title: Congenital myasthenic syndrome due to choline acetyltransferase mutations in infants: clinical suspicion and comprehensive electrophysiological assessment are important for early diagnosis.
abstract: Congenital myasthenic syndromes are inherited disorders caused by various defects in neuromuscular transmission. Although the typical presentation is fatigable weakness with prominent cranial involvement, neonates can lack these hallmark manifestations, and in those with choline acetyltransferase gene mutations, basal electrophysiological testing can yield negative findings. The authors report the case of a male infant presenting at birth with oculomotor and bulbofacial weakness, hypotonia, clubfoot, and severe respiratory insufficiency. Electromyography showed myogenic signs, and basal repetitive nerve stimulation yielded negative findings. Since age 6 months, the infant had progressively improved, acquiring autonomous respiration. Prolonged subtetanic repetitive nerve stimulation disclosed a marked decremental response compatible with suspected congenital myasthenic syndrome with episodic apnea. Genetic testing identified 2 novel choline acetyltransferase mutations (R470X, F580C). Keeping a high clinical suspicion of this rare condition and undertaking early comprehensive electrophysiological assessments including prolonged repetitive nerve stimulation (10 Hz for 5 minutes) can expedite the diagnosis.
authors.affiliation: 1Unit of Clinical Neurophysiology, Department of Neurological Sciences, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Robertino
authors.initials: R
authors.lastname: Dilena
authors.forename: Angela
authors.initials: A
authors.lastname: Abicht
authors.forename: Paola
authors.initials: P
authors.lastname: Sergi
authors.forename: Giacomo P
authors.initials: GP
authors.lastname: Comi
authors.forename: Alessio
authors.initials: A
authors.lastname: Di Fonzo
authors.forename: Giovanna
authors.initials: G
authors.lastname: Chidini
authors.forename: Federica
authors.initials: F
authors.lastname: Natacci
authors.forename: Sergio
authors.initials: S
authors.lastname: Barbieri
authors.forename: Hanns
authors.initials: H
authors.lastname: Lochmüller
mesh_terms: D002675:Child, Preschool; D002795:Choline O-Acetyltransferase / Q000235:genetics*; D018450:Disease Progression; D042241:Early Diagnosis; D004568:Electrodiagnosis; D004576:Electromyography; D005158:Facial Paralysis / Q000175:diagnosis / Q000209:etiology / Q000235:genetics / Q000473:pathology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D020294:Myasthenic Syndromes, Congenital / Q000150:complications / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D015835:Ocular Motility Disorders / Q000175:diagnosis / Q000209:etiology / Q000235:genetics / Q000473:pathology
chemical_list: D002795:Choline O-Acetyltransferase
keywords: choline acetyltransferase mutations; congenital myasthenic syndrome with episodic apnea; electrodiagnosis; hypotonia; neonatal respiratory paralysis; prolonged subtetanic repetitive nerve stimulation