Teratogen update: Maternal myasthenia gravis as a cause of congenital arthrogryposis

Background: Arthrogryposis multiplex congenita (AMC) is defined as nonprogr essive congenital contractures that generally result from lack of fetal mov ement in utero. AMC is a feature of many congenital disorders caused by gen etic, environmental, or other factors. One rare cause of AMC is maternal my asthenia gravis (MG). This is an autoimmune disorder, caused by antibodies to the nicotinic acetylcholine receptor (AChR), and resulting in weakness o f voluntary muscles. In 10-15% of babies born to MG mothers, transient sign s of MG are noted after placental transfer of anti-AChR antibodies. In a fe w cases, AMC predominates. Methods: We review the role of antibodies to AChR in MG and in AMC associat ed with maternal antibodies to AChR. Results: In anti-AChR antibody-associated AMC, fetal or neonatal death is c ommon; other deformities or CNS abnormalities are common as well. The condi tion usually recurs in each pregnancy unless the mother is treated for MG, but some mothers are asymptomatic. The maternal antibodies cross the placen ta and block the function of the fetal isoform of the AChR leading to fetal paralysis. Injection of maternal plasma into pregnant mice results in AMC in mouse fetuses. Some women with recurrent AMC in their babies have no det ectable anti-AChR suggesting the presence of antibodies to other fetal musc le or neuronal proteins. Conclusions: Although rare, anti-AChR-associated AMC is potentially treatab le and can be diagnosed by a routine antibody test. The mouse model can be used to investigate the role of these and other maternal antibodies in caus ing congenital conditions. (C) 2000 Wiley-Liss, Inc.