Ehlers–Danlos syndrome

The Ehlers -Danlos syndrome ( EDS) is a heterogeneous group of inborn errors of connective tissue, which is mainly characterized by a hyperextensibility skin and articulated joints. But also affects vessels, muscles, ligaments, tendons and internal organs.

In some types of EDS one goes from the cause of a defective collagen, which is responsible for elasticity and cohesion. For other types, the causes are still unclear. The frequency of occurrence in the population is assumed to be 1:5,000 to 1:10,000. There are no differences in the incidence between different ethnic groups or genders.

Other names for EDS:

• Ehlers -Danlos Meekeren syndrome, Ehlers-Danlos syndrome - Meekeren, Van Meekeren 's syndrome
• Danlos ' syndrome
• Fibrodysplasia elastica generalisata cutis hyperelastica
• Dermatolysis
• Rubber skin, Indian rubber skin
• Laxité articulaire congenital
• Chernogubov 's syndrome, Tschernogubow syndrome
• Sack 's syndrome, bag - Barabas syndrome

History

It is one of the oldest known causes of bruising and bleeding, which have already been recognized by Hippocrates 400 BC. A first case study with abnormal skin elasticity of a Spanish man is known by the Dutch surgeon Job Janzoon of Meerkerin 1668. The first comprehensive description of the syndrome with its many facets ( skin, joints, scars, etc. ) was created in 1891 by the Russian dermatologists Tschernogubow. However, the isolated Zarenreich prevented the general announcement of the study, so that Edvard Ehlers with the description of the essential connections with the proposal, the hyperextensibility and -cleavage to nominate in 1901 and Henri -Alexandre Danlos 1908, the skin as cardinal symptoms, the namesake of the syndrome have been.

Classification

An EDS classification was attempted in the late 1960s. 1986 was defined then ten types which were published in 1988 at a conference in Berlin. With advancing knowledge on the molecular and biochemical field EDS in 1997 was re- divided. The new Villefranche classification served a simplified clinical diagnosis of Ehlers -Danlos syndrome and the delineation of disorders that overlap with the EDS ( see table). It could be now describe the disease by six types with their major and minor criteria. In addition, there are other, more exotic forms of EDS in individual cases.

There is a wide variability and overlap in symptoms between the different types, although the characteristics back to the collagen specifically affected. A unique classification is possible only on the basis of clinical diagnostics and genetic tests or skin biopsies.

The causing mutations were ( with the exception of a few exotic types and hypermobile cases) identified.

Methylenetetrahydrofolate reductase Methylenetetrahydrofolate reductase ( MTHFR short ) plays an important role in the methylation of the body, is particularly involved in the metabolism of B6, B12, folic acid. Mutations in this gene are associated with several diseases in conjunction, particularly neural tube defects, homocystinuria, and it is speculated that it may also lead to a phenotype of Ehlers -Danlos syndrome. More details on this is not known, but it showed mutations in this gene in families with the Ehlers -Danlos syndrome.

Prevalence

A disease or disorder is defined as rare in Europe when it is less than one in two thousand people affected by it. EDS as a group is one of the rare diseases at a rate of 1:5,000 to 1:10,000 approx.

In the classical type of EDS the incidence is estimated to be approximately 1:25,000. The hypermobile type of EDS with an estimated incidence of 1:10,000 the most common type of EDS. In the vascular type is expected incidence of 1:50,000. The other three types of EDS are even more rare and occur only occasionally ( less than a hundred known cases per type worldwide).

The types I II, III, IV and VII are autosomal dominant hereditary, which means that a child has a 50 percent probability of inheritance when a parent has this disease. There are also the de novo = New mutations that may be present 50% here. The kyphoskoliotische and dermatosparaxis type ( VI, VII C) are autosomal recessive hereditary. Their children can only inherit the disease if both parents have this gene defect. Each type of EDS has "his" own malformation, that is, for example, that an interested party may inherit with vascular type of EDS his child no classical type of EDS.

It should be noted that all figures are purely frequency hypotheses. They rely only on registered cases. At present, in Germany about 5,000 people with EDS known, but it is expected with a high number of unreported cases.

Diagnosis and symptoms

• Differential diagnoses
• Marfan syndrome Q87.4
• Osteogenesis imperfecta Q87.0
• Stickler syndrome Q87.8
• Achondroplasia ( chondrodysplasia ) Q77.4
• Rheumatoid arthritis M06
• M79.7 fibromyalgia
• Multiple sclerosis G35
• Hypermobility syndrome
• Growing pains

The diagnosis of rare diseases in general and in particular EDS throws in practice on problems. According to a study in 2005 were, for example, about 25 % of those affected their EDS diagnosis only 28 years after the onset of symptoms.

For an EDS diagnosis Erstformulierung a clinical suspicion is crucial. What matters is the presence of the main criteria after Villefrache classification ( see above), which is a high sensitivity for the disease. In addition, minor criteria and a positive family history corroborate the clinical diagnosis. In practice, the design, however, often different. Most are various symptoms that are unusual in combinations, severity and frequency of occurrence, and thus initiate the search for an explanatory cause. The ignorance of much of the medical profession leaves the sufferers often experience a year-long odyssey to diagnosis.

Pathologies by sector ( incomplete):

Pain The muskoloskeletale pain as a diagnostic criterion necessary because of the relevance of a more detailed consideration. Severe pain are common in all types of Ehlers -Danlos syndrome. Studies have found that chronic pain from the regular use of analgesics and quality of sleep depend that they occur more frequently and more in the hypermobile type and that the strength correlates with the hypermobility, the incidence of dislocations and previous surgical operations. Pain results in functional limitations in daily life, regardless of fatigue Fatigue.

EDS hypermobile type vs. Hypermobility syndrome: Currently, the clinical criteria that apply to the hypermobility syndrome and for the hypermobile variant of EDS, non-specific and non-exclusive for both parties. Therefore, some doctors and scientists are of the opinion that the hypermobility syndrome is a mild variant of the hypermobile type of EDS.

Therapy

For the Ehlers -Danlos syndrome, there is no cure. Patients with vascular type are considered most at risk and should be under constant medical supervision. The medical intervention for all EDS types is limited to symptomatic therapy, which can list them in a series of recommendations.

A monitoring of the cardiovascular system, physical therapy, occupational consideration, orthopedic aids, such as orthotics, bandages and wheelchairs can be helpful. Activities with hyperextension or blocking of the joints should be avoided.

Necessary surgical procedures should be performed with caution. For any necessary anesthetic technique there are several possible difficulties such as difficult airway situations, susceptibility to vascular tears when the system of central venous catheters and massive bleeding events especially in Bagatelloperationen at EDS patients with fragile vessels. An implementation of operational procedures should only be performed in centers with sufficient expertise in the treatment of EDS. Bänderraffungen or similar. often do not lead to the desired success for joint stabilization. In the physiotherapy posture training and stability exercises should be consistent with the structure of the small muscles responsible for this in the foreground.

With bandages the most sensitive areas can be protected from injury. Some patients respond to the administration of vitamin C with reduced swelling tendency and improved wound healing. Experiments with bio-engineered skin substitute in non-healing wounds were successful in individual patients.

Children should be provided with information about EDS so they can understand why contact sports or other stressful pastimes should be avoided. It is also important to promote the attitude control early in order to prevent damage caused by poor posture. Family members, teachers and friends should also be actively informed so that they can accept the child and promote if necessary.

Emotional support, behavior therapy and psychological support to help those affected of all subtypes to accept the handicap or better cope with it. Patient organizations can assist (see links).

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Forecast

The outlook for people with EDS depends on the type with which they have been diagnosed. Symptoms vary even within the subtypes and the incidence of complications from patient to patient. Some have only minor restrictions, while others are severely limited by the severity in daily life. Extreme joint instability, pain and spinal deformation can severely limit mobility. Most patients have a normal life expectancy. However, patients with vascular involvement are exposed to an increased risk of serious complications.

EDS is a lifelong condition with mostly progressive course. Affected faced because of their illness with social obstacles. Some patients report fears of serious and painful ruptures, prior to the aggravation of the condition of unemployment because of their physical and emotional burdens as well as against social exclusion in general. A gene therapy or other approaches to healing are not in sight, studies to date have not been known.