The etiology of arthrogryposis (multiple congenital contracture)

In laboratory animals, prenatal contractures have been induced by viruses, neuromuscular blocking agents, toxins, insecticides, hyperthermia, and limb immobilization. In agricultural animals, prenatal contractures are related to pregnant animals foraging on plants containing toxic alkaloids. Epizootics of prenatal contractures in cattle have been related to Akabane viral infections, which can now be prevented by vaccination. Human arthrogryposis (multiple congenital contracture) may occur in any synovial joint in a large variety of combinations. Several lethal syndromes commonly associated with prenatal contractures (Pena Shokeir 1 and 11, Potter's) provide supportive evidence for the following concept of prenatal contracture etiology. Evidence is provided that indicates that the following multiple etiologic factors are related to production of human arthrogryposis: mutagenic agents, mitotic abnormalities, toxic chemicals or drugs, hyperthermia, neuromuscular blocking agents, and mechanical immobilization. These multiple factors mediate their effect via the central nervous system (craniospinal motor neuraxis), motor end-plates, or by primary degeneration of muscle. The resultant effect is loss of muscle mass with imbalance of muscle power at the joints, which provokes a collagenic response (Law of the Connective Tissue). The collagenic response consists of partial replacement of muscle volume and collagenous thickening of the joint capsules. The latter process leads to joint fixation.