The pathophysiology is related to the specific type of arthrogryposis. Exact mechanisms are not well understood in some subtypes of arthrogryposis. In general, fetal akinesia leads to collagen overgrowth, where extra connective tissue forms around the joint leading to the thickening of joint capsules. As movement is restricted, tendons become less pliable, bones become flattened, and there may be decreased limb growth, further increasing the contracture.
In distal arthrogryposis, genetic anomalies are thought to cause alterations in the contractility of muscles, which leads to contractures. In vitro and in situ studies have demonstrated that in distal arthrogryposis, there are mutations in genes that encode troponin T, troponin I, and beta tropomyosin. These mutations increase ATPase and may alter calcium sensitivity, leading to increased contractility of developing fast twich muscles. The increased contractility then causes contractures.3 Alterations in the regulation of myosin heavy chains by the MYHC gene is also believed to be a cause of some forms of distal arthrogryposis.4
In central etiologies, there may be decreased corticospinal tract activation of spinal cord motor neurons or spinal cord motor neurons may be directly injured.
In congenital myopathies, there may be alterations in genes than encode mysosin light chains in skeletal muscle. Genetic alterations have also been observed in congenital myopathy and muscular dystrophy, which can affect A-type lamins and glycosylation, which can affect contractility.
In mothers with myasthenia gravis, maternal antibodies may block the acetylcholine receptors in the fetus, which can decrease fetal movement and cause contractures.5