Ehlers-Danlos syndrome – general

Synonyms

1

Overview

Ehlers-Danlos syndrome is a group of disorders that affect the connective tissues that support the skin, bones, blood vessels, and many other organs and tissues. Defects in connective tissues cause the signs and symptoms of Ehlers-Danlos syndrome, which vary from mildly loose joints to life-threatening complications.

It is an inherited disorder estimated to occur in about 1 in 5,000 births worldwide. Ehlers–Danlos affects males and females of all racial and ethnic backgrounds, although some types are more common among certain groups than others. EDS is clinically heterogeneous; the underlying collagen abnormality is different for each type.

Previously, there were more than 10 recognized types of Ehlers-Danlos syndrome, differentiated by Roman numerals. In 1997, researchers proposed a simpler classification that reduced the number of major types to six and gave them descriptive names: the classical type (formerly types I and II), the hypermobility type (formerly type III), the vascular type (formerly type IV), the kyphoscoliosis type (formerly type VIA), the arthrochalasia type (formerly types VIIA and VIIB), and the dermatosparaxis type (formerly type VIIC). This six-type classification, known as the Villefranche nomenclature, is still commonly used. Most commonly occurring is the hypermobility type, followed by the classical type. The other types of Ehlers–Danlos syndrome are very rare. Clinical recognition of the types of EDS is important. One type, type IV, is associated with arterial rupture and visceral perforation, with possible life-threatening consequences.

Symptoms

EDS typically affects the joints, skin, and blood vessels. People who have Ehlers-Danlos syndrome usually have overly flexible joints and stretchy, fragile skin. Signs vary widely based on which type of EDS the patient has. In each case, however, the signs are ultimately due to faulty or reduced amounts of collagen. Following is a list of major signs and symptoms. Their severity can vary from person to person.

Musculoskeletal: 

  • Hyper-flexible joints: because the connective tissue that holds joints together is looser, your joints can move far past the normal range of motion. Small joints are affected more than large joints. It is possible to be very flexible or have "double joints", however, this is not the same as EDS. Unstable joints that are prone to sprain, dislocation, subluxation and hyperextension.
  • Thoracic outlet syndrome
  • Early onset of advanced osteoarthritis
  • Chronic degenerative joint disease
  • Swan neck deformity of the fingers
  • Boutonniere deformity of the fingers
  • Tearing of tendons or muscles
  • Deformities of the spine, such as scoliosis (curvature of the spine), kyphosis (a thoracic hump), tethered spinal cord syndrome, occipitoatlantoaxial hypermobility
  • Myalgia (muscle pain) and arthralgia (joint pain), which may be severe
  • Trendelenburg's sign
  • Osgood-Schlatter Disease

Skin:

  • Stretchy, fragile skin that tears easily: you may be able to pull a pinch of skin up away from your flesh, but it will snap right back into place when you let go. When damaged, skin often doesn't heal well. For example, the stitches used to close a wound often will tear out and leave a gaping scar.
  • Easy bruising
  • Redundant skin folds
  • Molluscoid pseudotumors, especially on pressure points
  • Subcutaneous spheroids
  • Livedo reticularis

Cardiovascular:

  • People who have the vascular subtype of Ehlers-Danlos syndrome often share distinctive facial features of a thin nose, thin upper lip, small earlobes and prominent eyes. They also have thin, translucent skin that bruises very easily. One of the most severe forms of the disorder, vascular Ehlers-Danlos syndrome can weaken your heart's largest artery (aorta), as well as the arteries to your kidneys and spleen. A rupture of any of these blood vessels can be fatal. Other vascular symptoms may include valvular heart disease such as mitral valve prolapse, which creates an increased risk for infective endocarditis during surgery, as well as possibly progressing to a life-threatening degree of severity of the prognosis of mitral valve prolapse.

Other manifestations or complications:

  • Hiatial hernia
  • Anal prolapse
  • Collapsed lung (pneumothorax)
  • Nerve compression disorders (carpal tunnel syndrome, acroparesthesia, neuropathy)
  • Insensitivity to local anesthetics
  • Arnold–Chiari malformation (brain disorder)
  • Platelet aggregation failure (platelets do not clump together properly)
  • Pregnancy complications - increased pain, mild to moderate peripartum bleeding, cervical insufficiency, uterine tearing, or premature rupture of membranes.
  • Sleep apnea

Because it is often undiagnosed or misdiagnosed in childhood, some instances of Ehlers–Danlos syndrome have been mischaracterized as child abuse.

The pain associated with this condition is a serious complication.

Causes

Some variations of Ehlers-Danlos can be caused by mutations that lead to disruption of the structure, production, or processing of collagen, the molecule that gives structure and strength to connective tissues throughout the body. Different subtypes of Ehlers-Danlos syndrome are associated with different underlying mutations, some of which are inherited and passed on from parent to child. If you have the most common varieties of Ehlers-Danlos syndrome, there's a 50 percent chance that you'll pass on the gene to each of your children.

Prevention

If you have a personal or family history of Ehlers-Danlos syndrome and you're thinking about starting a family, you may benefit from talking to a genetic counsellor — a health care professional trained to assess the risk of inherited disorders. Genetic counselling can help you understand the inheritance pattern of the type of EDS that affects you and the risks it poses for your children.

Diagnosis

Extremely loose joints, fragile or stretchy skin, and a family history of Ehlers-Danlos syndrome are often enough to make a diagnosis. Genetic tests on a sample of your blood can confirm the diagnosis in some cases and help rule out other problems.

Prognosis

The outlook for individuals with EDS depends on the type of EDS they have. Symptoms vary in severity, even within one sub-type, and the frequency of complications changes individually. Some people have negligible symptoms while others are severely restricted in their daily life. Extreme joint instability, chronic musculoskeletal pain, degenerative joint disease, frequent injuries, and spinal deformities may limit mobility. Severe spinal deformities may affect breathing. In the case of extreme joint instability, dislocations may result from simple tasks such as rolling over in bed or turning a doorknob.

Secondary conditions such as autonomic dysfunction or cardiovascular problems, occurring in any type, can affect prognosis and quality of life. Although all types are potentially life-threatening, the majority of individuals will have a normal lifespan. However, those with blood vessel fragility have a high risk of fatal complications. Arterial rupture is the most common cause of sudden death in EDS. Spontaneous arterial rupture most often occurs in the second or third decade, but can occur at any time. The median life-expectancy in the population with Vascular EDS is 48 years.

EDS is a lifelong condition. Affected individuals may face social obstacles related to their disease daily. Some people with EDS have reported living with fear of significant and painful ruptures, their condition worsening, becoming unemployed due to physical and emotional burdens, and social stigmatization in general.

Treatment

There is no cure for Ehlers Danlos Syndrome. Treatment is palliative. Close monitoring of the cardiovascular system, physiotherapy, occupational therapy, and orthopedic instruments (e.g., wheelchairs, bracing, casting) may be helpful. Orthopedic instruments are helpful for the prevention of further joint damage, especially for long distances, although it is advised that individuals not become dependent on them until there are no other options for mobility. One should avoid activities that cause the joint to lock or overextend. A physician may prescribe casting to stabilize joints. Physicians may refer a patient to an orthotist for orthotic treatment (bracing). Physicians may also consult a physical and/or occupational therapist to help strengthen muscles and to teach people how to properly use and preserve their joints. There are different types of physiotherapy. Aquatic therapy promotes muscular development and coordination. With manual therapy, the joint will be gently mobilized within the range of motion and/or manipulations. Electrotherapy like transcutaneous electrical nerve stimulation reduces local musculoskeletal pain. If conservative therapy is not helpful, surgical repair of joints may be necessary. Medication to decrease pain or manage cardiac, digestive, or other related conditions may be prescribed. To decrease bruising and improve wound healing, some patients have responded to ascorbic acid (vitamin C). Special precautions are often taken by medical care workers because of the sheer amount of complications that tend to arise in EDS patients. In Vascular EDS, signs of chest or abdominal pain are to be considered trauma situations.

In general, medical intervention is limited to symptomatic therapy. Before pregnancy, patients with EDS should have genetic counselling. Children with EDS should be provided with information about the disorder so they can understand why contact sports and other physically stressful activities should be avoided. Children should be taught early on that demonstrating the unusual positions they can maintain due to loose joints should not be done as this may cause early degeneration of the joints. Patients may find it hard to cope with the drawbacks of the disease. In this case emotional support and behavioral and psychological therapy can be useful. Support groups can be immensely helpful for patients dealing with major lifestyle changes and poor health. Family members, teachers, and friends should be informed about EDS so they can accept and assist the child.

Despite all these types of conservative therapy, except bracing, results show that conservative therapy is ineffective in contrast to midcarpal instability in normal patients. L. Rombaut showed that in almost 40% of the cases, conservative therapy has a neutral or even a negative outcome. Conservative therapy may be unsuccessful in controlling instability in the longer term.

Surgery:

The instability of joints, leading to (sub)luxations and joint pain, often require surgical intervention in patients with Ehlers-Danlos syndrome. Instability of almost all joints can happen but appear most often in the lower and upper extremities, with the wrist, fingers, shoulder, knee, hip, and ankle being most common.

Common surgical procedures are joint debridement, tendon replacements, capsulorraphy and arthroplasty. Studies have shown that after surgery, degree of stabilization, pain reduction, and patient satisfaction can improve, but surgery does not guarantee an optimal result: Patients and surgeons report being dissatisfied with the results. Consensus is that conservative treatment is more effective than surgery, particularly since patients have extra risks of surgical complications due to the disease. Three basic surgical problems arise due to EDS: the strength of the tissues is decreased, which makes the tissue less suitable for surgery; the fragility of the blood vessels can cause problems during surgery; and wound healing is often delayed or incomplete.

Studies have shown that local anesthetics, arterial catheters and central venous catheters cause a higher risk in haematoma formation in patients with Ehlers-Danlos syndrome. Ehlers-Danlos patients also show a resistance to local anaesthetics. Special recommendations for anesthesia in EDS patients are prepared by orphan anesthesia.eu and deal with all aspects of anesthesia for EDS patients. Detailed recommendations for anesthesia and perioperative care of patients with EDS should be used to improve patient safety.

Surgery with Ehlers-Danlos patients requires careful tissue handling and a longer immobilization afterward.

Resources

1. http://www.ncbi.nlm.nih.gov/gtr/conditions/C0013720/

2. https://en.wikipedia.org/wiki/Ehlers–Danlos_syndrome