Abstract |
Many clinical features of autosomal centronuclear myopathies (CNM) and X-linked myotubular myopathy ( XLMTM) are common to congenital myasthenic syndromes (CMS). We describe three children whose clinical and electrophysiological findings originally suggested CMS, in whom CNM was diagnosed pathologically, though not yet genetically characterised. A fourth case, with XLMTM, also showed electrophysiological features of a neuromuscular transmission defect. Three (including the XLMTM case) showed improved strength with acetylcholinesterase inhibitor treatment. We also studied neuromuscular junction structure and function in the MTM1 knockdown zebrafish model of XLMTM, demonstrating abnormal neuromuscular junction organization; anticholinesterase therapy resulted in marked clinical response. These observations suggest that a neuromuscular transmission defect may accompany CNM and contribute to muscle weakness. Muscle biopsy should be considered in infants suspected to have CMS, especially if treatment response is incomplete, or no CMS gene mutation is identified. Treatment with acetylcholinesterase inhibitors may benefit some CNM patients. This warrants further confirmation.
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Authors | Stephanie A Robb, Caroline A Sewry, James J Dowling, Lucy Feng, Tom Cullup, Sue Lillis, Stephen Abbs, Melissa M Lees, Jocelyn Laporte, Adnan Y Manzur, Ravi K Knight, Kerry R Mills, Michael G Pike, Wolfram Kress, David Beeson, Heinz Jungbluth, Matthew C Pitt, Francesco Muntoni |
Journal | Neuromuscular disorders : NMD
(Neuromuscul Disord)
Vol. 21
Issue 6
Pg. 379-86
(Jun 2011)
ISSN: 1873-2364 [Electronic] England |
PMID | 21440438
(Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2011 Elsevier B.V. All rights reserved. |
Chemical References |
- Cholinesterase Inhibitors
- Zebrafish Proteins
- MTM1 protein, zebrafish
- Protein Tyrosine Phosphatases, Non-Receptor
- Pyridostigmine Bromide
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Topics |
- Adolescent
- Animals
- Biopsy
- Child
- Cholinesterase Inhibitors
(pharmacology, therapeutic use)
- Disease Models, Animal
- Electromyography
- Female
- Gene Knockout Techniques
- Humans
- Infant
- Male
- Muscle, Skeletal
(pathology)
- Myopathies, Structural, Congenital
(drug therapy, genetics, physiopathology)
- Neuromuscular Junction
(drug effects, physiopathology)
- Protein Tyrosine Phosphatases, Non-Receptor
(genetics)
- Pyridostigmine Bromide
(pharmacology, therapeutic use)
- Synaptic Transmission
(drug effects, physiology)
- Treatment Outcome
- Zebrafish
- Zebrafish Proteins
(genetics)
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