ASSOCIATION OF ARTHROGRYPOSIS MULTIPLEX CONGENITA WITH MATERNAL ANTIBODIES INHIBITING FETAL ACETYLCHOLINE-RECEPTOR FUNCTION

Arthrogryposis multiplex congenita (AMC), characterized by multiple jo int contractures developing in utero, results from lack of fetal movem ent, Some cases are genetically determined, but AMC occasionally compl icates pregnancy in patients with myasthenia gravis (MG) suggesting in volvement of circulating maternal antibodies, We previously demonstrat ed antibodies that inhibited the function of fetal acetylcholine recep tor (AChR) in one healthy woman with an obstetric history of recurrent AMC, Here we study sera from this woman, from one other with a simila r history, and from three (one asymptomatic) whose babies had neonatal MG and AMC, All five maternal sera had high titers of antibodies that inhibited alpha-Bungarotoxin (alpha-BuTx) binding to fetal AChR, and their sera markedly inhibited fetal AChR function with little effect o n adult AChR function. Moreover, in a further survey, 3 of 20 sera fro m anti-AChR negative AMC mothers inhibited fetal AChR function signifi cantly at 1:100 dilution, These results demonstrate the role of antibo dies to fetal AChR and perhaps other muscle antigens in some cases of AMC, More generally, they suggest that placental transfer of antibodie s directed at fetal antigens should be considered as a cause of other recurrent fetal or perinatal disorders.