Classical Ehlers-Danlos Syndrome (cEDS)

cEDS is a genetic connective tissue disorder that causes severe skin hyperextensibility, skin fragility, and atrophic scarring. cEDS also causes joint hypermobility and joint instability.

cEDS is a rare disorder that affects roughly 1 in 20,000 – 40,000 people.

cEDS is caused by differences in the genes called genetic variants. These genetic variants affect the connective tissue, which provides support, protection, and structure throughout the body.

cEDS is caused by genetic variants of these genes:

  • COL5A1
  • COL5A2
  • COL1A1

cEDS is inherited in an autosomal dominant pattern. This means if a person inherits the genetic variant from one of their parents, they will have cEDS. Each child of a parent with cEDS will have a 50% chance of having cEDS.

About half of people with cEDS are the first person in their family to have cEDS due to a random mutation. Once a genetic variant is introduced through a random mutation, it can be inherited in an autosomal dominant pattern.

cEDS may be suspected if a person has:

  • Skin hyperextensibility
  • Skin fragility
  • Atrophic scarring
  • Poor wound healing
  • Easy bruising
  • Joint hypermobility
  • Joint instability
  • Pain
  • Unusual velvety or doughy skin texture

What is skin hyperextensibility? 

Skin hyperextensibility means that the skin can be stretched beyond the normal range. When released, hyperextensible skin returns to shape straight away. Skin extensibility is measured by pinching and lifting the skin on the volar (same side as the palm of the hand) surface at the middle of the non-dominant forearm. Skin is hyperextensible if it stretches greater than 1.5 cm. Skin hyperextensibility > 2 cm is usually present in people with cEDS.

What is atrophic scarring? 

Atrophic scars form when wounds heal at a lower level than the normal surface layer of the skin. This occurs when the skin does not regenerate tissue correctly and causes the scars to appear sunken. Papyraceous scars are atrophic scars that have widened to become paper-thin. Most people with cEDS have many atrophic and papyraceous scars on multiple areas of the body.

If a person meets the diagnostic criteria for cEDS, genetic testing should be done to confirm the diagnosis. Genetic testing is used to see if a person has the genetic variants that cause cEDS.

To meet the diagnostic criteria for cEDS, a person must meet:

  • Major criterion 1 AND major criterion 2


  • Major criterion 1 AND three or more minor criteria

Major Criteria 

  1. Skin hyperextensibility and atrophic scarring
  2. Generalized joint hypermobility

Minor Criteria

  1. Easy bruising
  2. Soft, doughy skin
  3. Skin fragility (or traumatic splitting)
  4. Molluscoid pseudotumors
  5. Subcutaneous spheroids
  6. Hernia (or history thereof)
  7. Epicanthal folds
  8. Complications of joint hypermobility (e.g., sprains, dislocations/subluxations, pain, flexible flatfoot)
  9. Family history of a first-degree relative who meets clinical criteria

cEDS is managed by addressing the symptoms a person is experiencing. cEDS can cause a variety of symptoms in many different areas of the body, so people with cEDS may require multiple providers in different specialties to manage their care. Key aspects of care focus on the skin and joints. People with cEDS should avoid unnecessary trauma and have wounds addressed properly. Each person should work with their care team to develop a care plan that meets their individual needs.

Sign up to The Ehlers-Danlos Society mailing list