EHLERS-DANLOS SYNDROME

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

Contents

Symptoms

Classification

Genetics

Epidemiology

EDS-like symptoms in animals

See also

References

External links

Symptoms

Common symptoms are unstable, flexible joints (hypermobility) with a tendency to dislocate and subluxate, due to ligaments which are overly stretchable, and elastic, fragile, soft skin that easily forms welts and scars. For many patients with Ehlers-Danlos syndrome, intense pain where the joints dislocate is very common "It was the recommendation of a workshop convened in Berlin by Beighton (1986) that the Ehlers-Danlos designation be used for joint hypermobility with skin changes" [1] in contrast to hypermobility syndromes without skin changes, once known as EDS type 11 (). Other symptoms can include eye problems, such as lens dislocation and myopia. Bone deformities such as pectus excavatum (sunken chest) or scoliosis may present early. Most serious consequences are due to vascular and organ fragility, which are less frequent.^[1] A famous example of one who most likely had this disorder would be Niccolò Paganini.^[2]
It is also rumored that Houdini had a type of Ehlers Danlos, which allowed him to easily dislocate his shoulders to slip out of strait-jackets.

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.^[3] 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:

'Name'	'Number'	'Description'	'OMIM'	'Gene(s)'
Hypermobility	type 3	Affects 1 in 10,000 to 15,000 and is caused by an autosomal dominant mechanism. Mutations in either of two separate genes (which are also involved in 'Vascular EDS' and Tenascin-X deficiency EDS, respectively) may lead to this variant; it is the only type of EDS that ''cannot'' be diagnosed through skin / tissue samples but is rather diagnosed through use of clinical observations. Symptoms can include easy bruising, velvety-smooth skin, mildy hyperextensible skin, and loose, unstable joints. Joint dislocations and subluxations are common. Degenerative joint disease can occur; the pain associated with this condition is a serious complication. Unfortunately, pain medications are frequently underprescribed. Some individuals have mitral valve prolapse, which creates an increased risk for infective endocarditis during surgery, particularly dental surgery, as well as possibly progressing to a life-threatening degree of severity.		,
Classical	types 1 and 2	Affects approximately 2 to 5 in 100,000 people. In addition to the joint and cardiac effects noted above for hypermobility, this variant is characterized by soft, highly elastic, velvety skin which may tear, bruise, or scar easily and/or be slow to heal, and which has a tendency to develop benign fatty growths as well as benign fibrous growths on pressure areas. Pregnancy can be life-threatening in this variant. It affects type-V collagen, as well as type I.	,	, ,
Vascular	type 4	Is an autosomal dominant defect in the type 3 collagen synthesis; affecting approximately 1 in 100,000 people, it is clinically serious, reducing life expectancy to around 40 years. Joint symptoms are usually limited to the fingers or toes, but the delicate skin noted above is joined by fragile blood vessel walls and organ membranes, with a tendency to rupture or develop aneurysms. Thin, translucent skin, Arterial/intestinal/uterine fragility or rupture, Extensive bruising, Characteristic facial appearance - Distinctive facial features are associated with this variant; large eyes, small chin, thin nose and lips, and may also have lobeless (attached) ears, midline (betwen the eyes) facial flattening. Along with the above characteristics, ' a majority have reported that they sleep with their eyes half (partially) open.' Pregnancy can be life-threatening in this variant as well.
Kyphoscoliosis	type 6	Is an autosomal recessive defect due to deficiency of an enzyme called lysyl hydroxylase; it is very rare, with fewer than 60 cases reported. Symptoms include progressive scoliosis, progressive severe weakness of muscles, and fragile sclera.	,
Arthrochalasis	types 7A and 7B	Is also very rare, with about 30 cases reported. This variant may result in very loose and unstable joints, including the hips, which may lead to early and/or severe osteoarthritis and fractures, and stretchy, fragile skin. It affects type-I collagen.		,
Dermatosparaxis	type 7C	Also very rare, with about 10 cases reported. This variant combines the loose and unstable joints with extremely fragile skin which loses elasticity.

It is very important to note that while the above syptomatmology 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." [2] 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 -

★ -- Due to Tenascin-X deficiency -

★ -- Type unspecified

Genetics

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

The overall prevalence of all types of Ehlers-Danlos syndrome may be about 1 in 5,000 births worldwide. The prevalence of the six types differs dramatically. The most common are the hypermobile forms (the classical and hypermobility types). Other forms are very rare. For example, fewer than 10 infants and children with the dermatosparaxis type have been described worldwide. It affects both males and females of all racial and ethnic backgrounds.

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.

See also

★ Gorlin sign

References

1. The clinical presentation of Ehlers-Danlos syndrome, Lawrence EJ, , , Adv Neonatal Care, 2005
2.
3. Ehlers-Danlos syndromes: revised nosology, Villefranche, 1997. Ehlers-Danlos National Foundation (USA) and Ehlers-Danlos Support Group (UK), Beighton P, De Paepe A, Steinmann B, Tsipouras P, Wenstrup RJ, , , Am J Med Genet, 1998

External links

★ EDS Today - The Newsletter for, by, and about people with Ehlers Danlos Syndrome (EDS)

★ Ehlers-Danlos Network C.A.R.E.S. INC - Children, Adults, Research, Education, Support

★ Ehlers-Danlos Support Group

★ Ehlers-Danlos National Foundation

★ Ehlers Danlos Foundation Of New Zealand

★

★ Joint & Bone - Ehlers-Danlos/Joint Hypermobility Syndrome - Proprioception

★ NIH/Medline