Ehler-Danlos+Syndrome

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= __ Ehlers Danlos Syndrome __   = By Tom Kenary and Jacob Pagano

__ The Description Of The Disorder __
Ehlers Danlos syndrome refers to a group of inherited genetic disorders that affect the  [|collagen]   and the function it performs;as a result, these disorders most commonly affect the skin, ligaments, joints, and blood vessels. Also, the Ehlers-Danlos syndrome foundation (EDS) has concluded in 1996 that one in 5,000 to 10,000 people are affected by the syndrome due to to the large number of genes that encode for the production of collagen. Ehlers Danlos Syndrome is divided into six sub-types Classical type (I and II), Hypermobility Type, (III) Vascular type (IV) Kyphoscoliosis type(VI), Athroscholasia Type(VII) and Dermatosparaxis type. (VIIC).(1)

A Video Describing Ehlers Danlos syndrome and a situation in which a geneticist uses a pedigree to evaluate a patient with symptoms of EDS. media type="youtube" key="m9rx2n9zw2c" height="295" width="480"Began Video At 1:36-2:19(3)

__ The Pattern Of Inheritance/Genetic Counseling __
Genetic Counseling is used by families to understand the probability of future children inheriting the disease. Those diagnosed with an [|autosomal dominant]form of EDS have a 50% chance of passing the disorder on when the wife/husband is clean to a child in each pregnancy with a. Those diagnosed with autosmal recessive have an extremely low rate(0%) of passing the disease on when mating with someone that has no gene for the syndrome.One can inherit EDS recessive only if both parents have the [|recessive gene.]If A father with an X-linked chromosome that has the syndrome has children with a clean mother, the sons will be unaffected, however both daughters will be carriers. If a mother is a carrier for X linked recessive EDS, she may have affected/unaffected sons, and carrier or unaffected daughters depending on the father.(4)

Sample problem
Suppose an affected female of EDS vascular type mated with a male and half of the offspring were carriers while the other have were clean. What are the possible allele combinations of the male? Is the male affected by EDS? The female Also is Vascular type inherited in the autosomal dominant or recessive manner?

D=Dominant allele for EDS= has EDS d=recessive allele for EDS=free of EDS The child outcome when the male is Dd and the female is dd offspring ratio- 50%-Have condition with alleles Dd. 50%=free of EDS
 * ~  ||   D ||<    d    ||~       ||
 * <   d    ||<    Dd    ||<    dd    ||
 * <   d    ||<    Dd    ||    dd    ||

D=dominant allele for EDS= does not have it d=recessive allele for EDS=has it ||  D  || d ||~   || 50%=carrier of EDS ||~ ||~  ||   **The Cause Of The Disorder-**   Mutations in the    [|ADAMTS2]   ,    [|C0L1A1]    ,    [|COL1A2]    ,    [|COL3A1]    ,    [|COL5A1,]       [|COL5A2]    ,    [|PLODI]    , and    [|TNXB]    genes cause Ehlers Danlos syndrome. Some of these genes, including COL1A1, and COL1A2 ADAMTS2, PLOD1, and TNXB provide instructions for making amino acids that are later used to assemble different types of Collagen. The specific mutation in these genes is not known; however the genes that are involved in causing the syndrome are known. When these genes are mutated, the result is weakened collagen. Ehlers danlos syndrome can directly affect the protiens that are made to assemble the collagen or in                  this case, disrupt           the code for protiens, resulting in mutated proteins that are used to assemble the collagen. As a result, the symptoms are shown.(4)
 * >   d    ||    Dd    ||    dd    ||
 * >   d    ||    Dd    ||    dd    ||~   ||~   ||~   ||
 * ~ offspring ratio=50% have EDS

**The ADAMTS2 Gene-**
  The Gene ADAMTS2 genes scientific name is ADAM metallopeptidase with thrombospondin type 1 motif, 2.”The Normal Function Of The AMAMTS2 gene-provides instructions for making an enzyme that procceses several types of procollagen molecules. Procollagens,- precursors of the collagen which in this case provide support, strength, and the ability to stretch to many body tissues.                 __What is the function of the gene-the enzyme made by the ADAMTS2__ -  the gene clips off a short chain of amino acids off of procollagens. This is necessary in creating collagen molecules that will asssemble into strong slender fibrils that will make up the collagen. Various mutations n the ADAMTS2 gene have been found in people with the EDS Dermatosparaxis type.   People suffer with improperly assembled collagen fibrils, that appear as disroganized under a microscope. The result is weakened        connective tissue, which includes ligaments being easily torn, organs bursting and abnormaly stretching skin.   The gene is located on the (q) arm of the      [|chromosome 5.]      <span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;"> and on the base pair 178, 704, 934  <span style="font-size: 120%; font-family: 'Times New Roman',Times,serif;">   <span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">. <span style="font-family: 'Times New Roman',Times,serif;">   <span style="font-size: 120%; font-family: 'Times New Roman',Times,serif;">   <span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;"> (4) <span style="font-size: 120%; font-family: 'Times New Roman',Times,serif;">         __The Genes Significance-__ The mutation in the gene is a result a many sub-types of EDS including vascular type as well as classical type and the symptoms that result from the mutation are decreased muscle tone, stretchy skin, and organ ruptures.

__Symptoms/Sub-Types and Classification__
The Symptoms Vary depending on which one of the six sub types one has. // __Classical type__ (former nomenclature type 1/2); // Decreased muscle tone, thus one may experience delay in motor milestones. <span style="font-size: 90%; font-family: 'Times New Roman',Times,serif;"><span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">  <span style="font-size: 90%; font-family: 'Times New Roman',Times,serif;"><span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">    <span style="font-size: 13px; font-family: 'Times New Roman',Times,serif;"> <span style="font-size: 90%; font-family: 'Times New Roman',Times,serif;"><span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">      <span style="font-size: 13px; font-family: 'Times New Roman',Times,serif;"> <span style="font-size: 90%; font-family: 'Times New Roman',Times,serif;"><span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;"> Hernias as well as organs shifts within the abdomen also occur frequently, for there is a lack of organ support due to lack of collagen. <span style="font-size: 13px; font-family: 'Times New Roman',Times,serif;"> <span style="font-size: 90%; font-family: 'Times New Roman',Times,serif;"><span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;"> Classical Type is inherited in the autosmal dominant manner and the major diagnostic criteria is skin hyperextensibility, wide scars, and joint hypermobility. Appears in one of 20, 000 to 40,000 people. <span style="font-size: 13px; font-family: 'Times New Roman',Times,serif;"> <span style="font-size: 90%; font-family: 'Times New Roman',Times,serif;"><span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;"> Gene mutation-COLA1, ADAMTS2 <span style="font-size: 13px; font-family: 'Times New Roman',Times,serif;"> <span style="font-size: 90%; font-family: 'Times New Roman',Times,serif;"><span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;"> <span style="font-size: 13px; font-family: 'Times New Roman',Times,serif;"><span style="font-size: 13px; font-family: 'Times New Roman',Times,serif;"> <span style="font-size: 90%; font-family: 'Times New Roman',Times,serif;"><span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;"> <span style="font-size: 13px; font-family: 'Times New Roman',Times,serif;"><span style="font-size: 13px; font-family: 'Times New Roman',Times,serif;"> <span style="font-size: 90%; font-family: 'Times New Roman',Times,serif;"><span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">// __Hypermobility Type__ ( former nomenclature- type 4) // :      <span class="Apple-style-span" style="font-size: 120%; font-family: 'Times New Roman',Times,serif;"><span style="font-size: 13px; font-family: 'Times New Roman',Times,serif;"><span style="font-size: 13px; font-family: 'Times New Roman',Times,serif;"> <span style="font-size: 90%; font-family: 'Times New Roman',Times,serif;"><span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;"> chronic limb and joint pain, dislocations in the knees and jaw. This type is inherited in the autosmal dominant manner and the major diagnostic criteria is soft, smooth, and velvety skin, as well as joint hypermobility. Appears in one of 250,000 people. Gene mutation-unkown <span class="Apple-style-span" style="font-size: 120%; font-family: 'Times New Roman',Times,serif;"><span style="font-size: 13px; font-family: 'Times New Roman',Times,serif;"><span style="font-size: 13px; font-family: 'Times New Roman',Times,serif;"><span style="font-size: 90%; font-family: 'Times New Roman',Times,serif;"><span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">    <span style="font-size: 90%; font-family: 'Times New Roman',Times,serif;"><span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">      <span style="font-size: 13px; font-family: 'Times New Roman',Times,serif;"><span style="font-size: 13px; font-family: 'Times New Roman',Times,serif;"> <span style="font-size: 90%; font-family: 'Times New Roman',Times,serif;"><span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;"> <span style="font-size: 13px; font-family: 'Times New Roman',Times,serif;"><span style="font-size: 13px; font-family: 'Times New Roman',Times,serif;"> <span style="font-size: 90%; font-family: 'Times New Roman',Times,serif;"><span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">// __Vascular type__ (former nomenclature- type 4) // ;      <span style="font-size: 13px; font-family: 'Times New Roman',Times,serif;"><span style="font-size: 13px; font-family: 'Times New Roman',Times,serif;"> <span style="font-size: 90%; font-family: 'Times New Roman',Times,serif;"><span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;"> <span style="font-size: 13px; font-family: 'Times New Roman',Times,serif;"><span style="font-size: 13px; font-family: 'Times New Roman',Times,serif;"> <span style="font-size: 90%; font-family: 'Times New Roman',Times,serif;"><span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;"> Translucent skin, Bulging veins in chest area, Large eyes,Thin pinched nose, Slim body, Large joint are stable however small joints are hyperextensible, Collapsed lungs. Premature aging of the skin during birth. Vascular type is inherited in the Autosmal dominant manner and the diagnosis pertains to the severity of the symptoms.Appears in one of 250,000 people. Gene Mutation-COL3A1, ADAMTS2 <span style="font-size: 13px; font-family: 'Times New Roman',Times,serif;"> <span style="font-size: 90%; font-family: 'Times New Roman',Times,serif;"><span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;"> <span style="font-size: 90%; font-family: 'Times New Roman',Times,serif;"><span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">   <span style="font-size: 90%; font-family: 'Times New Roman',Times,serif;"><span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">       <span style="font-size: 13px; font-family: 'Times New Roman',Times,serif;"> <span style="font-size: 90%; font-family: 'Times New Roman',Times,serif;"><span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;"> <span style="font-size: 13px; font-family: 'Times New Roman',Times,serif;"> <span style="font-size: 90%; font-family: 'Times New Roman',Times,serif;"><span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">// __Kyphoscoliosis Type (__ former nomenclature-type 5) // ;      <span style="font-size: 13px; font-family: 'Times New Roman',Times,serif;"> <span style="font-size: 90%; font-family: 'Times New Roman',Times,serif;"><span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;"> General joint looseness, At birth the muscle tone=poor,Due to muscle tone being poor, infants have scoliosis, an abnormal curviture of the spine resulting in a  n inability to walk as one age increases. Eyes and skin are damaged, Bones may be affected due to lack of bone mass       <span style="font-size: 13px; font-family: 'Times New Roman',Times,serif;"> <span style="font-size: 90%; font-family: 'Times New Roman',Times,serif;"><span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">. Kyphoscoliosis type is inherited in the autosmal recessive manner and the clinical diagnosis is prominently progressive joint looseness as well as fragility. Has only been found in a few people worldwide. Gene mutation-PLOD1 // __Athroch__  __alasia type(__ former nomenclature-type 7) // ; dislocation of the hip joint, general joint looseness, stretchy skin, scoliosis Athrochalasia is inherited in the Autosomal recessive manner and the clinical diagnosis is constrant dislocations. Only 30 cases have been reported worldwide. gene mutation-COL1A1, COL1A2 // __Dermatosparaxis type__ (former nomenclature-type 6) // -Extremely fragile skin that bruises easily;however one with dermatosparaxis type does    not scar.Dermatosparaxis type is inherited in the autosomal recessive manner and the clinical diagnosis is determined by redundant skin sagging and extreme fragility. Only a dozen cases have been found in the world. Gene mutation-ADAMTS2 The new scale contains six sub-types and was created to make the diagnosis processes and treatment decisions easier for patients; however the system has shown to have helped doctors, for more treatments are being developed today.(5)

__Diagnosis__
The diagnosis of Ehlers-Danlos syndrome is based upon the clinical findings of the patient and the family history. For some types of Ehlers-Danlos syndrome, a [|skin biopsy] may be performed to determine the chemical makeup of the connective tissue which can help to diagnose someone. Currently,few types of EDS are able to be diagnosed and these include vascular type, athrascholiosis type, and dermatosparaxis type. One can be diagnosed with these type by means of biochemical laboratory testing or molecular testing. The clinical diagnosis procegure follows the basic criteria. Some types are much easier to identify than others, as demonstrated in the chart below. > >  >  >     (5)
 * skin hyperextensibility
 * joint hypermobility
 * tissue fragility
 * poor wound healing which leads to wide thin scars
 * easy bruising

__**Ehlers Danlos Syndrome In Animals**__
Ehlers-Danlos-syndrome has 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. (10) <span class="Apple-style-span" style="font-family: -webkit-sans-serif; font-size: 18px; line-height: 27px;">

__History/ Evolutionary History of disorder__
The condition was named after the two doctors who first grouped the symptoms. Edvard Ehlers was a Danish physician specializing in dermatology and Henri-Alexandre Danlos was a doctor at the Hospital Tenon, Paris, France. Although it wasn't until 1936 that Frederich Parkes-Weber proposed that the name "Ehlers-Danlos Syndrome" be applied to the disorder the condition was well known before then. A Spanish sailor known as George Albes was infamous for being able to stretch the skin on his chest out to arm's length. He was even asked to attend a meeting of physicians at the Academy of Leyden to demonstrate his unusual ability. Up to 1967 the classification of the Ehlers-Danlos Syndrome only covered those symptoms dealing with fragile skin but by 1986 it had been divided into 11 distinct types covering a wide range of varying symptoms. Later in 1997 these were further simplified into six major types.(5)

<span class="Apple-style-span" style="line-height: 21px; font-size: 14px; font-family: 'Times New Roman',Times,serif;"> __**Advantage to Ehlers Danlos Syndrome**__
Their is no advantage of having this disease.

__Frequency In Certain Groups__
1 in every 5,000 to 10,000 babies born in the U.S. are affected by Ehlers-Danlos syndrome. Reduced life expectancy tends not to be frequent in people with EDS however a recent study that conluded in  2000 of 419 men and women diagnosed with EDS demonstrates that those with type(IV) Vascular type have a median lifespan of 48 years old.Ehlers-Danlos syndrome equally affect all races and are heritable disorders, so even though symptoms may not be seen untill later life, the disorder is present in the person at birth. (4)

__Treatment__
Ehlers-Danlos syndrome is treated according to what particular manifestations are present in a given individual.Skin protection (from injury of trauma and sun, etc.) is critical. Wounds must be tended to with great care and infections must be prevented to promptly treaed. Suturing can be difficult as the skin can be extremely fragile.Joint injury must be avoided. Occasionally, bracing may be necessary to maintain joint stability. Exercises that strengthen the muscles that support the joints can help to minimize joint injury. Contact sports and activities involving joint impact should be avoided.(5)

__ Prognosis __
Due to their not being treatments, it is hard to identify the course of the disease. Researchers have found the vascular type takes a hidden course. Also symptoms such as skin sagging, scaring, and bruising can become progressively worse as one endures more scars and obtains more sun. Joint dislocations can also decrease in number as the person builds muscle to hold them in place;however without this building of muscle EDS can take a course that leads to permanent dislocations. (12)

__**Curability Or Death**__
People with the vascular type of Ehlers-Danlos syndrome have a high risk of sudden death, while other types are manageable.(5)

__New Research__
Today medical researchers are attempting to understand and analyzing the makeup of connective tissue and the specific gene mutations. The Researchers, once they find the gene mutation, hope to apply other recent findings in gene therapy and ultimately cure or prevent the disorder.-The Ehlers Danlos Syndrome National Foundation (EDNF) Announces a new study on Vascular Type EDS. Students from Washington University have begun a study on Jan 1, 2009 with the goal of obtaing the blocks of arterial tissue and the want to understand why people with EDS have fragile arterries. The team has used the information that the mutations of the type 3 collagen are the mutations that trigger the disease. They used this information to obtain new information pertaining to the specific abnormalities of the arterial tissue. So far, they have obtained evidence that those with [|Marfan syndrome] might have a similar disorder in their arterial tissue. This new evidence could be used to alter the risk of arterial bursts or diseases, for the specific defect would be know. (14)

__Effects Of EDS__
Ehlers Danlos syndrome effects people's lives in a large number of ways which include the inability to climb stairs due to joint dislocations. This could possibly affect the job of one with EDS, for their opportnities are limiting. The inability to be exposed to intensive UV light also puts a damper on the lives of people with EDS, for they have to ensure a limited amount of sun obtainment as possible, or their skin will sag to an extreme. Although a child can go to regular school with EDS, the child can not participate in sports and must understand the following to ensure the protection of his joints, skin, and organs. 1. Avoiding sports 2. Avoiding stairs as well as other recreation fun  3. Understanding how to bring joints back to proper position( a painful procedure)  4. Must strengthen joints at physical therapy  5. Must receive periodic checkups at the doctor Peoples lives can also be challenged in their homes, and in some scenarios people might have to buy a electric scooter that attaches to a specially designed railing on their stairs in order for them to get up. Also, one with the Vascular type needs to have frequent eye checks, for the mutation in vascular type can trigger another mutation that reduces ones vision and harms the eyes. (16)  Video Demonstrating the hardships that one endures daily due to EDS and how the disease affects their everyday lives in society. media type="youtube" key="PunQu-bId1M" height="344" width="425" watch video from 0:00-0:45(17)

Discussion Question
After watching the second video on The Ehlers Danlos Syndrome Page (from 0;00 to 00;47 seconds), In what way do you think EDS will affect Cameron growing up in his everyday life of school and activities?

__Key Terms-__
**<span style="font-family: 'Times New Roman',Times,serif;"> <span style="font-family: 'Times New Roman',Times,serif;">Syndrome- <span style="font-family: 'Times New Roman',Times,serif;">a group of symptoms that consistently occur together of a condition   **  <span style="font-family: 'Times New Roman',Times,serif;"> **<span style="font-family: 'Times New Roman',Times,serif;"> <span style="font-family: 'Times New Roman',Times,serif;">characterized by a set of associated symptoms <span style="font-family: 'Times New Roman',Times,serif;"> Collagen- <span style="font-family: 'Times New Roman',Times,serif;">the main structural protein found in animal connective tissue, yielding gelatin when boiled. ** <span style="font-family: 'Times New Roman',Times,serif;"><span style="font-family: 'Times New Roman',Times,serif;"> <span style="font-family: 'Times New Roman',Times,serif;"> **<span style="font-family: 'Times New Roman',Times,serif;"><span style="font-family: 'Times New Roman',Times,serif;">Marfan syndrome- ** <span style="font-family: 'Times New Roman',Times,serif;"><span style="font-family: 'Times New Roman',Times,serif;">Marfan syndrome (or Marfan's syndrome) is a genetic disorder of the  <span style="font-family: 'Times New Roman',Times,serif;">[|**connective tissue**] **<span style="font-family: 'Times New Roman',Times,serif;"> <span style="font-family: 'Times New Roman',Times,serif;">. <span style="font-family: 'Times New Roman',Times,serif;"> ** **<span style="font-family: 'Times New Roman',Times,serif;">Hyperextensibility **<span style="font-family: 'Times New Roman',Times,serif;">-The ability to extend a joint beyond the normal range <span style="font-family: 'Times New Roman',Times,serif;">  <span style="font-family: 'Times New Roman',Times,serif;">  <span style="font-family: 'Times New Roman',Times,serif;"> **<span style="font-family: 'Times New Roman',Times,serif;">Hypermobility <span style="font-family: 'Times New Roman',Times,serif;">- **<span style="font-family: 'Times New Roman',Times,serif;">Unusual flexibilty of joints, allowing them to be bent beyond their normal range of motion. <span style="font-family: 'Times New Roman',Times,serif;"> **<span style="font-family: 'Times New Roman',Times,serif;">Joint Dislocation **<span style="font-family: 'Times New Roman',Times,serif;">-The displacement of a bone. **<span style="font-family: 'Times New Roman',Times,serif;">Carrier **<span style="font-family: 'Times New Roman',Times,serif;">=a person or other organism that possesses a particular gene, esp. as a single copy whose effect is masked by a dominant allele, so that the associated characteristic (such as a hereditary disease) is not displayed but may be passed to offspring. <span style="font-family: 'Times New Roman',Times,serif;">**Sporadic**-occurring only in a few places. <span style="font-size: 13px; font-family: 'Times New Roman',Times,serif;"> <span style="font-size: 90%; font-family: 'Times New Roman',Times,serif;"><span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;"> <span style="font-family: 'Times New Roman',Times,serif;">**Hernia**-       <span style="font-size: 13px; font-family: 'Times New Roman',Times,serif;"> <span style="font-size: 90%; font-family: 'Times New Roman',Times,serif;"><span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;"> <span style="font-family: 'Times New Roman',Times,serif;">A rupture in the wall of a body cavity, through which an organ may protrude. <span style="font-family: 'Times New Roman',Times,serif;">

Web Site __Web link__ (1)"Ehlers Danlos syndrome." emedicene.com. 9 Jan. 2009. 9 Jan. 2009 <__http://emedicine.medscape.com/article/1114004-overview__>. __New EditCopy Delete Parenthetical Reference Have a Question?
 * References**

__Web Site__ Web link __(2)courses.cm.utexas__ . 18 May 2007. 9 Jan. 2009 <__http://courses.cm.utexas.edu/__________ <span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 15px; line-height: normal; font-size-adjust: none; font-stretch: normal;">jrobertus/ch339k/overheads-1/ch6_collagen.jpg>. EditCopy Delete    __ Parenthetical Reference __ Have a Question? __

__Web Site__ Web link __(3)"Ehlers Danlos:A Mystery." www.youtube.com. 5 Jan. 2009. 9 Jan. 2009 <__http://www.youtube.com/watch?v=m9rx2n9zw2c__>. 0 __New__ __EditCopy____Delete__ __Parenthetical Reference__ __Have a Question?__

web Site __Web link__ (4)"Ehlers Danlos Syndrome." www.ghr.nlm.nih.gov. 6 May 2006. 8 Jan. 2009 <__http://ghr.nlm.nih.gov/condition=ehlersdanlossyndrome______________________>. <span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 15px; line-height: normal; font-size-adjust: none; font-stretch: normal;">0 <span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 15px; line-height: normal;"> __New<span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 15px; line-height: normal; font-size-adjust: none; font-stretch: normal;"> EditCopyDelete Parenthetical Reference Have a Question?__

Web Site __Web link__ (5)"Ehlers Danlos Syndrome(treated)." www.medicenet.com. 1 Jan. 2009. 9 Jan. 2009 <__http://www.medicinenet.com/ehlers-danlos_syndrome/article.htm__>. <span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 15px; line-height: normal; font-size-adjust: none; font-stretch: normal;">0 <span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 15px; line-height: normal;"> __New EditCopy Delete Parenthetical Reference Have a Question?

__Web Site__ Web link __(6)"skin biopsy." content.answers.com. 9 Apr. 2006. Yale University. 9 Jan. 2009__ new EditCopy Delete Parenthetical Reference Have a Question? __<__http://images.google.com/imgres?imgurl=http://content.answers.com/main/__ content/img/medTest/f017002.jpg&imgrefurl= __http://www.answers.com/topic/__ <span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 15px; line-height: normal; font-size-adjust: none; font-stretch: normal;">skin-biopsy&usg= IkHAIaii9P9-yhEJqDmUN9QCKtg=&h=546&w=650&sz=36&hl=en&start=3&u<span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 15px; line-height: normal; font-size-adjust: none; font-stretch: normal;">1&tbnid P5F_ulViKaM96M:&tbnh=115&tbnw=137&prev=/ images%3Fq%3Dskin%2Bbiopsy%26um%3D1%26hl%3Den%26client%3Dsafari%26rls%3Den-us%26s a%3DN>.

Web Site__ Web link __(7)"Animal model of human disease: Ehlers Danlos Syndrome."__ www.pubmedcentral.nih.gov__. 2 May 1975. 8 Jan. 2009 <__http://www.pubmedcentral.nih.gov/pagerehttp://__ watch?v=PunQu-bId1Mnder.fcgi?artid=1913024&pageindex=2>. <span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 15px; line-height: normal; font-size-adjust: none; font-stretch: normal;">0 <span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 15px; line-height: normal;"> __New<span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 15px; line-height: normal; font-size-adjust: none; font-stretch: normal;"> Edit<span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 15px; line-height: normal;"> Copy<span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 15px; line-height: normal;"> Delete__ Parenthetical Reference __Have a Question?__

Web Site __Web link__ (8)"hip brace." alimed.com. 11 Dec. 2006. 9 Jan. 2009 < __http://www.alimed.com/____ resources/common/images/products/full/62975_d.jpg>. 0 __New EditCopy Delete Parenthetical Reference Have a Question?

__Web Site__ Web link __(9)"ehlers Danlos syndrome." content.nejm.org. 15 May 2008. 4 Jan. 2009 <__http://content.nejm.org/content/vol357/issue11/images/large/11f1.jpeg__>. <span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 15px; line-height: normal; font-size-adjust: none; font-stretch: normal;">0 <span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 15px; line-height: normal;"> __New<span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 15px; line-height: normal; font-size-adjust: none; font-stretch: normal;"> Edit<span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 15px; line-height: normal;"> Copy<span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 15px; line-height: normal;"> Delete Parenthetical Reference Have a Question?__

Web Site __Web link__ (10)"Hip Dislocation." www.nlm.nih.gov. 10 Jan. 2009. 9 Jan. 2009 <__http://www.nlm.nih.gov/medlineplus/ency/images/ency/fullsize/19098.jpg__>. <span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 15px; line-height: normal;"> __New<span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 15px; line-height: normal; font-size-adjust: none; font-stretch: normal;"> EditCopy Delete Parenthetical Reference Have a Question?

__Web Site__ Web link __(11)"Aneurysm."__ daviddarling.info__. 6 Sept. 2008. 9 Jan. 2009 <__http:////www.daviddarling.info/images/aneurysms.jpg__>. <span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 15px; line-height: normal; font-size-adjust: none; font-stretch: normal;">0 <span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 15px; line-height: normal;"> __New<span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 15px; line-height: normal; font-size-adjust: none; font-stretch: normal;"> Edit<span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 15px; line-height: normal;"> Copy<span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 15px; line-height: normal;"> Delete Parenthetical Reference Have a Question?__

Web Site __Web link__ (12)Mayo Clinic. "Ehlers danlos Syndrome Definition." www.mayoclinic.com. 20 June 2008. 10 Jan. 2009 <__http://www.mayoclinic.com/health/__ ehlers-danlos-syndrome/DS00706>.

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__Web Site__ Web link __(13)"Eds skin." www.healiohealth.com. 1 Apr. 2006. 9 Jan. 2009 <__http://www.healiohealth.com/library/images/ehlers12.jpg__>. __New<span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 13px; line-height: normal;"> Edit <span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 13px; line-height: normal;"> Copy <span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 13px; line-height: normal;"> Delete Parenthetical Reference Have a Question?__

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__Web Site__ Web link (15)content.answers.com__. 8 Sept. 2008. 9 Jan. 2009 <__ http://images.google.com/______ imgres?imgurl= __http://content.answers.com/main/content/img/McGrawHill/__Encyclopedia/images/CE157300FG0010.gif&imgrefurl=__ http://www.answers.com/topic/______connectitissue&usg=__7CQlACYHrfvQcSgcDfgGkPMWb9Q=&h=301&w=299&sz=34&hl=en&star__t=5&um=1&tbnid=dj99HhBkQFVaEM:&tbnh=116&tbnw=115&prev=/images%3Fq%3Dconnective%2Btissue%26um%3D1%26hl%3Den%26client%3Dsafari%26rls%3Denus%26sa%3DN>. <span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 15px; line-height: normal; font-size-adjust: none; font-stretch: normal;">0 <span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 15px; line-height: normal;"> __New<span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 15px; line-height: normal; font-size-adjust: none; font-stretch: normal;"> Edit<span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 15px; line-height: normal;"> Copy<span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 15px; line-height: normal;"> Delete Parenthetical Reference__

Web Site __Web link__ (16)"Ehlers Danlos Syndrome." www.nlm.nih.gov. 28 Sept. 2008. 10 Jan. 2009 <__http://www.nlm.nih.gov/medlineplus/ehlersdanlossyndrome.html__>. <span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 15px; line-height: normal; font-size-adjust: none; font-stretch: normal;">0 <span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 15px; line-height: normal;"> __New<span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 15px; line-height: normal; font-size-adjust: none; font-stretch: normal;"> Edit<span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 15px; line-height: normal;"> Copy<span style="font-family: Arial; font-style: normal; font-variant: normal; font-weight: normal; font-size: 15px; line-height: normal;"> Delete Parenthetical Reference Have a Question?

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