Ehlers-Danlos syndrome

Infobox Disease | Name = Ehlers-Danlos syndrome | ICD10 = ICD10|Q|79|6|q|65 | ICD9 = ICD9|756.83 | OMIM = |
MedlinePlus = 001468
eMedicineSubj = derm
eMedicineTopic = 696
eMedicine_mult = eMedicine2|ped|654 | MeshID = D004535

Ehlers-Danlos syndrome is a group of rare genetic disorders affecting humans caused by a defect in collagen synthesis. Depending on the individual mutation, the severity of the syndrome can vary from mild to life-threatening. There is no known cure. Treatment is supportive.

The syndrome is named after two doctors, Edward Ehlers of Denmark, and Henri-Alexandre Danlos of France, who identified it at the turn of the 20th century. ["Uncovered: How U.S. Health System Can Fail Even the Insured --- A Woman Endures 16-Month Odyssey To Get a Diagnosis", John Carreyrou, "Wall Street Journal", November 16, 2007]

ymptoms

Symptoms vary widely based on which type of Ehlers Danlos Syndrome (EDS) the patient has. In each case, however, the symptoms are ultimately due to faulty or reduced amounts of collagen. For example, in the most common type of EDS, Hypermobility Type, symptoms often include unstable, flexible joints with a painful tendency to dislocate and subluxate. This is due to ligaments which, because they are lacking proper collagen--the molecule that provides strength to ligaments--are overly stretchable. The so-called Classic EDS Type features skin that forms cigarette-paper-like scars. Another type of collagen is usually responsible for lending strength to skin (and scars). One of the rarest, and the most serious type of EDS, Vascular EDS, can result in premature death via vascular (blood vessel) and organ rupture. [cite journal | author=Lawrence EJ | title=The clinical presentation of Ehlers-Danlos syndrome | journal=Adv Neonatal Care | year=2005 | pages=301–14 | volume=5 | issue=6 | pmid=16338669 | doi=10.1016/j.adnc.2005.09.006] Again, another type of collagen is necessary to give strength to the walls of blood vessels and the walls of hollow organs (such as the large bowel, aka colon). See table below for a more extensive list of symptoms for each type of EDS. There is some cross-over or similarity of symptoms among the various types. For example, many of the types feature velvety or hyperextensible skin. In addition, persons with Hypermobility Type often have very stretchy ligaments (leading to frequent subluxations/dislocations) while those with Vascular Type have ligaments that rupture. Because it is often undiagnosed, some instances of Ehlers-Danlos syndrome have been mischaracterized as child abuse. [http://www.pe.com/localnews/inland/stories/PE_News_Local_D_abuse03.3d48364.html]

Classification

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. [cite journal | author=Beighton P, De Paepe A, Steinmann B, Tsipouras P, Wenstrup RJ | title=Ehlers-Danlos syndromes: revised nosology, Villefranche, 1997. Ehlers-Danlos National Foundation (USA) and Ehlers-Danlos Support Group (UK) | journal=Am J Med Genet | year=1998 | pages=31–7 | volume=77 | issue=1 | pmid=9557891 | doi=10.1002/(SICI)1096-8628(19980428)77:1<31::AID-AJMG8>3.0.CO;2-O | doi_brokendate=2008-06-26] These six major types are listed below. Other types of the condition may exist, but they have been reported only in single families or are not well characterized. Except for hypermobility, the specific mutations involved have been identified and they can be precisely identified by genetic testing; this is valuable due to a great deal of variation in individual presentation of symptoms which may confuse classification of individuals on purely symptomatic basis. In order of prevalence in the population, they are:

While the above symptomatology is clean and defined the disease itself rarely obeys these neat categorizations. Cross-over symptoms for all types are prevalent and lead to under-diagnosis or mis-diagnosis. No patient should assume or rely on the "fact" they have a certain type of EDS when cross-over symptoms are evident and can be life-threatening.

"The large number of distinct types of the Ehlers-Danlos syndrome that have already been identified indicates great heterogeneity, but clearly that heterogeneity is not exhausted by the present classification." [http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=130090] Examples of types of related syndromes other than those above reported in the medical literature include:
* -- Type 5
* -- Type 8 - unspecified gene, locus 12p13
* -- Type 10 - unspecified gene, locus 2q34
* -- Beasley-Cohen type
* -- Progeroid form - Gene|B4GALT7
* -- Due to Tenascin-X deficiency - Gene|TNXB
* -- Type unspecified

Genetics

Mutations in the following can cause Ehlers-Danlos syndrome:
* Fibrous proteins: COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, and TNXB
* Enzymes: ADAMTS2, PLOD1

Mutations in these genes usually alter the structure, production, or processing of collagen or proteins that interact with collagen. Collagen provides structure and strength to connective tissue throughout the body. A defect in collagen can weaken connective tissue in the skin, bones, blood vessels, and organs, resulting in the features of the disorder.

Inheritance patterns depend on the type of Ehlers-Danlos syndrome. Most forms of the condition are inherited in an autosomal dominant pattern, which means only one of the two copies of the gene in question must be altered to cause the disorder. The minority are inherited in an autosomal recessive pattern, which means both copies of the gene must be altered for a person to be affected by the condition. Please refer to the summary for each type of Ehlers-Danlos syndrome for a discussion of its inheritance pattern.

Epidemiology

Ehlers-Danlos Syndrome is an inherited disorder estimated to occur in about 1 in 5000 births worldwide. Ehlers Danlos affects both males and females of all racial and ethnic backgrounds. Initially, prevalence estimates has previously ranged from 1 in 250,000 to 1 in 500,000 people, but these estimates were soon found to be vastly inaccurate as the disorder received further study and medical professionals became more adept at accurately diagnosing EDS. The prevalence of the six types differs dramatically. The most commonly occurring type is the hypermobility type, followed by the classical type. The other types of EDS are very rare. For example, fewer than 10 infants and children with the dermatosparaxis type have been described worldwide.

EDS-like symptoms in animals

Ehlers-Danlos-like syndromes have been shown to be hereditary in Himalayan cats, some domestic shorthair cats and in certain breeds of cattle. It is seen as a sporadic condition in domestic dogs.

ee also

* Gorlin sign
* Postural orthostatic tachycardia syndrome
* Dural ectasia
* Arnold-Chiari malformation

References

External links

* [http://www.ednf.org Ehlers-Danlos National Foundation]
* [http://www.orthop.washington.edu/uw/ehlersdanlos/tabID__3376/ItemID__32/PageID__1/Articles/Default.aspx University of Washington Medicine, Orthopaedic Surgery and Sports Medicine: Multi-page explanation of the disease, its symptoms, how to cope, etc.]
* [http://www.edstoday.org/ EDS Today - The Newsletter for, by, and about people with Ehlers Danlos Syndrome (EDS)]
* [http://www.ehlersdanlosnetwork.org/Home.asp Ehlers-Danlos Network C.A.R.E.S. INC - Children, Adults, Research, Education, Support]
* [http://www.ehlers-danlos.org/ Ehlers-Danlos Support Group]
* [http://www.edfnz.org.nz/ Ehlers Danlos Foundation Of New Zealand]
*
* [http://www.reumatologia-dr-bravo.cl/para%20medicos/HIPERLAXITUD/www_jointandbone_org_RODGRAH.htm Joint & Bone - Ehlers-Danlos/Joint Hypermobility Syndrome - Proprioception]
* [http://www.nlm.nih.gov/medlineplus/ehlersdanlossyndrome.html NIH/Medline]