MYASTHENIA GRAVIS: P.374Surrogacy prevents recurrence of fetal acetylcholine receptor inactivation syndrome

Abstract

Fetal acetylcholine receptor inactivation syndrome (FARIS) is a recently recognized congenital myopathy due to in utero exposure to maternal acetylcholine receptor (AChR) antibodies directed against the fetal AChR. Unlike transient neonatal myasthenia gravis, FARIS extends well beyond the neonatal period. We review the literature, report the second case of FARIS born to an asymptomatic mother, and describe how surrogacy successfully prevented the development of FARIS. We describe a non-consanguineous couple whose first 3 pregnancies were complicated by FARIS. All 3 fetuses had polyhydramnios and arthrogryposis. Only one child survived the neonatal period, a term female born with weakness, respiratory and bulbar insufficiency. She improved markedly during childhood, but still has significant facial weakness. Extensive investigations in the siblings, including whole exome sequencing, were negative. The mother, who is completely asymptomatic for myasthenia gravis (MG), was then found to have elevated AChR antibodies, clinching the diagnosis of FARIS. This couple then had recourse to a surrogate, using their own ovum and sperm. Ultrasounds were normal. A female child was born at term, without any feature of FARIS. At 3 months, she is healthy and developing normally. We found 12 other FARIS cases from 6 different families. Only one other mother was asymptomatic for MG. Children who survive the neonatal period typically improve, but have persistent myopathic facies. The recurrence risk is extremely high. More aggressive MG treatment during pregnancy appears to lessen the severity, but does not prevent the development of FARIS. FARIS is a myopathy caused by in utero exposure to maternal AChR antibodies directed against the fetal AChR. Diagnosing FARIS is particularly challenging when the mother is not known for MG, but has important clinical implications for future pregnancies. Therefore, FARIS should be included in the differential diagnosis of congenital myopathies.