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Disease Profile

Ehlers-Danlos syndromes

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Infancy

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ICD-10

Q79.6

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

ED syndrome; EDS; Ehlers Danlos syndrome

Categories

Connective tissue diseases

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/

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.

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.

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.

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

    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.

    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.

      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

        Social Networking Websites

        • The Ehlers-Danlos, Marfan and Related CTDs New England/MA Facebook Support Group offers educational and peer support through this forum.
        • 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).

          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

          • 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.
          • Genetics Home Reference (GHR) contains information on Ehlers-Danlos syndromes. This website is maintained by the National Library of Medicine.
          • 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.
            • 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 Ehlers-Danlos syndromes. Click on the link to view a sample search on this topic.

              References

              1. Defendi GL. Genetics of Ehlers-Danlos Syndrome. Medscape Reference. August, 2015; https://emedicine.medscape.com/article/943567-overview.
              2. Pauker SP & Stoler J. Clinical manifestations and diagnosis of Ehlers-Danlos syndromes. UpToDate. February 22, 2016; https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-ehlers-danlos-syndromes.
              3. 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.
              4. 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. https://onlinelibrary.wiley.com/doi/10.1002/ajmg.c.31552/full.
              5. EDS Types. The Ehlers-Danlos Society. March 16, 2017; https://ehlers-danlos.com/eds-types/.
              6. Ehlers-Danlos syndrome. Genetics Home Reference. November, 2015; https://ghr.nlm.nih.gov/condition=ehlersdanlossyndrome.
              7. Pauker SP & Stoler J. Overview of the management of Ehlers-Danlos syndromes. UpToDate. 2016; https://www.uptodate.com/contents/overview-of-the-management-of-ehlers-danlos-syndromes.
              8. 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.
              9. Ehlers-Danlos syndrome. Mayo Clinic. October 13, 2017; https://www.mayoclinic.org/diseases-conditions/ehlers-danlos-syndrome/diagnosis-treatment/drc-20362149.
              10. Ehlers Danlos Syndromes. National Organization for Rare Disorders (NORD). 2017; https://rarediseases.org/rare-diseases/ehlers-danlos-syndrome/.

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