Ehlers-Danlos syndrome

Definition

Ehlers-Danlos syndrome (EDS) refers to a group of disorders linked by genetic defects that affect collagen structure and function. Collagen is a major protein in the body and forms the base foundation for connective tissues. Owing to a genetic defect in collagen manufacture, tissues affected are abnormally weak, depending on the specific genetic defect. Major symptoms can include skin fragility, excessive skin stretchability, and excessively loose joints. Some types of EDS are characterized by fragile blood vessels or abnormal spine curvature.

Description

Collagen is a strong, fibrous protein that lends strength and elasticity to connective tissues such as the skin, tendons, organ walls, cartilage, and blood vessels. Each of these connective tissues requires collagen tailored to meet its specific purposes. The many roles of collagen are reflected in the number of genes dedicated to its production. There are at least 28 genes in humans that encode 16 different types of collagen. Defects in these genes can affect basic construction as well as the fine-tuned processing of the collagen.

According to the Ehlers-Danlos National Foundation, 1 in 5,000 to 1 in 10,000 people are affected by some form of EDS. EDS is an inherited disease, and its pattern depends on the affected gene. There are three types of inherited patterns: autosomal dominant, autosomal recessive, and X-linked (extremely rare).

Because chromosomes are inherited in pairs, each individual receives two copies of the same gene. (The sex chromosomes are an exception, because males inherit one copy each of the X and the Y chromosome; females inherit two copies of the X chromosome.) In many cases, only one of the two genes is expressed. The gene that is expressed is referred to as the dominant gene; the gene that is not expressed is referred to as the recessive gene.

If the defective gene in EDS is autosomal dominant, an individual who inherits it will develop the symptoms of EDS. If the defective gene is autosomal recessive, the individual will not develop symptoms of EDS, as long as the other gene is normal.

Causes & symptoms

EDS is caused by a defect in one of the genes involved in collagen production. Some types of EDS are known to be related to a genetic flaw because of the observed inherited pattern, but the exact defect may not be identified.

Classification of EDS types was revised in 1997. The new classification is simpler and based more on descriptions of the actual symptoms. EDS is now classified into six major types: classical, hypermobility, vascular, kyphoscoliosis, arthrochalasia, and dermatosparaxis, and a collection of rare or poorly defined varieties.

Classical type

Under the old classification system, EDS classical type was divided into two separate types: type I and type II. The major symptoms involve the skin and joints. The skin has a smooth, velvety texture and bruises easily. Individuals with classical type EDS typically have extensive scarring at pressure points such as the knees, elbows, forehead, and chin. Owing to loose joints, individuals are at substantial risk for slowed motor development, poor muscle tone, sprains, and partial or complete joint dislocations. Children may have a tendency to develop hernias or other organ shifts within the abdomen. EDS classical type is inherited in an autosomal dominant manner.

Hypermobility type

Excessively loose joints are the hallmark of this EDS type, formerly known as EDS type III. Both large joints, such as the elbows and knees, and small joints, such as toes and fingers, are affected. Partial and total joint dislocations are common, and particularly involve the jaw, knee, and shoulder. Many individuals experience chronic limb and joint pain, although x rays are normal. The skin may also bruise easily. EDS hypermobility type is inherited in an autosomal dominant manner.

Vascular type

Formerly called EDS type IV, EDS vascular type carries the risk of premature death. The connective tissue in the intestines, arteries, and uterus is unusually weak, leading to a strong possibility of organ or blood vessel rupture. Such ruptures are more likely between ages 20-40, although they can occur any time, and can be life-threatening. The large joints have normal stability, but small joints in the hands and feet are loose. The skin is thin and translucent, with veins dramatically visible. The skin bruises easily. Other complications can include collapsed lungs, premature aging of the skin on the hands and feet, formation of openings between arteries and veins, and complications following surgery. EDS vascular type is inherited in an autosomal dominant manner.

Kyphoscoliosis type

The major symptoms of kyphoscoliosis type, formerly called EDS type VI, are general joint looseness. At birth, the muscle tone is poor, and motor skill development is delayed. Also, infants with this type of EDS have an abnormal curvature of the spine (scoliosis). The scoliosis becomes progressively worse with age to the point that the individual may no longer be able to walk by age 20. The eye and skin are fragile and easily damaged, and blood vessel involvement is a possibility. The bones may also be affected as demonstrated by a decreased amount of bone tissue. Kyphoscoliosis type is inherited in an autosomal recessive manner.

Arthrochalasia type

Dislocation of the hip joint typically accompanies arthrochalasia type EDS, formerly called EDS type VIIB. Other joints are also unusually loose, leading to recurrent partial and total dislocations. The skin has a high degree of stretchability and bruises easily. Individuals with this type of EDS may also experience mildly diminished bone mass, scoliosis, and poor muscle tone. Arthrochalasia type is inherited in an autosomal dominant manner.

Dermatosparaxis type

Individuals with this type of EDS, once called type VIIC, have extremely fragile skin that bruises easily but does not scar excessively. The skin is soft and may sag, leading to an aged appearance even in young adults. Individuals may also experience hernias. Dermatospraraxis type is inherited in an autosomal recessive manner.

Other types

Certain EDS types have retained their original classifications owing to their rarity and a lack of complete information.

Diagnosis

Symptoms such as extreme joint looseness and unusual skin qualities, as well as family history, can lead to a diagnosis of EDS. Specific tests such as skin biopsies are available for certain types of EDS, including vascular, arthrochalasia, and dermatosparaxis types. A skin biopsy involves removing a small sample of skin and examining its microscopic structure. Urine testing is done for the Kyphoscoliosis type.

Treatment

Medical therapy rests on managing the symptoms and trying to prevent complications; EDS cannot be cured. Braces may be prescribed to stabilize joints, although surgery is sometimes necessary to repair joint damage caused by repeated dislocations. Physical therapy teaches individuals how to strengthen muscles around joints and prevent or limit damage.

Alternative treatment

There are anecdotal reports that large daily doses (1-4 grams) of vitamin C help decrease bruising and aid in wound healing. An individual with EDS should double check this type of therapy with a physician. Therapy that doesn't require medical consultation involves protecting the skin with sun screen and avoiding activities that place stress on the joints. Constitutional homeopathic treatment may be helpful in maintaining optimal health in persons with a diagnosis of EDS.

Prognosis

The outlook for individuals with EDS depends on the type of disorder. Symptoms vary in severity, which alters the frequency of complications on an individual basis. Most individuals will have a normal lifespan, but people with blood vessel involvement, especially EDS vascular type, have an increased risk of fatal complications. Extreme joint instability and scoliosis may limit a person's mobility.

Prevention

Since EDS is a genetic disorder; it cannot be prevented. However, some of the complications of the disorder can be avoided to a certain degree. Prior to having children, individuals with EDS should consult their physicians and a genetic counselor to investigate the risks to themselves and to their potential children.

Key Terms

Autosomal

Refers to genes that are located on chromosomes 1-22. The genes located on the X and Y chromosomes (i.e., the sex chromosomes) are excluded.

Biopsy

A medical test in which a small amount of a tissue is surgically removed and then examined microscopically for evidence of disease or disorder.

Collagen

A type of protein found throughout the body that forms the framework for organs, blood vessels, tendons, cartilage, and many other tissues.

Dominant

Refers to the gene that is expressed when there are two dissimilar genes that code for the same product.

Gene

The expanse of DNA (deoxyribonucleic acid) that encodes the blueprint for a specific product, such as a protein.

Hernia

A medical disorder in which an organ or part of an organ protrudes through the tissues that normally surround it.

Recessive

Refers to the gene that is not expressed when there are two dissimilar genes that code for the same product.

Scoliosis

A medical condition in which the spine has an abnormal curvature.

Further Reading

For Your Information

Books

• Byers, Peter H. "Disorders of Collagen Biosynthesis and Structure." In The Metabolic and Molecular Bases of Inherited Disease. Vol. 3. 7th ed., edited by Charles R. Scriver, et al. New York: McGraw-Hill, Inc., 1995.

  Periodicals

• Beighton, P., et al. "Ehlers-Danlos Syndrome: Revised Nosology, Villefranche, 1997." American Journal of Medical Genetics In press.
• Pope, M. F., and Burrows, N. P., "Ehlers-Danlos Syndrome has Varied Molecular Mechanisms." Journal of Medical Genetics. 34(1997): 400.

  Organizations

• Ehlers-Danlos National Foundation. 6399 Wilshire Blvd., Suite 510, Los Angeles, CA 90048. (213) 651-3038. http://www.ednf.org/.

Gale Encyclopedia of Medicine. Gale Research, 1999.