The Emerging Spectrum of Fetal Acetylcholine Receptor Antibody-Related Disorders (farad)

Introduction: In utero exposure to maternal fetal acetylcholine receptor (fAChR) antibodies may lead to Arthrogryposis Multiplex Congenita (AMC) and, apparently rarer, milder myopathic presentations. We report the full fAChR-associated spectrum and analyze the relationship between maternal treatments and offspring outcome. Methods: Retrospective case note review; immunological analysis (RIA, CBA) of AChR antibody profiles; literature review. Results: We identified 46 cases with exposure to maternal fAChR antibodies, without previous diagnosis of maternal MG in more than half. Offspring death occurred in 11/46 (23.9%). Weakness, contractures, bulbar and respiratory involvement were prominent at presentation. Facial weakness (25/34; 73.5%), variable peripheral weakness (14/32; 43.8%), velopharyngeal insufficiency (VPI) (18/24; 75%) and feeding difficulties (16/36; 44.4%) were common sequelae. Other features included hearing loss (12/32; 37.5%), diaphragmatic paresis (5/35; 14.3%), CNS involvement (7/40; 17.5%) and pyloric stenosis (3/37; 8.1%). Oral salbutamol used empirically in 16/35 (47.5%) offspring resulted in improvement in 13/16 (81.3%). Combining our series with all previously published literature, we found that compared to untreated mothers (64/85), maternal treatment (21/85), in particular IVIG/PLEX administered early in pregnancy, resulted in a significant reduction in offspring deaths (P<0.05) and other complications. Conclusion: Presentations due to in utero exposure to maternal fAChR antibodies are probably more common than currently recognized. Particularly where mothers are asymptomatic, these potentially preventable presentations may lead to the erroneous suspicion of a genetic (neuromuscular) disorder but are vitally important to diagnose correctly to improve outcomes in future pregnancies. Oral salbutamol is a potentially effective treatment option in affected offspring.