title: Fetal acetylcholine receptor inactivation syndrome: A myopathy due to maternal antibodies.
abstract: BACKGROUND
  Transient neonatal myasthenia gravis (TNMG) affects a proportion of infants born to mothers with myasthenia gravis (MG). Symptoms usually resolve completely within the first few months of life, but persistent myopathic features have been reported in a few isolated cases.
  
  
  METHODS
  Here we report 8 patients from 4 families born to mothers with clinically manifest MG or mothers who were asymptomatic but had elevated acetylcholine receptor (AChR) antibody levels.
  
  
  RESULTS
  Clinical features in affected infants ranged from a mild predominantly facial and bulbar myopathy to arthrogryposis multiplex congenita. Additional clinical findings included hearing impairment, pyloric stenosis, and mild CNS involvement. In all cases, antibodies against the AChR were markedly elevated, although not always specific for the fetal AChR γ subunit. There was a correlation between maternal symptoms; the timing, intensity, and frequency of maternal treatment; and neonatal outcome.
  
  
  CONCLUSIONS
  These findings suggest that persistent myopathic features following TNMG may be more common than currently recognized. Fetal AChR inactivation syndrome should be considered in the differential diagnosis of infants presenting with unexplained myopathic features, in particular marked dysarthria and velopharyngeal incompetence. Correct diagnosis requires a high degree of suspicion if the mother is asymptomatic but is crucial considering the high recurrence risk for future pregnancies and the potentially treatable nature of this condition. Infants with a history of TNMG should be followed up for subtle myopathic signs and associated complications.
authors.affiliation: Department of Pediatric Neurology (Y.H., S.B., D.C., M.L., H.J.), Evelina's Children Hospital, Guy's & St. Thomas' Hospital NHS Foundation Trust, London, United Kingdom; Department of Clinical Neurology (Y.H., L.W.J., A.V.), Oxford University, Oxford; Department of Neurology (F.N.), Department of Neonatology (A.L.), Randall Division for Cell and Molecular Biophysics (H.J.), Muscle Signaling Section, and Department of Basic and Clinical Neuroscience Division (H.J.), IoP, King's College, London, United Kingdom; Dubowitz Neuromuscular Centre (S.R.), Great Ormond Street Hospital for Children, London, United Kingdom; Unit of Clinical Neurophysiology (R.D.), Department of Neuroscience and Mental Health and Neonatal Intensive Care Unit (M.F.), IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy; and Department of Pediatrics (A.P.B.), Rigshospitalet, Copenhagen University Hospital, Denmark.
authors.forename: Yael
authors.initials: Y
authors.lastname: Hacohen
authors.affiliation: Department of Pediatric Neurology (Y.H., S.B., D.C., M.L., H.J.), Evelina's Children Hospital, Guy's & St. Thomas' Hospital NHS Foundation Trust, London, United Kingdom; Department of Clinical Neurology (Y.H., L.W.J., A.V.), Oxford University, Oxford; Department of Neurology (F.N.), Department of Neonatology (A.L.), Randall Division for Cell and Molecular Biophysics (H.J.), Muscle Signaling Section, and Department of Basic and Clinical Neuroscience Division (H.J.), IoP, King's College, London, United Kingdom; Dubowitz Neuromuscular Centre (S.R.), Great Ormond Street Hospital for Children, London, United Kingdom; Unit of Clinical Neurophysiology (R.D.), Department of Neuroscience and Mental Health and Neonatal Intensive Care Unit (M.F.), IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy; and Department of Pediatrics (A.P.B.), Rigshospitalet, Copenhagen University Hospital, Denmark.
authors.forename: Leslie W
authors.initials: LW
authors.lastname: Jacobson
authors.affiliation: Department of Pediatric Neurology (Y.H., S.B., D.C., M.L., H.J.), Evelina's Children Hospital, Guy's & St. Thomas' Hospital NHS Foundation Trust, London, United Kingdom; Department of Clinical Neurology (Y.H., L.W.J., A.V.), Oxford University, Oxford; Department of Neurology (F.N.), Department of Neonatology (A.L.), Randall Division for Cell and Molecular Biophysics (H.J.), Muscle Signaling Section, and Department of Basic and Clinical Neuroscience Division (H.J.), IoP, King's College, London, United Kingdom; Dubowitz Neuromuscular Centre (S.R.), Great Ormond Street Hospital for Children, London, United Kingdom; Unit of Clinical Neurophysiology (R.D.), Department of Neuroscience and Mental Health and Neonatal Intensive Care Unit (M.F.), IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy; and Department of Pediatrics (A.P.B.), Rigshospitalet, Copenhagen University Hospital, Denmark.
authors.forename: Susan
authors.initials: S
authors.lastname: Byrne
authors.affiliation: Department of Pediatric Neurology (Y.H., S.B., D.C., M.L., H.J.), Evelina's Children Hospital, Guy's & St. Thomas' Hospital NHS Foundation Trust, London, United Kingdom; Department of Clinical Neurology (Y.H., L.W.J., A.V.), Oxford University, Oxford; Department of Neurology (F.N.), Department of Neonatology (A.L.), Randall Division for Cell and Molecular Biophysics (H.J.), Muscle Signaling Section, and Department of Basic and Clinical Neuroscience Division (H.J.), IoP, King's College, London, United Kingdom; Dubowitz Neuromuscular Centre (S.R.), Great Ormond Street Hospital for Children, London, United Kingdom; Unit of Clinical Neurophysiology (R.D.), Department of Neuroscience and Mental Health and Neonatal Intensive Care Unit (M.F.), IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy; and Department of Pediatrics (A.P.B.), Rigshospitalet, Copenhagen University Hospital, Denmark.
authors.forename: Fiona
authors.initials: F
authors.lastname: Norwood
authors.affiliation: Department of Pediatric Neurology (Y.H., S.B., D.C., M.L., H.J.), Evelina's Children Hospital, Guy's & St. Thomas' Hospital NHS Foundation Trust, London, United Kingdom; Department of Clinical Neurology (Y.H., L.W.J., A.V.), Oxford University, Oxford; Department of Neurology (F.N.), Department of Neonatology (A.L.), Randall Division for Cell and Molecular Biophysics (H.J.), Muscle Signaling Section, and Department of Basic and Clinical Neuroscience Division (H.J.), IoP, King's College, London, United Kingdom; Dubowitz Neuromuscular Centre (S.R.), Great Ormond Street Hospital for Children, London, United Kingdom; Unit of Clinical Neurophysiology (R.D.), Department of Neuroscience and Mental Health and Neonatal Intensive Care Unit (M.F.), IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy; and Department of Pediatrics (A.P.B.), Rigshospitalet, Copenhagen University Hospital, Denmark.
authors.forename: Abhimanu
authors.initials: A
authors.lastname: Lall
authors.affiliation: Department of Pediatric Neurology (Y.H., S.B., D.C., M.L., H.J.), Evelina's Children Hospital, Guy's & St. Thomas' Hospital NHS Foundation Trust, London, United Kingdom; Department of Clinical Neurology (Y.H., L.W.J., A.V.), Oxford University, Oxford; Department of Neurology (F.N.), Department of Neonatology (A.L.), Randall Division for Cell and Molecular Biophysics (H.J.), Muscle Signaling Section, and Department of Basic and Clinical Neuroscience Division (H.J.), IoP, King's College, London, United Kingdom; Dubowitz Neuromuscular Centre (S.R.), Great Ormond Street Hospital for Children, London, United Kingdom; Unit of Clinical Neurophysiology (R.D.), Department of Neuroscience and Mental Health and Neonatal Intensive Care Unit (M.F.), IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy; and Department of Pediatrics (A.P.B.), Rigshospitalet, Copenhagen University Hospital, Denmark.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Robb
authors.affiliation: Department of Pediatric Neurology (Y.H., S.B., D.C., M.L., H.J.), Evelina's Children Hospital, Guy's & St. Thomas' Hospital NHS Foundation Trust, London, United Kingdom; Department of Clinical Neurology (Y.H., L.W.J., A.V.), Oxford University, Oxford; Department of Neurology (F.N.), Department of Neonatology (A.L.), Randall Division for Cell and Molecular Biophysics (H.J.), Muscle Signaling Section, and Department of Basic and Clinical Neuroscience Division (H.J.), IoP, King's College, London, United Kingdom; Dubowitz Neuromuscular Centre (S.R.), Great Ormond Street Hospital for Children, London, United Kingdom; Unit of Clinical Neurophysiology (R.D.), Department of Neuroscience and Mental Health and Neonatal Intensive Care Unit (M.F.), IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy; and Department of Pediatrics (A.P.B.), Rigshospitalet, Copenhagen University Hospital, Denmark.
authors.forename: Robertino
authors.initials: R
authors.lastname: Dilena
authors.affiliation: Department of Pediatric Neurology (Y.H., S.B., D.C., M.L., H.J.), Evelina's Children Hospital, Guy's & St. Thomas' Hospital NHS Foundation Trust, London, United Kingdom; Department of Clinical Neurology (Y.H., L.W.J., A.V.), Oxford University, Oxford; Department of Neurology (F.N.), Department of Neonatology (A.L.), Randall Division for Cell and Molecular Biophysics (H.J.), Muscle Signaling Section, and Department of Basic and Clinical Neuroscience Division (H.J.), IoP, King's College, London, United Kingdom; Dubowitz Neuromuscular Centre (S.R.), Great Ormond Street Hospital for Children, London, United Kingdom; Unit of Clinical Neurophysiology (R.D.), Department of Neuroscience and Mental Health and Neonatal Intensive Care Unit (M.F.), IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy; and Department of Pediatrics (A.P.B.), Rigshospitalet, Copenhagen University Hospital, Denmark.
authors.forename: Monica
authors.initials: M
authors.lastname: Fumagalli
authors.affiliation: Department of Pediatric Neurology (Y.H., S.B., D.C., M.L., H.J.), Evelina's Children Hospital, Guy's & St. Thomas' Hospital NHS Foundation Trust, London, United Kingdom; Department of Clinical Neurology (Y.H., L.W.J., A.V.), Oxford University, Oxford; Department of Neurology (F.N.), Department of Neonatology (A.L.), Randall Division for Cell and Molecular Biophysics (H.J.), Muscle Signaling Section, and Department of Basic and Clinical Neuroscience Division (H.J.), IoP, King's College, London, United Kingdom; Dubowitz Neuromuscular Centre (S.R.), Great Ormond Street Hospital for Children, London, United Kingdom; Unit of Clinical Neurophysiology (R.D.), Department of Neuroscience and Mental Health and Neonatal Intensive Care Unit (M.F.), IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy; and Department of Pediatrics (A.P.B.), Rigshospitalet, Copenhagen University Hospital, Denmark.
authors.forename: Alfred Peter
authors.initials: AP
authors.lastname: Born
authors.affiliation: Department of Pediatric Neurology (Y.H., S.B., D.C., M.L., H.J.), Evelina's Children Hospital, Guy's & St. Thomas' Hospital NHS Foundation Trust, London, United Kingdom; Department of Clinical Neurology (Y.H., L.W.J., A.V.), Oxford University, Oxford; Department of Neurology (F.N.), Department of Neonatology (A.L.), Randall Division for Cell and Molecular Biophysics (H.J.), Muscle Signaling Section, and Department of Basic and Clinical Neuroscience Division (H.J.), IoP, King's College, London, United Kingdom; Dubowitz Neuromuscular Centre (S.R.), Great Ormond Street Hospital for Children, London, United Kingdom; Unit of Clinical Neurophysiology (R.D.), Department of Neuroscience and Mental Health and Neonatal Intensive Care Unit (M.F.), IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy; and Department of Pediatrics (A.P.B.), Rigshospitalet, Copenhagen University Hospital, Denmark.
authors.forename: Debbie
authors.initials: D
authors.lastname: Clarke
authors.affiliation: Department of Pediatric Neurology (Y.H., S.B., D.C., M.L., H.J.), Evelina's Children Hospital, Guy's & St. Thomas' Hospital NHS Foundation Trust, London, United Kingdom; Department of Clinical Neurology (Y.H., L.W.J., A.V.), Oxford University, Oxford; Department of Neurology (F.N.), Department of Neonatology (A.L.), Randall Division for Cell and Molecular Biophysics (H.J.), Muscle Signaling Section, and Department of Basic and Clinical Neuroscience Division (H.J.), IoP, King's College, London, United Kingdom; Dubowitz Neuromuscular Centre (S.R.), Great Ormond Street Hospital for Children, London, United Kingdom; Unit of Clinical Neurophysiology (R.D.), Department of Neuroscience and Mental Health and Neonatal Intensive Care Unit (M.F.), IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy; and Department of Pediatrics (A.P.B.), Rigshospitalet, Copenhagen University Hospital, Denmark.
authors.forename: Ming
authors.initials: M
authors.lastname: Lim
authors.affiliation: Department of Pediatric Neurology (Y.H., S.B., D.C., M.L., H.J.), Evelina's Children Hospital, Guy's & St. Thomas' Hospital NHS Foundation Trust, London, United Kingdom; Department of Clinical Neurology (Y.H., L.W.J., A.V.), Oxford University, Oxford; Department of Neurology (F.N.), Department of Neonatology (A.L.), Randall Division for Cell and Molecular Biophysics (H.J.), Muscle Signaling Section, and Department of Basic and Clinical Neuroscience Division (H.J.), IoP, King's College, London, United Kingdom; Dubowitz Neuromuscular Centre (S.R.), Great Ormond Street Hospital for Children, London, United Kingdom; Unit of Clinical Neurophysiology (R.D.), Department of Neuroscience and Mental Health and Neonatal Intensive Care Unit (M.F.), IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy; and Department of Pediatrics (A.P.B.), Rigshospitalet, Copenhagen University Hospital, Denmark.
authors.forename: Angela
authors.initials: A
authors.lastname: Vincent
authors.affiliation: Department of Pediatric Neurology (Y.H., S.B., D.C., M.L., H.J.), Evelina's Children Hospital, Guy's & St. Thomas' Hospital NHS Foundation Trust, London, United Kingdom; Department of Clinical Neurology (Y.H., L.W.J., A.V.), Oxford University, Oxford; Department of Neurology (F.N.), Department of Neonatology (A.L.), Randall Division for Cell and Molecular Biophysics (H.J.), Muscle Signaling Section, and Department of Basic and Clinical Neuroscience Division (H.J.), IoP, King's College, London, United Kingdom; Dubowitz Neuromuscular Centre (S.R.), Great Ormond Street Hospital for Children, London, United Kingdom; Unit of Clinical Neurophysiology (R.D.), Department of Neuroscience and Mental Health and Neonatal Intensive Care Unit (M.F.), IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy; and Department of Pediatrics (A.P.B.), Rigshospitalet, Copenhagen University Hospital, Denmark.
authors.forename: Heinz
authors.initials: H
authors.lastname: Jungbluth