Classical Ehlers-Danlos syndrome

Información en español Title

Other Names:

Classic Ehlers-Danlos syndrome; Ehlers-Danlos syndrome type 1 (formerly); Ehlers-Danlos syndrome type 2 (formerly); Classic Ehlers-Danlos syndrome; Ehlers-Danlos syndrome type 1 (formerly); Ehlers-Danlos syndrome type 2 (formerly); Ehlers-Danlos syndrome, classic type See More

Categories:

Connective tissue diseases

Summary Summary

Classical Ehlers-Danlos syndrome (EDS) is a genetic connective tissue disorder that is caused by defects in a protein called collagen. Common symptoms include skin hyperextensibility, abnormal wound healing, and joint hypermobility.^[1]^[2] More than 90% of people with classical EDS have mutations in COL5A1 or COL5A2, two genes which encode type V collagen. In rare cases, mutations in the gene encoding type I collagen, COL1A1 gene, may be found.^[3] The condition is inherited in an autosomal dominant manner.^[2] Treatment and management is focused on preventing serious complications and relieving associated symptoms.^[2]^[4]

Last updated: 6/30/2017

Symptoms Symptoms

The signs and symptoms of classical EDS vary but may include:^[2]^[1]

Smooth, velvety skin that is highly elastic (stretchy) and bruises easily
Abnormal wound healing that may result in wide, atrophic scars (flat and/or depressed scars)
Joint hypermobility that leads to frequent dislocations and subluxations (partial dislocations)
Molluscoid pseudotumors (calcified hematomas over pressure points such as the elbow)
Subcutaneous spheroids (fat-containing cysts that are often found on the forearms and/or shins)
Hypotonia
Delayed motor development
Tissue fragility that may lead to hernias, rectal prolapse, and other complications
Cardiovascular abnormalities such as mitral valve prolapse or aortic root dilatation (enlargement of the blood vessel that distributes blood from the heart to the rest of the body)
Pregnancy may be complicated by premature rupture of membranes

Last updated: 4/21/2017

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Abnormal nasal morphology	Very frequent (present in 80%-99% of cases)
Abnormality of the gingiva	Very frequent (present in 80%-99% of cases)
Abnormality of the tongue	Very frequent (present in 80%-99% of cases)
Arachnodactyly	Very frequent (present in 80%-99% of cases)
Arterial dissection	Very frequent (present in 80%-99% of cases)
Asthma	Very frequent (present in 80%-99% of cases)
Atypical scarring of skin	Very frequent (present in 80%-99% of cases)
Eczema	Very frequent (present in 80%-99% of cases)
Emphysema	Very frequent (present in 80%-99% of cases)
Glaucoma	Very frequent (present in 80%-99% of cases)
High, narrow palate	Very frequent (present in 80%-99% of cases)
Hyperextensible skin	Very frequent (present in 80%-99% of cases)
Hyperlordosis	Very frequent (present in 80%-99% of cases)
Hypertension	Very frequent (present in 80%-99% of cases)
Hypotension	Very frequent (present in 80%-99% of cases)
Joint hyperflexibility	Very frequent (present in 80%-99% of cases)
Malar prominence	Very frequent (present in 80%-99% of cases)
Pectus carinatum	Very frequent (present in 80%-99% of cases)
Petechiae	Very frequent (present in 80%-99% of cases)
Shagreen patch	Very frequent (present in 80%-99% of cases)
Spina bifida occulta	Very frequent (present in 80%-99% of cases)
Striae distensae	Very frequent (present in 80%-99% of cases)
Triangular face	Very frequent (present in 80%-99% of cases)
Acrocyanosis	Frequent (present in 30%-79% of cases)
Aplasia/Hypoplasia of the abdominal wall musculature	Frequent (present in 30%-79% of cases)
Bruising susceptibility	Frequent (present in 30%-79% of cases)
Erythema	Frequent (present in 30%-79% of cases)
Hiatus hernia	Frequent (present in 30%-79% of cases)
Hypoplasia of the ear cartilage	Frequent (present in 30%-79% of cases)
Joint dislocation	Frequent (present in 30%-79% of cases)
Mitral valve prolapse	Frequent (present in 30%-79% of cases)
Myalgia	Frequent (present in 30%-79% of cases)
Narrow face	Frequent (present in 30%-79% of cases)
Premature birth	Frequent (present in 30%-79% of cases)
Scoliosis	Frequent (present in 30%-79% of cases)
Thin skin	Frequent (present in 30%-79% of cases)
Tricuspid valve prolapse	Frequent (present in 30%-79% of cases)
Umbilical hernia	Frequent (present in 30%-79% of cases)
Venous insufficiency	Frequent (present in 30%-79% of cases)
Abnormality of the renal tubule	Occasional (present in 5%-29% of cases)
Atrial septal defect	Occasional (present in 5%-29% of cases)
Blue sclerae	Occasional (present in 5%-29% of cases)
Cachexia	Occasional (present in 5%-29% of cases)
Cognitive impairment	Occasional (present in 5%-29% of cases)
Corneal dystrophy	Occasional (present in 5%-29% of cases)
Dental malocclusion	Occasional (present in 5%-29% of cases)
Dilatation of the ascending aorta	Occasional (present in 5%-29% of cases)
Ectopia lentis	Occasional (present in 5%-29% of cases)
Epicanthus	Occasional (present in 5%-29% of cases)
Fatigue	Occasional (present in 5%-29% of cases)
Genital hernia	Occasional (present in 5%-29% of cases)
Inguinal hernia	Occasional (present in 5%-29% of cases)
Keratoglobus	Occasional (present in 5%-29% of cases)
Kyphosis	Occasional (present in 5%-29% of cases)
Long thorax	Occasional (present in 5%-29% of cases)
Microcornea	Occasional (present in 5%-29% of cases)
Microdontia	Occasional (present in 5%-29% of cases)
Migraine	Occasional (present in 5%-29% of cases)
Muscular hypotonia	Occasional (present in 5%-29% of cases)
Myopia	Occasional (present in 5%-29% of cases)
Open bite	Occasional (present in 5%-29% of cases)
Osteoarthritis	Occasional (present in 5%-29% of cases)
Papule	Occasional (present in 5%-29% of cases)
Pes planus	Occasional (present in 5%-29% of cases)
Pneumothorax	Occasional (present in 5%-29% of cases)
Reduced consciousness/confusion	Occasional (present in 5%-29% of cases)
Reduced number of teeth	Occasional (present in 5%-29% of cases)
Retinal detachment	Occasional (present in 5%-29% of cases)
Urticaria	Occasional (present in 5%-29% of cases)
Wide nasal bridge	Occasional (present in 5%-29% of cases)
Aortic root dilatation	-
Autosomal dominant inheritance	-
Bowel diverticulosis	-
Cigarette-paper scars	-
Fragile skin	-
Hyperextensibility at elbow	-
Hyperextensibility of the finger joints	-
Hyperextensibility of the knee	-
Infantile muscular hypotonia	-
Irregularly spaced teeth	-
Lop ear	-
Molluscoid pseudotumors	-
Narrow maxilla	-
Poor wound healing	-
Premature birth following premature rupture of fetal membranes	-
Soft skin	-
Subcutaneous spheroids	-

Last updated: 9/1/2017

Cause Cause

More than 90% of people affected by classical EDS have an identifiable mutation in the COL5A1 gene or the COL5A2 gene that is known to cause the condition.^[2] These genes provide instructions for making different components of type V collagen. Collagen is a protein that provides structure and strength to connective tissues throughout the body. Mutations in COL5A1 or COL5A2 lead to defects in the structure and function of type V collagen molecules. This causes the many signs and symptoms associated with classical EDS.^[5]^[6]

In rare cases, mutations in the genes encoding type I collagen (COL1A1 gene) can be found in people with classical EDS.^[3]

Last updated: 6/30/2017

Inheritance Inheritance

Classical EDS is inherited in an autosomal dominant manner.^[2] This means that to have the syndrome, a person needs a mutation in only one copy of the known disease-causing genes in each cell. In some cases, a person with classical EDS inherits the mutation from a parent with the syndrome. 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 classical EDS has a 50% chance with each pregnancy of passing along the mutated gene to his or her child.

Last updated: 6/30/2017

Diagnosis Diagnosis

A diagnosis of classical EDS is typically based on the presence of characteristic signs and symptoms. More than 90% of classical EDS patients have mutations in one of the genes encoding type V collagen (the COL5A1 gene or the COL5A2 gene). Rare cases are caused by a mutation in the COL1A1 gene. Genetic testing for a mutation in these genes can then be ordered to confirm the diagnosis in some cases.^[1]^[2]

Collagen typing performed on a skin biopsy may be recommended if genetic testing is not available or inconclusive. Transmission electron microscopy (TEM) (a very powerful microscopy) findings of collagen flowers on skin biopsy can support the clinical diagnosis, but cannot confirm it. 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. Although this test is generally not helpful in confirming a diagnosis of classical EDS, it can be used to rule out some of the other forms of EDS.^[2]

Absence of these findings does not rule-out the diagnosis of classical EDS; however, alternative diagnoses should be considered in the absence of a type V collagen gene mutation or electron microscopy findings.

Last updated: 6/30/2017

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.

Treatment Treatment

The treatment of classical EDS varies based on the signs and symptoms present in each person. For example, children with hypotonia and/or delayed motor milestones may benefit from physical therapy and occupational therapy. These treatments can also help improve joint stability. Assistive devices such as braces may also be necessary depending on the severity of joint instability. Anti-inflammatory medications may be prescribed for joint pain. Because classical EDS is associated with fragile skin with abnormal wound healing, people with the syndrome, especially children, may need to wear protective bandages or pads over exposed areas, such as the knees, shins, and forehead. Children and adolescents may be monitored for the development of aortic root dilatation (enlargement of the blood vessel that distributes blood from the heart to the rest of the body).^[2]^[4]

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

Last updated: 6/30/2017

Management Guidelines

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.

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

The U.S. National Institutes of Health, through the National Library of Medicine, developed ClinicalTrials.gov to provide patients, family members, and members of the public with current information on clinical research studies. There are currently trials regarding connective tissue disorders. To see these trials, click on the link above.
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

Ehlers-Danlos Society
PO Box 87463
Montgomery Village, MD 20886
Telephone: 410-670-7577
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
Hypermobility Syndromes Association (HMSA)
49 Greek Street
London, WD1 4EG United Kingdom
Telephone: 03330 116 388
E-mail: http://hypermobility.org/contact-us/
Website: http://hypermobility.org/
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).

Organizations Providing General Support

Coalition for Heritable Disorders of Connective Tissue
4301 Connecticut Avenue, NW
Suite 404
Washington, DC 20008
Website: chdct.org

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.

Genetics Resources

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 GeneTests, 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.

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 Classical Ehlers-Danlos syndrome. This website is maintained by the National Library of Medicine.
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 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
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.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Classical Ehlers-Danlos syndrome. Click on the link to view a sample search on this topic.

News & Events News & Events

News

Don’t Miss the NCATS Toolkit for Patient-Focused Therapy Development Event
August 31, 2017
Funding Opportunities Now Available for the Undiagnosed Diseases Network (UDN) Phase II
August 30, 2017
IRDiRC Goals 2017-2027: New Rare Disease Research Goals for the Next Decade
August 10, 2017

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 Classical Ehlers-Danlos syndrome. If you have a question about any of these diseases, you can contact GARD.

Ehlers-Danlos syndromes

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Is there a proanthocyanidin that is particularly helpful for Ehlers-Danlos syndrome, classic type? I want to support my body's ability to make stronger collagen. See answer

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References References

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.
Fransiska Malfait, MD, PhD, Richard Wenstrup, MD, and Anne De Paepe, MD, PhD. Ehlers-Danlos Syndrome, Classic Type. GeneReviews. August 2011; http://www.ncbi.nlm.nih.gov/books/NBK1244/.
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.
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.
COL5A1. Genetics Home Reference. May 2006; http://ghr.nlm.nih.gov/gene/COL5A1.
COL5A2. Genetics Home Reference. May 2006; http://ghr.nlm.nih.gov/gene/COL5A2.