Association of arthrogryposis multiplex congenita with maternal antibodies inhibiting fetal acetylcholine receptor function.

Arthrogryposis multiplex congenita (AMC), characterized by multiple joint contractures developing in utero, results from lack of fetal movement. Some cases are genetically de- termined, but AMC occasionally complicates pregnancy in patients with myasthenia gravis (MG) suggesting involve- ment of circulating maternal antibodies. We previously demonstrated antibodies that inhibited the function of fetal acetylcholine receptor (AChR) in one healthy woman with an obstetric history of recurrent AMC. Here we study sera from this woman, from one other with a similar history, and from three (one asymptomatic) whose babies had neonatal MG and AMC. All five maternal sera had high titers of anti- bodies that inhibited a -Bungarotoxin ( a -BuTx) binding to fetal AChR, and their sera markedly inhibited fetal AChR function with little effect on adult AChR function. More- over, in a further survey, 3 of 20 sera from anti-AChR nega- tive AMC mothers inhibited fetal AChR function signifi- cantly at 1:100 dilution. These results demonstrate the role of antibodies to fetal AChR and perhaps other muscle anti- gens in some cases of AMC. More generally, they suggest that placental transfer of antibodies directed at fetal anti- gens should be considered as a cause of other recurrent fetal or perinatal disorders. ( J. Clin. Invest. 1996. 98:2358-2363.)