bones.
Classical EDS - 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 also frequently seen. Hypotonia and delayed motor development may occur.
Vascular EDS - 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. People with this type 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); recession of the gums; and a decreased amount of fat under the skin.
Kyphoscoliosis EDS - 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 corneas; 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 EDS - 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 EDS - associated with extremely fragile skin leading to severe bruising and scarring; saggy, redundant skin, especially on the face; and hernias.
Brittle Cornea Syndrome (BCS) characterized by thin cornea, early onset progressive keratoglobus; and blue sclerae.
Classical-like EDS (clEDS) characterized by skin hyperextensibility with velvety skin texture and absence of atrophic scarring, generalized joint hypermobility (GJH) with or without recurrent dislocations (most often shoulder and ankle), and easily bruised skin or spontaneous ecchymoses (discolorations of the skin resulting from bleeding underneath).
Spondylodysplastic EDS (spEDS) characterized by short stature (progressive in childhood), muscle hypotonia (ranging from severe congenital, to mild later-onset), and bowing of limbs.
Musculocontractural EDS (mcEDS) characterized by congenital multiple contractures, characteristically adduction-flexion contractures and/or talipes equinovarus (clubfoot), characteristic craniofacial features, which are evident at birth or in early infancy, and skin features such as skin hyperextensibility, easy bruisability, skin fragility with atrophic scars, increased palmar wrinkling.
Myopathic EDS (mEDS) characterized by congenital muscle hypotonia, and/or muscle atrophy, that improves with age, Proximal joint contractures (joints of the knee, hip and elbow); and hypermobility of distal joints (joints of the ankles, wrists, feet and hands).
Periodontal EDS (pEDS) characterized by severe and intractable periodontitis of early onset (childhood or adolescence), lack of attached gingiva, pretibial plaques; and family history of a first-degree relative who meets clinical criteria.
Cardiac-valvular EDS (cvEDS) characterized by severe progressive cardiac-valvular problems (aortic valve, mitral valve), skin problems (hyperextensibility, atrophic scars, thin skin, easy bruising) and joint hypermobility (generalized or restricted to small joints).

You can view more detailed information about all 13 types of EDS on the Ehlers-Danlos Society's website. Other forms of the condition may exist but are extremely rare and are not well-characterized.

Last updated: 4/20/2017

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Cause Cause

Ehlers-Danlos syndromes (EDS) are genetic disorders that can be caused by mutations in several different genes, including COL5A1, COL5A2, COL1A1, COL3A1, TNXB, PLOD1, COL1A2, FKBP14 and ADAMTS2. However, the underlying genetic cause is unknown in some families.^[1]^[5]

Mutations in these genes usually change 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 signs and symptoms of EDS.^[6]

The Ehlers-Danlos Society website has a more complete list of genes associated with EDS.

Last updated: 4/20/2017

Inheritance Inheritance

The inheritance pattern of Ehlers-Danlos syndromes (EDS) varies by subtype. The arthrochalasia EDS, classical EDS, hypermobile EDS, periodontal EDS, some cases of myopatic EDS, and vascular forms of EDS usually have an autosomal dominant pattern of inheritance.^[1]^[2] This means that to be affected, a person needs to have a change (mutation) in only one copy of the disease-causing gene in each cell. In some cases, a person with these forms of EDS 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 family history of EDS. Each child of a person with autosomal dominant EDS has a 50% chance of inheriting the mutation.

The dermatosparaxis EDS, kyphoscoliosis EDS, classical-like EDS, cardiac-vascular EDS, brittle cornea syndrome, spondylodysplastic EDS, musculocontractural EDS, and some cases of myopatic EDS are inherited in an autosomal recessive pattern.^[1]^[2] This means that have any of these types of EDS, a person must have a mutation in both copies of the disease-causing 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: 4/20/2017

Diagnosis Diagnosis

A diagnosis of the Ehlers-Danlos syndromes (EDS) 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. People with EDS often have abnormalities of certain types of collagen.
Genetic testing is available for many subtypes of EDS; 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 the kyphoscoliosis type.

Last updated: 3/27/2017

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

The treatment and management of Ehlers-Danlos syndrome (EDS) is focused on preventing serious complications and relieving signs and symptoms.^[7] The features of EDS vary by subtype, so management strategies differ slightly.^[7] Because several body systems may be affected, different medical specialists may need to be involved.^[8] The main aspects of management include cardiovascular (heart) work-up, physical therapy, pain management, and psychological follow-up as needed.^[8] Surgery is sometimes recommended for various reasons in people with EDS. However, depending on the type of EDS and severity, there may be an increased risk of various surgical complications such as wound healing problems, excessive bleeding, dissection, and hernias.^[9]^[10] Surgery for non-life threatening conditions particularly should be carefully considered.^[10]

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: 9/17/2018

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 syndromes (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.^[1]^[7]

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.^[1]^[7]

Last updated: 4/10/2017

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

The Ehlers-Danlos Society has a EDS Medical Professionals Directory and an EDS Center for Research & Clinical Care.
To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

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 related to Ehlers-Danlos syndromes. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.
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

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s 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

EDS Awareness
PO Box 229
Mason, OH 45040
E-mail: https://www.chronicpainpartners.com/contact-us/
Website: https://www.chronicpainpartners.com/about-us/
Ehlers-Danlos Society
PO Box 87463
Montgomery Village, MD 20886
Telephone: 410-670-7577
E-mail: info@ehlers-danlos.com , https://www.ehlers-danlos.com/eds-helpline/
Website: https://www.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: https://www.ehlers-danlos.org/
Hypermobility Syndromes Association (HMSA)
49 Greek Street
London, WD1 4EG United Kingdom
Telephone: 033 3011 6388
E-mail: http://hypermobility.org/contact-us/
Website: http://hypermobility.org/
The Ehlers-Danlos Society – Europe Office
Office 7
35-37 Ludgate Hill
London, EC4M 7JN United Kingdom
Telephone: +44 203 887 6132
E-mail: info@ehlers-danlos.com , https://www.ehlers-danlos.com/eds-helpline/
Website: https://www.ehlers-danlos.com/
The Zebra Network
1122 Kenilworth Drive
Suite 307
Towson, MD 21204
Telephone: 410-825-0995
E-mail: victoria@thezebranetwork.org
Website: http://thezebranetwork.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).

Do you know of an organization? We want to hear from you.

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.

Community Resources

The Job Accommodation Network (JAN) has information on workplace accommodations and disability employment issues related to this condition. JAN is a service of the Office of Disability Employment Policy in the U.S. Department of Labor.

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 syndromes. This website is maintained by the National Library of Medicine.
The Mayo Clinic Web site provides further information on Ehlers-Danlos syndromes.
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 syndromes.
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 syndromes. Click on the link to view a sample search on this topic.

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.

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.
Malfait F, Francomano C, Byers P et al. The 2017 international classification of the Ehlers–Danlos syndromes. Am J Med Genet C Semin Med Genet. March, 2017; 175(1):8-26. http://onlinelibrary.wiley.com/doi/10.1002/ajmg.c.31552/full.
EDS Types. The Ehlers-Danlos Society. March 16, 2017; http://ehlers-danlos.com/eds-types/.
Ehlers-Danlos syndrome. Genetics Home Reference. November, 2015; http://ghr.nlm.nih.gov/condition=ehlersdanlossyndrome.
Pauker SP & Stoler J. Overview of the management of Ehlers-Danlos syndromes. UpToDate. 2016; http://www.uptodate.com/contents/overview-of-the-management-of-ehlers-danlos-syndromes.
Malfait F, De Paepe A. The Ehlers-Danlos syndrome. Adv Exp Med Biol. 2014; 802:129-143. https://www.ncbi.nlm.nih.gov/pubmed/24443025.
Ehlers-Danlos syndrome. Mayo Clinic. October 13, 2017; https://www.mayoclinic.org/diseases-conditions/ehlers-danlos-syndrome/diagnosis-treatment/drc-20362149.
Ehlers Danlos Syndromes. National Organization for Rare Disorders (NORD). 2017; https://rarediseases.org/rare-diseases/ehlers-danlos-syndrome/.