Ehlers-Danlos syndrome

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Ehlers-Danlos syndrome
Classifications and external resources
ICD-10 Q79.6
ICD-9 756.83
OMIM 130000 130010 130020 130050 305200 225400 229200 130060 225410 130080 225310
MedlinePlus 001468
eMedicine derm/696  ped/654
MeSH C17.300.200.310

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

[edit] Symptoms

Common symptoms are unstable, flexible joints 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. "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 (Mendelian Inheritance in Man (OMIM) 147900). Other symptoms can include eye problems and nearsightedness. Bone deformities such as pectus excavatum (sunken chest) or scoliosis may present early. Most serious are 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]

[edit] 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:

  • Hypermobility, formerly known as EDS type 3, 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, and it can only be identified by examination of a sample of skin collagen. Symptoms can include easy bruising, velvety-smooth skin, mildy hyperextensible skin, and loose, unstable joints. Joint dislocations 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. (Mendelian Inheritance in Man (OMIM) 130020)
  • Classical EDS, formerly known as 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. (Mendelian Inheritance in Man (OMIM) 130000 and Mendelian Inheritance in Man (OMIM) 130010)
  • Vascular EDS, formerly known as 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. Distinctive facial features are associated with this variant; protruding eyes, small chin, thin nose and lips, and sunken cheeks. Pregnancy can be life-threatening in this variant as well. (Mendelian Inheritance in Man (OMIM) 130050)
  • Kyphoscoliosis, formerly known as EDS 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. (Mendelian Inheritance in Man (OMIM) 225400 and Mendelian Inheritance in Man (OMIM) 229200)
  • Arthrochalasis, formerly known as EDS 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. (Mendelian Inheritance in Man (OMIM) 130060)
  • Dermatosparaxis, formerly known as EDS type 7C, is also very rare, with about 10 cases reported. This variant combines the loose and unstable joints with extremely fragile skin which loses elasticity. (Mendelian Inheritance in Man (OMIM) 225410)

"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:

[edit] 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.

[edit] 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.

[edit] EDS-like symptoms in animals

Hyperextensible skin in a dog with EDS
Enlarge
Hyperextensible skin in a dog with EDS

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.

[edit] References

  1. ^ Lawrence EJ (2005). "The clinical presentation of Ehlers-Danlos syndrome". Adv Neonatal Care 5 (6): 301-14. PMID 16338669.
  2. ^ Nicolò Paganini (1782-1840). Retrieved on 2006-10-18.
  3. ^ Beighton P, De Paepe A, Steinmann B, Tsipouras P, Wenstrup RJ (1998). "Ehlers-Danlos syndromes: revised nosology, Villefranche, 1997. Ehlers-Danlos National Foundation (USA) and Ehlers-Danlos Support Group (UK)". Am J Med Genet 77 (1): 31-7. PMID 9557891.

[edit] External links

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