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Genetics of Ehlers-Danlos Syndrome

Practice Essentials

Ehlers-Danlos syndrome (EDS) consists of a group of inherited heterogeneous disorders that share a common decrease in the tensile strength and integrity of the skin, joints, and other connective tissues.
This group of connective-tissue disorders is characterized by abnormal collagen synthesis causing hyperextensibility of the skin, hypermobility of the joints,
and tissue fragility, as is seen by easy bruising and delayed wound healing with atrophic scarring.
 Depending on the type, EDS can be diagnosed through laboratory studies or clinical examination. Once the syndrome has been diagnosed, preventative measures should be taken.

People with lax joints and multiple scars were first described in the medical writings of Hippocrates, dating back to 400 BCE.
In 1892, Dr. A. Tschernogobow, a Russian dermatologist, presented two case studies of patients who had marked loose, fragile skin and hypermobile large joints, to the Moscow Venereology and Dermatology Society. His work provides the first detailed clinical description of EDS.

The syndrome derives its name from additional clinical case reports presented by two physicians: Edvard Ehlers, a Danish dermatologist, in 1901, and Henri-Alexandre Danlos, a French physician with expertise in chemistry of skin disorders, in 1908. Both physicians combined the pertinent features of the syndrome and accurately delineated the phenotypic features of this group of inherited disorders. The name, Ehlers-Danlos syndrome, was coined in 1936.

Some patients with EDS can demonstrate amazing, almost unnatural, contortions, often arousing the curiosity of onlookers. Niccolo Paganini (1782-1840) the famous Italian violinist, who was capable of miraculous feats in his playing owing to his hypermobile and loose joints, had phenotypic traits of EDS.
In the late 19th century, historians described performers with traits of EDS who displayed their hyperextensible maneuvers publicly in circuses and travelling shows. Some achieved celebrity status, acquiring titles such as “The India Rubber Man,” “The Elastic Lady,” and “The Human Pretzel.”

Patients displaying clinical capabilities such as these raise suspicion of the diagnosis when identified on physical examination. Unfortunately, patients with EDS are often not diagnosed for many years.
Examples of hyperextensibility and hypermobility are shown in the following images.

Patient with Ehlers-Danlos syndrome. Note the abno

Patient with Ehlers-Danlos syndrome. Note the abnormal ability to elevate the right toe. Courtesy of Enrico Ceccolini, MD.

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Girl with Ehlers-Danlos syndrome. Dorsiflexion of

Girl with Ehlers-Danlos syndrome. Dorsiflexion of all the fingers is easy and absolutely painless. Courtesy of Enrico Ceccolini, MD.

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Patient with Ehlers-Danlos syndrome mitis. Joint h

Patient with Ehlers-Danlos syndrome mitis. Joint hypermobility is less intense than with other conditions. Courtesy of Enrico Ceccolini, MD.

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Signs and symptoms of Ehlers-Danlos syndrome

All EDS types share the following cutaneous features:

Loose, hyperextensible, fragile skin

Poor wound healing

Tendency to bruise easily

Atrophic scars that are wide and thin, known as “cigarette paper scars”

The following extracutaneous features are also shared:

Fragility of blood vessels

Hyperextensible, hypermobile joints

Propensity for spontaneous joint dislocations/subluxations

Workup in Ehlers-Danlos syndrome

The following laboratory studies may be indicated in patients diagnosed with EDS:

Diagnosis of the vascular-type EDS (type IV), arthrochalasia-type EDS (types VIIA and VIIB), and dermatosparaxis-type EDS (type VIIC) requires a skin biopsy; biochemical studies performed on cultured skin fibroblasts can detect alterations in collagen molecules

Molecular (DNA-based) testing is available for the vascular, arthrochalasia, and dermatosparaxis types

Kyphoscoliosis-type EDS (type VI) can be identified by urine enzyme assay

The remaining types of EDS—classical-type EDS and hypermobility-type EDS—are diagnosed through clinical examination.

Management

Recommend low-resistance exercise for patients with EDS to help increase muscle tone and stabilize loose joints. Physical therapy guided by a therapist who is experienced in working with patients with connective-tissue abnormalities and joint dysfunction can be very helpful in the management of long-term health.

Instruct patients with EDS to avoid excessive or repetitive heavy lifting and other movements that produce undue strain or stress on their already hypermobile joints (eg, finger hyperextension that occurs with pushing off of a wall with the palms of the hands).
Advise patients to minimize joint trauma by avoiding joint hyperextension or joint locking.

Surgery may be indicated to correct fractures and stabilize dislocated joints. Preferential use of staples or tape (rather than stitches) for wound closure should be strongly considered.

Comprehensive, accurate genetic counseling is one of the most critical issues in the treatment of patients with EDS. Provide the family with detailed information regarding EDS’s inheritance pattern and recurrence risks, as well as identification of at-risk family members. Screen pertinent individuals in the family for subtle signs and symptoms of the condition, regardless of whether signs or symptoms are suggested by family history.

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