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Ehlers-Danlos syndrome

Reviewed May 2006

What is Ehlers-Danlos syndrome?

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

In the past, there were more than 10 recognized types of Ehlers-Danlos syndrome. In 1997, researchers proposed a simpler classification that reduced the number of major types to six and gave them descriptive names: the arthrochalasia type, the classic type, the dermatosparaxis type, the hypermobility type, the kyphoscoliosis type, and the vascular type. Other forms of the condition may exist, but they have been reported only in single families or are not well characterized.

Although all types of Ehlers-Danlos syndrome affect the joints and many also affect the skin, features vary by type. An unusually large range of joint movement (hypermobility) occurs with most forms of Ehlers-Danlos syndrome, particularly the hypermobility type. Infants with hypermobile joints often appear to have weak muscle tone, which can delay the development of motor skills such as sitting, standing, and walking. The loose joints are unstable and prone to dislocation, chronic pain, and early-onset arthritis. Dislocations involving both hips are a characteristic finding in infants with the arthrochalasia type of Ehlers-Danlos syndrome.

Many people with Ehlers-Danlos syndrome have soft, velvety skin that is highly elastic (stretchy) and fragile. Affected individuals tend to bruise easily, and some types of the condition also cause abnormal scarring. People with the classic form of Ehlers-Danlos syndrome experience wounds that split open with little bleeding and leave scars that widen over time to create characteristic shallow "cigarette paper" scars. The dermatosparaxis type of the disorder is characterized by skin that sags and wrinkles. Extra (redundant) folds of skin may be present as affected children get older.

Some forms of Ehlers-Danlos syndrome, notably the vascular and kyphoscoliosis types, can involve serious and potentially life-threatening complications. Blood vessels can tear (rupture) unpredictably, causing internal bleeding, stroke, and shock. The vascular type of Ehlers-Danlos syndrome is also associated with an increased risk of organ rupture, including tearing of the intestine and rupture of the uterus (womb) during pregnancy. People with the kyphoscoliosis form of Ehlers-Danlos syndrome experience severe, progressive curvature of the spine that can interfere with breathing.

How common is Ehlers-Danlos syndrome?

Although it is difficult to estimate the overall frequency of Ehlers-Danlos syndrome, the combined prevalence of all types of this condition may be about 1 in 5,000 individuals worldwide. The hypermobility and classic forms are most common; the hypermobility type may affect as many as 1 in 10,000 to 15,000 people, while the classic type probably occurs in 1 in 20,000 to 40,000 people.

Other forms of Ehlers-Danlos syndrome are very rare. About 30 cases of the arthrochalasia type and fewer than 60 cases of the kyphoscoliosis type have been reported worldwide. About a dozen infants and children with the dermatosparaxis type have been described. The vascular type is also rare; estimates vary widely, but the condition may affect about 1 in 250,000 people.

What genes are related to Ehlers-Danlos syndrome?

Mutations in the ADAMTS2, COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, PLOD1, and TNXB genes cause Ehlers-Danlos syndrome.

Some of these genes (COL1A1, COL1A2, COL3A1, COL5A1, and COL5A2) provide instructions for making proteins that are used to assemble different types of collagen. Collagens are molecules that give structure and strength to connective tissues throughout the body. Other genes (ADAMTS2, PLOD1, and TNXB) provide instructions for making proteins that process or interact with collagen. Mutations that cause the different forms of Ehlers-Danlos syndrome disrupt the structure, production, or processing of collagen, preventing these molecules from being assembled properly. These defects weaken connective tissues in the skin, bones, and other parts of the body, resulting in the characteristic features of this condition.

Related Gene(s)

Changes in these genes are associated with Ehlers-Danlos syndrome.

  • ADAMTS2
  • COL1A1
  • COL1A2
  • COL3A1
  • COL5A1
  • COL5A2
  • PLOD1
  • TNXB

How do people inherit Ehlers-Danlos syndrome?

The inheritance pattern of Ehlers-Danlos syndrome varies by type. The arthrochalasia, classic, hypermobility, and vascular forms of the disorder usually have an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means that one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new (sporadic) gene mutations. These cases occur in people with no history of the disorder in their family.

The dermatosparaxis and kyphoscoliosis types of Ehlers-Danlos syndrome, and some cases of the classic and hypermobility forms, are inherited in an autosomal recessive pattern. In autosomal recessive inheritance, two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder.

Where can I find information about diagnosis or management of Ehlers-Danlos syndrome?

These resources address the diagnosis or management of Ehlers-Danlos syndrome and may include treatment providers.

  • Gene Review: Ehlers-Danlos Syndrome, Classic Type (http://www.ncbi.nlm.nih.gov/books/NBK1244)
  • Gene Review: Ehlers-Danlos Syndrome, Hypermobility Type (http://www.ncbi.nlm.nih.gov/books/NBK1279)
  • Gene Review: Ehlers-Danlos Syndrome, Kyphoscoliotic Form (http://www.ncbi.nlm.nih.gov/books/NBK1462)
  • Gene Review: Ehlers-Danlos Syndrome Type IV (http://www.ncbi.nlm.nih.gov/books/NBK1494)
  • Genetic Testing Registry: Dermatosparaxis (http://www.ncbi.nlm.nih.gov/gtr/conditions/C2700425)
  • Genetic Testing Registry: Ehlers-Danlos syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0013720)
  • Genetic Testing Registry: Ehlers-Danlos syndrome, hydroxylysine-deficient (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0268342)
  • Genetic Testing Registry: Ehlers-Danlos syndrome, procollagen proteinase deficient (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0268345)
  • Genetic Testing Registry: Ehlers-Danlos syndrome, type 1 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0268335)
  • Genetic Testing Registry: Ehlers-Danlos syndrome, type 2 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0268336)
  • Genetic Testing Registry: Ehlers-Danlos syndrome, type 3 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0268337)
  • Genetic Testing Registry: Ehlers-Danlos syndrome, type 4 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0268338)
  • MedlinePlus Encyclopedia: Ehlers-Danlos Syndrome (http://www.nlm.nih.gov/medlineplus/ency/article/001468.htm)
  • MedlinePlus Encyclopedia: Hyperelastic Skin (http://www.nlm.nih.gov/medlineplus/ency/article/003280.htm)
  • MedlinePlus Encyclopedia: Hypermobile Joints (http://www.nlm.nih.gov/medlineplus/ency/article/003295.htm)

You might also find information on the diagnosis or management of Ehlers-Danlos syndrome in Educational resources (http://www.ghr.nlm.nih.gov/condition/ehlers-danlos-syndrome/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/ehlers-danlos-syndrome/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about Ehlers-Danlos syndrome?

You may find the following resources about Ehlers-Danlos syndrome helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for Ehlers-Danlos syndrome?

  • EDS
  • Ehlers Danlos disease

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about Ehlers-Danlos syndrome?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding Ehlers-Danlos syndrome?

arthritis ; autosomal ; autosomal dominant ; autosomal recessive ; cell ; chronic ; collagen ; deficiency ; dislocation ; elastic ; gene ; hypermobility ; inheritance ; inheritance pattern ; inherited ; intestine ; joint ; kyphoscoliosis ; motor ; muscle tone ; mutation ; pattern of inheritance ; prevalence ; recessive ; rupture ; shock ; sporadic ; syndrome ; vascular

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Beighton P, De Paepe A, Steinmann B, Tsipouras P, Wenstrup RJ. Ehlers-Danlos syndromes: revised nosology, Villefranche, 1997. Ehlers-Danlos National Foundation (USA) and Ehlers-Danlos Support Group (UK). Am J Med Genet. 1998 Apr 28;77(1):31-7. (http://www.ncbi.nlm.nih.gov/pubmed/9557891?dopt=Abstract)
  • Colige A, Sieron AL, Li SW, Schwarze U, Petty E, Wertelecki W, Wilcox W, Krakow D, Cohn DH, Reardon W, Byers PH, Lapière CM, Prockop DJ, Nusgens BV. Human Ehlers-Danlos syndrome type VII C and bovine dermatosparaxis are caused by mutations in the procollagen I N-proteinase gene. Am J Hum Genet. 1999 Aug;65(2):308-17. (http://www.ncbi.nlm.nih.gov/pubmed/10417273?dopt=Abstract)
  • Germain DP. Clinical and genetic features of vascular Ehlers-Danlos syndrome. Ann Vasc Surg. 2002 May;16(3):391-7. Epub 2002 May 21. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12016538?dopt=Abstract)
  • Giunta C, Superti-Furga A, Spranger S, Cole WG, Steinmann B. Ehlers-Danlos syndrome type VII: clinical features and molecular defects. J Bone Joint Surg Am. 1999 Feb;81(2):225-38. Review. (http://www.ncbi.nlm.nih.gov/pubmed/10073586?dopt=Abstract)
  • Nicholls AC, Sher JL, Wright MJ, Oley C, Mueller RF, Pope FM. Clinical phenotypes and molecular characterisation of three patients with Ehlers-Danlos syndrome type VII. J Med Genet. 2000 Nov;37(11):E33. (http://www.ncbi.nlm.nih.gov/pubmed/11073542?dopt=Abstract)
  • Oderich GS, Panneton JM, Bower TC, Lindor NM, Cherry KJ, Noel AA, Kalra M, Sullivan T, Gloviczki P. The spectrum, management and clinical outcome of Ehlers-Danlos syndrome type IV: a 30-year experience. J Vasc Surg. 2005 Jul;42(1):98-106. (http://www.ncbi.nlm.nih.gov/pubmed/16012458?dopt=Abstract)
  • Schalkwijk J, Zweers MC, Steijlen PM, Dean WB, Taylor G, van Vlijmen IM, van Haren B, Miller WL, Bristow J. A recessive form of the Ehlers-Danlos syndrome caused by tenascin-X deficiency. N Engl J Med. 2001 Oct 18;345(16):1167-75. (http://www.ncbi.nlm.nih.gov/pubmed/11642233?dopt=Abstract)
  • Schwarze U, Atkinson M, Hoffman GG, Greenspan DS, Byers PH. Null alleles of the COL5A1 gene of type V collagen are a cause of the classical forms of Ehlers-Danlos syndrome (types I and II). Am J Hum Genet. 2000 Jun;66(6):1757-65. Epub 2000 May 4. (http://www.ncbi.nlm.nih.gov/pubmed/10796876?dopt=Abstract)
  • Uitto J. The Ehlers-Danlos syndrome--phenotypic spectrum and molecular genetics. Eur J Dermatol. 2005 Sep-Oct;15(5):311-2. (http://www.ncbi.nlm.nih.gov/pubmed/16172036?dopt=Abstract)
  • Whitelaw SE. Ehlers-Danlos Syndrome, classical type: case management. Pediatr Nurs. 2003 Nov-Dec;29(6):423-6. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14743836?dopt=Abstract)
  • Yeowell HN, Walker LC. Mutations in the lysyl hydroxylase 1 gene that result in enzyme deficiency and the clinical phenotype of Ehlers-Danlos syndrome type VI. Mol Genet Metab. 2000 Sep-Oct;71(1-2):212-24. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11001813?dopt=Abstract)
  • Zweers MC, Bristow J, Steijlen PM, Dean WB, Hamel BC, Otero M, Kucharekova M, Boezeman JB, Schalkwijk J. Haploinsufficiency of TNXB is associated with hypermobility type of Ehlers-Danlos syndrome. Am J Hum Genet. 2003 Jul;73(1):214-7. (http://www.ncbi.nlm.nih.gov/pubmed/12865992?dopt=Abstract)
  • Zweers MC, van Vlijmen-Willems IM, van Kuppevelt TH, Mecham RP, Steijlen PM, Bristow J, Schalkwijk J. Deficiency of tenascin-X causes abnormalities in dermal elastic fiber morphology. J Invest Dermatol. 2004 Apr;122(4):885-91. (http://www.ncbi.nlm.nih.gov/pubmed/15102077?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: May 2006
Published: December 22, 2014