Editing Arthrogryposis (section)

==Causes==
[[File:Sheldon-Hall syndrome.JPG|thumb|150px|A child with Sheldon–Hall syndrome, a form of arthrogryposis caused by mutations in the MYH3, TNN12, TNNT3 or TPM2 genes]]
Research of arthrogryposis has shown that anything that inhibits normal joint movement before birth can result in joint contractures.<ref name=Bamshad />  Arthrogryposis could be caused by genetic and environmental factors. In principle: any factor that curtails fetal movement can result in congenital contractures.<ref name=Bevan /> The exact causes of arthrogryposis are unknown.

===Extrinsic factors===
The malformations of arthrogryposis can be secondary to environmental factors such as: decreased [[intrauterine]] movement, [[oligohydramnios]] (low volume or abnormal distribution of intrauterine fluid), and defects in the fetal blood supply. Other causes could be: [[hyperthermia]], limb immobilization and viral infections. A specific virus that may cause arthrogryposis is contraction of the [[Zika virus]] during pregnancy. Congenital Zika syndrome (CZS), may occur when there is vertical transmission of the Zika virus to the fetus.<ref>{{Cite book|title=Children with disabilities|publisher=Paul H. Brookes Pub.|year=2019|isbn=978-1681253206|location=Baltimore|pages=31}}</ref> [[Myasthenia gravis]] of the mother leads also in rare cases to arthrogryposis. The major cause in humans is fetal [[akinesia]]; however, this is disputed lately.<ref name=Kalampokas />

===Intrinsic factors===
Arthrogryposis could also be caused by intrinsic factors. This includes molecular, muscle- and [[connective tissue]] development disorders or neurological abnormalities.<ref name=Bamshad/>

===Molecular basis===
Research has shown that there are more than 35 specific genetic disorders associated with arthrogryposis. Most of those [[mutations]] are [[missense]], which means the mutation results in a different [[amino acid]]. Other mutations that could cause arthrogryposis are: single gene defects (X-linked recessive, autosomal recessive and autosomal dominant), [[mitochondrial]] defects and [[chromosomal]] disorders (for example: [[trisomy 18]]).<ref name=Bevan /> This is mostly seen in distal arthrogryposis. Mutations in at least five genes (TNN12, TNNT3, TPM2, MYH3 and MYH8) could cause distal arthrogryposis.<ref name=Bamshad /> There could be also connective tissue, neurological or muscle development disorders.<ref name=Bamshad />

===Muscle and connective tissue development disorders===
Loss of muscle mass with an imbalance of muscle power at the joint can lead to connective tissue abnormality.<ref name=Kalampokas /> This leads to joint fixation and reduced fetal movement.<ref name=Kalampokas /> Also muscle abnormalities could lead to a reduction of fetal movement.
Those could be: [[dystrophy]], [[myopathy]] and [[mitochondrial]] disorders. This is mostly the result of abnormal function of the [[dystrophin]]-[[glycoprotein]]-associated complex in the [[sarcolemma]] of skeletal muscles.<ref name=Kalampokas />

===Neurological abnormalities===
Seventy to eighty percent of cases of the most severe forms of arthrogryposis are caused by neurological abnormalities, which can be either genetic or environmental.<ref name=Bamshad />

The underlying aetiology and pathogenesis of congenital contractures, particularly arthrogryposis and the mechanism of the mutations remains an active area of investigation, because identifying these factors could help to develop treatment and congenital finding of arthrogryposis.<ref name=Bamshad /><ref name=Wynne-Davies>{{cite journal | vauthors = Wynne-Davies R, Williams PF, O'Connor JC | title = The 1960s epidemic of arthrogryposis multiplex congenita: a survey from the United Kingdom, Australia and the United States of America | journal = The Journal of Bone and Joint Surgery. British Volume | volume = 63-B | issue = 1 | pages = 76–82 | date = February 1981 | pmid = 7204479 | doi = 10.1302/0301-620X.63B1.7204479 | doi-access = free }}</ref>