Arthrogryposis Multiplex Congenita: Comprehensive Review from a Neuromuscular Standpoint

Arthrogryposis multiplex congenita (AMC) is a diverse group of conditions characterized by multiple joint contractures. Although individually rare, these disorders are estimated to affect 1 in 3000-5000 live births. Their common pathophysiological mechanism is fetal akinesia, a sustained reduction of fetal movement that may arise from intrinsic disturbances-such as central nervous system malformations, motor neuronopathies, neuropathies, neuromuscular junction defects, congenital myopathies, muscular dystrophies, or metabolic diseases-or from extrinsic factors including uterine constraint, maternal illness, infections, or toxic exposures. Reduced fetal motion leads to relatively uniform clinical manifestations, known as the fetal akinesia deformation sequence (FADS), which is characterized by craniofacial anomalies, pulmonary hypoplasia, growth restriction, and contractures. Currently, AMC is classified by clinical features, such as distal arthrogryposis or lethal congenital contracture syndromes. However, advances in molecular genetics have shown wide variability among conditions classified into the same category. Prognosis is widely variable, ranging from lethal perinatal forms to non-progressive mild conditions. This review discusses AMC etiologies from a topographic standpoint, considering the different levels of the motor system involved, by combining current clinical, genetic, and pathophysiological information.