Editing Ehlers–Danlos syndrome (section)

== Causes ==
[[File:JCI0112881.f2.jpg|thumb|The collagen fibril and EDS: (a) Normal collagen fibrils are of uniform size and spacing. Fibrils from a person with dermatosparaxis (b) show dramatic alterations in fibril morphology with severe effects on the tensile strength of connective tissues. A person with classical EDS (c) shows composite fibrils. Fibrils from a TNX-deficient person (d) are uniform in size and no composite fibrils are seen. TNX-null (e) fibrils are less densely packed and not as well aligned to neighboring fibrils.]]
Every type of EDS except the hypermobile type (which affects the vast majority of people with EDS) can be positively tied to specific genetic variation{{citation needed|date=June 2022}}.

[[Mutation|Variation]]s in these genes can cause EDS:<ref name="Malfait_2017" />
* [[Collagen]] primary structure and collagen processing: ''[[ADAMTS2]]'', ''[[Collagen, type I, alpha 1|COL1A1]]'', ''[[Collagen, type I, alpha 2|COL1A2]]'', ''[[Collagen, type III, alpha 1|COL3A1]]'', ''[[Collagen, type V, alpha 1|COL5A1]]'', ''[[Collagen, type V, alpha 2|COL5A2]]''
* Collagen folding and collagen cross-linking: ''[[PLOD1]]'', ''[[FKBP14]]''
* Structure and function of [[myomatrix]]: ''[[Tenascin X|TNXB]]'', ''[[Collagen, type XII, alpha 1|COL12A1]]''
* [[Glycosaminoglycan]] [[biosynthesis]]: ''[[B4GALT7]]'', ''[[B3GALT6]]'', ''[[CHST14]]'', ''[[DSE (gene)|DSE]]''
* [[Classical complement pathway|Complement pathway]]: ''[[Complement component 1r|C1R]]'', ''[[Complement component 1s|C1S]]''
* Intracellular processes: ''[[SLC39A13]]'', ''[[ZNF469]]'', ''[[PRDM5]]''

Variations 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. A defect in collagen can weaken connective tissue in the skin, bones, blood vessels, and organs, resulting in the features of the disorder.<ref name="NIHGHR2016"/> Inheritance patterns depend on the specific syndrome.

Most forms of EDS 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 a disorder. A few are inherited in an autosomal recessive pattern, which means both copies of the gene must be altered for a person to be affected. It can also be an individual (''de novo'' or "sporadic") [[mutation|variation]]. Sporadic variations occur without any inheritance.<ref>{{Cite news|url=https://ehlers-danlos.com/eds-types/|title=EDS Types |work=The Ehlers Danlos Society|access-date=2017-05-22|archive-url=https://web.archive.org/web/20170624041438/https://ehlers-danlos.com/eds-types/|archive-date=2017-06-24|url-status=live}}</ref><!-- Refer to the summary for each Ehlers–Danlos syndrome for a discussion of its inheritance pattern. -->