Classical EDS (cEDS)

ESTIMATED PREVALENCE: 1 per 10,000 to 1 per 20,000 [12]

INHERITANCE PATTERN: Autosomal Dominant

SYMPTOMS [13, 14]:

There is a large amount of symptom variance in Classical EDS (cEDS) patients. Some may be severely affected, while others lead an “almost-normal” life. cEDS mainly affects the skin, tissue, and organs. Skin hyperextensibility and atrophic scarring (depressed scars) must be present for cEDS to be diagnosed. Skin hyperextensibility is defined as stretching the skin beyond 1.5cm.

Other cEDS symptoms include easily bruised skin, poor wound healing, skin fragility (tearing skin), “cigarette paper” scars from cuts/surgeries, velvety soft skin, and highly and unusually flexible joints (hypermobility). Sometimes those with cEDS are born with hypotonia (weak muscle tone) and delayed motor development may occur.

DIAGNOSTIC CRITERIA [15]:

To diagnose cEDS, the following formula must be satisfied:

Major Criterion #1 + Major Criterion #2, OR Major Criterion 1 + three (3) Minor Criteria

A patient must have Major Criterion #1 (Skin hyperextensibility and atrophic scarring), plus have either Major Criterion #2 (Generalized joint hypermobility (GJH) or have three Minor Criteria. Most cases of cEDS can then be confirmed using molecular genetic testing. However, some patients may have cEDS without having a specific genetic marker. Also, other types and subtypes of EDS can have “crossover” attributes of cEDS. This means that, for example, in addition to having Hypermobile EDS, an individual may have attributes of cEDS, although these attributes are usually milder than those with cEDS.

The major and minor criteria and the genetic markers responsible for cEDS can be found in the chart below.

Major Diagnostic Criteria

  1. Skin hyperextensibility and atrophic scarring
  2. Generalized joint hypermobility (GJH)

Minor Diagnostic 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, luxation/subluxation, pain, flexible flatfoot)
  9. Family history of a first-degree relative who meets clinical criteria

Genetic Markers:

Major: COL5A1, COL5A2 Rare: COL1A1