Clinical manifestations, electrophysiology, pathology and gene diagnosis in a Chinese family of endplate acetylcholinesterase deficient congenital myasthenic syndrome

Abstract

Objective To report the clinical presentations, lab tests, electrophysiological studies, muscle biopsy and the genetic investigation of the endplate acetylcholinesterase deficient congenital myasthenic syndrome (CMS). Methods The proband, a 15 years old girl, presented ptosis, exercise-intolerant and delayed motor developmental milestones from birth. The disease progressed slowly. After 12 years old, the girl showed limited eye movements, decreased ventilation and scoliosis. Her elder sister had the same symptoms and died of severe respiratory infection when she was one year old. Profound blood tests, electrophysiological studies, muscle biopsy, next generation sequencing and pedigree validation were performed on the proband. Results The electrophysiological studies showed repeated compound muscle action potential in response to single nerve stimulus, decremental response following 3-5 Hz repetitive nerve stimulation and rapid decrement-slight increment-decrement-stable response course following 10-50 Hz repetitive nerve stimulation. Electromyography (EMG) showed slight myogenic changes. Single fiber-EMG disclosed increased jitter. The muscle biopsy indicated unspecific myopathic changes. DNA analysis revealed a compound heterozygous mutations, c. 1082delC and c. 1190G>A, in COLQ gene. The pedigree tests validated the mutations were inherited from father and mother separately. Conclusions The COLQ-mutant endplate acetylcholinesterase deficient CMS has distinctive electrophysiological features, which is the hint for diagnosis. Treatment with ephedrine is recommended to this type of CMS. Key words: Congenital myasthenic syndrome; Endplate acetylcholinesterase deficiency; Collagen Q; Compound muscle action potential; Next-generation sequencing; Ephedrine