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

This disease is grouped under:

Ehlers-Danlos syndromes

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

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Abnormal nasal morphology	Abnormal of nasal shape Abnormal of shape of nose [ more ]	0005105
Abnormality of the gingiva	Abnormality of the gums	0000168
Abnormality of the tongue	Abnormal tongue Tongue abnormality [ more ]	0000157
Arachnodactyly	Long slender fingers Spider slender fingers [ more ]	0001166
Arterial dissection		0005294
Asthma		0002099
Atypical scarring of skin	Atypical scarring	0000987
Eczema		0000964
Emphysema		0002097
Glaucoma		0000501
High, narrow palate	Narrow, high-arched roof of mouth Narrow, highly arched roof of mouth [ more ]	0002705
Hyperextensible skin	Hyperelastic skin Skin hyperelasticity Stretchable skin [ more ]	0000974
Hyperlordosis	Prominent swayback	0003307
Hypertension		0000822
Hypotension	Low blood pressure	0002615
Joint hyperflexibility	Joints move beyond expected range of motion	0005692
Malar prominence	Cheekbone prominence	0010620
Pectus carinatum	Pigeon chest	0000768
Petechiae		0000967
Shagreen patch		0009721
Spina bifida occulta		0003298
Striae distensae	Stretch marks	0001065
Triangular face	Face with broad temples and narrow chin Triangular facial shape [ more ]	0000325
30%-79% of people have these symptoms
Acrocyanosis	Persistent blue color of hands, feet, or parts of face	0001063
Aplasia/Hypoplasia of the abdominal wall musculature	Absent/small abdominal wall muscles Absent/underdeveloped abdominal wall muscles [ more ]	0010318
Bruising susceptibility	Bruise easily Easy bruisability Easy bruising [ more ]	0000978
Erythema		0010783
Hiatus hernia	Stomach hernia	0002036
Hypoplasia of the ear cartilage	Underdeveloped ear cartilage	0100720
Joint dislocation	Joint dislocations Recurrent joint dislocations [ more ]	0001373
Mitral valve prolapse		0001634
Muscle weakness	Muscular weakness	0001324
Myalgia	Muscle ache Muscle pain [ more ]	0003326
Narrow face	Decreased breadth of face Decreased width of face [ more ]	0000275
Premature birth	Premature delivery of affected infants Preterm delivery [ more ]	0001622
Scoliosis	Abnormal curving of the spine	0002650
Thin skin		0000963
Tricuspid valve prolapse		0001704
Umbilical hernia		0001537
Venous insufficiency		0005293
5%-29% of people have these symptoms
Abnormality of the renal tubule		0000091
Ascending tubular aorta aneurysm	Bulging of wall of large artery located above heart	0004970
Atrial septal defect	An opening in the wall separating the top two chambers of the heart Hole in heart wall separating two upper heart chambers [ more ]	0001631
Blue sclerae	Whites of eyes are a bluish-gray color	0000592
Cachexia	Wasting syndrome	0004326
Cognitive impairment	Abnormality of cognition Cognitive abnormality Cognitive defects Cognitive deficits Intellectual impairment Mental impairment [ more ]	0100543
Corneal dystrophy		0001131
Dental malocclusion	Bad bite Malalignment of upper and lower dental arches Misalignment of upper and lower dental arches [ more ]	0000689
Ectopia lentis		0001083
Epicanthus	Eye folds Prominent eye folds [ more ]	0000286
Fatigue	Tired Tiredness [ more ]	0012378
Genital hernia		0100823
Inguinal hernia		0000023
Keratoglobus		0001119
Kyphosis	Hunched back Round back [ more ]	0002808
Long thorax	Long rib cage	0100818
Microcornea	Cornea of eye less than 10mm in diameter	0000482
Microdontia	Decreased width of tooth	0000691
Migraine	Intermittent migraine headaches Migraine headache Migraine headaches [ more ]	0002076
Muscular hypotonia	Low or weak muscle tone	0001252
Myopia	Close sighted Near sighted Near sightedness Nearsightedness [ more ]	0000545
Open bite	Absence of overlap of upper and lower teeth Open bite between upper and lower teeth [ more ]	0010807
Osteoarthritis	Degenerative joint disease	0002758
Papule		0200034
Pes planus	Flat feet Flat foot [ more ]	0001763
Pneumothorax	Collapsed lung	0002107
Reduced consciousness/confusion	Disturbances of consciousness Lowered consciousness [ more ]	0004372
Reduced number of teeth	Decreased tooth count	0009804
Retinal detachment	Detached retina	0000541
Short stature	Decreased body height Small stature [ more ]	0004322
Urticaria	Hives	0001025
Wide nasal bridge	Broad nasal bridge Broad nasal root Broadened nasal bridge Increased breadth of bridge of nose Increased breadth of nasal bridge Increased width of bridge of nose Increased width of nasal bridge Nasal bridge broad Wide bridge of nose Widened nasal bridge [ more ]	0000431
Percent of people who have these symptoms is not available through HPO
Aortic root aneurysm	Bulge in wall of root of large artery that carries blood away from heart	0002616
Autosomal dominant inheritance		0000006
Bowel diverticulosis		0005222
Cigarette-paper scars	'cigarette paper scarring' Cigarette paper scarring [ more ]	0001073
Fragile skin	Skin fragility	0001030
Hyperextensibility at elbow		0010485
Hyperextensibility of the finger joints	Finger joint hyperextensibility Hyperextensible digits Hyperextensible finger [ more ]	0001187
Hyperextensibility of the knee		0010500
Infantile muscular hypotonia	Decreased muscle tone in infant	0008947
Irregularly spaced teeth	Irregular dental spacing Variability of spacing between teeth [ more ]	0006316
Lop ear		0000394
Molluscoid pseudotumors		0000993
Narrow maxilla	Decreased breadth of upper jaw bones Decreased width of upper jaw bones Narrow upper jaw bones [ more ]	0002010
Poor wound healing		0001058
Premature birth following premature rupture of fetal membranes		0005100
Soft skin		0000977
Subcutaneous spheroids		0025014

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 11/1/2018

Do you have updated information on this disease? We want to hear from you.

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

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 Classical Ehlers-Danlos syndrome. 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.
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 , https://www.ehlers-danlos.com/eds-helpline/
Website: https://www.chronicpainpartners.com/contact-us/
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 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

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.
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

The NIH Undiagnosed Diseases Network Expands
September 26, 2018

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

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.