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Classic Ehlers-Danlos Syndrome

Last updated Aug. 14, 2018

Approved by: Krish Tangella MD, MBA, FCAP

Classic Ehlers-Danlos Syndrome (or Classic EDS) is a hereditary connective tissue disorder caused by abnormalities in the formation of collagen, an important and the most abundant protein in the body.


What are the other Names for this Condition? (Also known as/Synonyms)

  • Classic EDS
  • EDS, Classic Type
  • Ehlers-Danlos Syndrome, Classic Type

What is Classic Ehlers-Danlos Syndrome? (Definition/Background Information)

  • Classic Ehlers-Danlos Syndrome (or Classic EDS) is a hereditary connective tissue disorder caused by abnormalities in the formation of collagen, an important and the most abundant protein in the body
    • Connective tissue is made up of structural proteins known as collagens and fibroblast cells, which are arranged in rows
    • These tissues connect bone-bone and muscle-bone, and give strength, support, and elasticity to various structures of the body, like skin, joints, and walls of blood vessels
    • There are 3 types of connective tissue, namely, tendons, ligaments and cartilages
  • The Classic Type of Ehlers-Danlos Syndrome is caused by COL5A1 or COL5A2 gene mutations. These genes code for 2 different alpha chains of the collagen type V protein. A mutation in either gene interferes with the assembly of the collagen V protein, and thus with the collagen matrix, resulting in the symptoms of the disorder
  • In many cases, the gene mutations are inherited in an autosomal dominant manner, in which a single copy of the affected gene is every cell of an individual is sufficient to cause Classic EDS. Individuals with this type of EDS, inherit the condition from an affected parent
  • Extreme joint flexibility, susceptibility for joint dislocations, loose skin, low muscle tone, formation of tumor-like growths on the skin, and a tendency to bruise easily, are some symptoms of Classic Ehlers-Danlos Syndrome
  • The diagnosis of Classic EDS is made by conducting a variety of exams including a physical examination, symptom assessment, evaluation of family medical history, collagen typing, and molecular genetic testing to ascertain gene mutations
  • Premature arthritis, delayed achievement of developmental milestones, aortic root dilatation, and wound healing difficulties are some potential complications of this disorder
  • The treatment options for Classic EDS involve medications for pain and blood pressure, physical therapy, and surgery to correct bone dislocations. The prognosis of Classic Ehlers-Danlos Syndrome depends on the severity of symptoms and overall health of the affected individual. In most cases, individuals have a normal life span and intelligence

Who gets Classic Ehlers-Danlos Syndrome? (Age and Sex Distribution)

  • Classic Ehlers-Danlos Syndrome occurs worldwide, with a frequency between 1:20,000 and 1:40,000
  • The onset of the disorder can occur at birth, or manifest later in life. Individuals with milder symptoms are typically diagnosed in adulthood
  • There is no gender, ethnic, or racial bias in the occurrence of this disorder

What are the Risk Factors for Classic Ehlers-Danlos Syndrome? (Predisposing Factors)

The following are some known risk factors for Classic Ehlers-Danlos Syndrome:

  • A family history of the disorder
  • Having parents, who are close blood relatives (such as first cousins)

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Classic Ehlers-Danlos Syndrome? (Etiology)

  • Classic Ehlers-Danlos Syndrome is caused by mutation(s) in either the COL5A1 or COL5A2 gene
    • Under normal circumstances, these 2 genes code for two different types of alpha chains of collagen type V, a ubiquitous protein, which is a type of fibrillar-forming collagen
    • The proper assembly of this protein ensures the formation of the collagen matrix, which renders the connective tissue strong and flexible
    • When either of these genes is mutated, it may lead to structural and/or functional abnormalities of the collagen V protein. This in turn can compromise the integrity of the collagen matrix, leading to development of the symptoms
  • Classic EDS is inherited in an autosomal dominant manner. In this type of inheritance, a single copy of a defective gene in every cell of an individual is sufficient to cause disease. Typically, one inherits the disorder from an affected parent
  • In some cases, an individual can develop Classic EDS with no family history of the condition. This can occur owing to sporadic mutation(s) in either of the causative genes. The exact cause of such mutations is not known

What are the Signs and Symptoms of Classic Ehlers-Danlos Syndrome?

The presentations of Classic Ehlers-Danlos Syndrome may vary in type and severity among the affected individuals. The following are the signs and symptoms of Classic EDS:

  • Presence of loose, elastic skin; abnormally-thin skin, or smooth “velvety” skin
  • “Cigarette paper” scars i.e., scarring of skin owing to abnormal healing of wounds
  • Formation of hard lumps under the skin, called calcified spheroids. These lumps are mobile and can move easily beneath the skin
  • Degeneration and parchment-like (papyraceous) scarring of skin, which may expand
  • Tumor-like growths on skin, called molluscoid pseudotumors
  • A tendency to bruise easily; repeated bruising in the same location
  • Loose joints (laxity of joints); overly-flexible joints i.e., a range of joint movement beyond what is normally observed
  • Joint pain; vulnerability to joint dislocations
  • A tendency to develop early-onset osteoarthritis
  • Thin, fragile blood vessels, may predispose an individual to hemorrhages
  • Fragile internal organs and other tissues; prolapse or shifting of internal organs
  • Flat feet
  • Low muscle tone (hypotonia)
  • Hiatal hernia or protrusion of a part of stomach through the diaphragm wall
  • Deformed mitral valve in the heart
  • Dilated aorta, in rare cases
  • Complications after surgery, which may include the following:
    • Hernia due to weak tissues and membranes
    • Opening of the surgical site wound, owing to separation of tissues (dehiscence)

How is Classic Ehlers-Danlos Syndrome Diagnosed?

The diagnosis of Classic Ehlers-Danlos Syndrome is undertaken with the help of the following tests and exams:

  • A thorough physical examination and an assessment of symptoms
  • An evaluation of personal and family medical history
  • Measurement of skin hyperextensibilty, by pulling up skin, till resistance is registered
  • Beighton scale hypermobility testing for joints: This operates on a 9-point system; a score of over 6 may indicate hypermobility
  • Collagen typing using a skin biopsy sample
  • Collagen skin mutation testing
  • Electron microscopic observation of a skin sample
  • Imaging tests such as X-ray, computed tomography (CT) scanning, or magnetic resonance imaging (MRI):
    • To visualize loss of bone mass
    • For structural abnormalities of the heart, along with echocardiography
    • To monitor aneurysm
  • Genetic testing to confirm mutations in genes that cause EDS

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Classic Ehlers-Danlos Syndrome?

The following are some potential complications in individuals with Classic Ehlers-Danlos Syndrome:

  • Bruising of skin (often at the same locations) and permanent scarring
  • Disintegration of scar tissue
  • Repeated joint dislocations
  • Early-onset arthritis
  • Developmental delays
  • Delayed wound healing
  • Spontaneous rupture of blood vessels
  • Aortic root dilatation (enlargement of the aorta)
  • Mitral valve regurgitation (blood flowing back into the heart)
  • Progressive loss of motor function
  • Uterine or arterial rupture during pregnancy
  • Uterine rupture at childbirth

How is Classic Ehlers-Danlos Syndrome Treated?

The treatment for Classic Ehlers-Danlos Syndrome is symptomatic, as there is no cure for the disorder. Often, a coordinated effort by professionals from various specialties may be needed to help the affected individual achieve a certain quality of life.

The following are some measures for treating the symptoms of Classic EDS:

  • Medications for pain relief: The strength of medication administered depends on the severity of pain
  • Medications, to reduce blood pressure (necessitated by fragile blood vessels), such as the following:
    • Beta blockers
    • Angiotensin-converting enzyme inhibitors
    • Calcium channel blockers
    • Diuretic pills
  • Proper and balanced nutrition
  • Vitamin C supplements may be recommended to aid in collagen synthesis and wound healing
  • Physiotherapy to strengthen muscles around weak joints
  • Braces to stabilize joints and minimize dislocations
  • Rarely, surgery to repair joints damaged by repeated dislocations may be performed, if necessary

How can Classic Ehlers-Danlos Syndrome be Prevented?

Classic Ehlers-Danlos Syndrome is a genetic disorder, and currently, there are no methods or guidelines available to prevent its occurrence.

  • Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
  • If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
  • In individuals who are diagnosed with Classic EDS, the following may be helpful in reducing injuries, dislocations, and bleeding:
    • Avoiding contact sports and other activities that may cause injury
    • Wearing padding over joints that are vulnerable to dislocation
    • Avoiding unnecessary surgical procedures, since wound healing may be compromised
    • If surgery or dental procedures become necessary, then taking precautions against bleeding before, during, and after the procedure or surgery
    • Proper counseling and medical care for women before and during pregnancy, as well as during and after childbirth 
  • Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as Classic Ehlers-Danlos Syndrome

Regular medical screening at periodic intervals with tests, and physical examinations are crucial and are highly recommended.

What is the Prognosis of Classic Ehlers-Danlos Syndrome? (Outcomes/Resolutions)

  • The prognosis of Classic Ehlers-Danlos Syndrome is determined by the severity of the condition and the overall health of the affected individual. The life expectancy of individuals with this disorder is reported to be normal
  • However, since there is no cure for Classic EDS, a lifelong management of the condition with medication, physiotherapy, and other supportive measures are often necessary to have an improved quality of life

Additional and Relevant Useful Information for Classic Ehlers-Danlos Syndrome:

Please visit our Congenital & Genetic Disorders Health Center for more physician-approved health information:

http://www.dovemed.com/diseases-conditions/congenital-genetic-disorders/

What are some Useful Resources for Additional Information?


References and Information Sources used for the Article:


Helpful Peer-Reviewed Medical Articles:


Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: April 7, 2017
Last updated: Aug. 14, 2018