P.379Fetal Acetylcholine Receptor Inactivation Syndrome (FARIS): A Potentially Treatable Autoimmune Disorder Mimicking a Wide Range of Genetic Neuromuscular Conditions

Fetal acetylcholine receptor inactivation syndrome (FARIS) is due to in utero exposure to maternal antibodies targeting the fetal acetylcholine receptor (AChR) α subunit, and characterized by myopathic features persisting beyond 3 months of age. Here we report 18 new FARIS cases from 14 families. In 10/18 pregnancies there was no preceding maternal MG diagnosis. Resuscitation at birth was required in 13/18 cases. Two infants with arthrogryposis multiplex congenita (AMC) died in infancy. Surviving cases showed marked hypotonia (n=16), facial weakness (n=16), contractures (n=11), respiratory and bulbar impairment requiring at least intermittent ventilation, and nasogastric tube/PEG-feeding (n=16). Most patients improved over time, acquiring ambulation and speech, however, facial and bulbar symptoms, velopharyngeal incompetence and motor delay were common residual features. Novel associations included intellectual impairment, diaphragmatic paresis (n=6), hearing impairment (n=3) pyloric stenosis (n=2), and cryptorchidism (in 4/10 males). Oral Salbutamol proved an effective therapy (n=6 cases) whilst other MG treatments had little or no effect. This is the largest series of FARIS reported to date, expanding the phenotypic spectrum of this probably under-recognized condition. The diagnosis requires a high degree of suspicion, particularly in the offspring of still asymptomatic mothers, where other neuromuscular disorders may initially be suspected. Apart from the most severe cases, the majority improve over time, with a typical combination of residual symptoms. Novel associations implicate antibody-mediated mechanisms in features such as sensorineural deafness where those have not been previously suspected. Severity correlates to timing and intensity of maternal treatment during pregnancy, emphasizing the importance of correct diagnosis with a view to reducing maternal antibody load and improving outcome in subsequent pregnancies. Salbutamol therapy should be considered.