Peripheral nerve hyperexcitability with preterminal nerve and neuromuscular junction remodeling is a hallmark of Schwartz-Jampel syndrome
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- 作者：St茅phanie Bauch茅 ; Delphine Boerio ; Claire-Sophie Davoine ; V茅ronique Bernard ; Morgane Stum ; C茅cile Bureau ; Michel Fardeau ; Norma Beatriz Romero ; Bertr ; Fontaine ; Jeanine Koenig ; Daniel Hanta茂 ; Antoine Gueguen ; Emmanuel Fournier ; Bruno Eymard ; Sophie Nicole
- 关键词：Schwartz-Jampel syndrome ; Muscle stiffness ; Peripheral nerve hyperexcitability ; Basement membrane ; Perlecan ; Neuromuscular junction
- 刊名：Neuromuscular Disorders
- 出版年：December, 2013
- 年：2013
- 卷：23
- 期：12
- 页码：998-1009
- 全文大小：2270 K
文摘
Schwartz-Jampel syndrome (SJS) is a recessive disorder with muscle hyperactivity that results from hypomorphic mutations in the perlecan gene, a basement membrane proteoglycan. Analyses done on a mouse model have suggested that SJS is a congenital form of distal peripheral nerve hyperexcitability resulting from synaptic acetylcholinesterase deficiency, nerve terminal instability with preterminal amyelination, and subtle peripheral nerve changes. We investigated one adult patient with SJS to study this statement in humans. Perlecan deficiency due to hypomorphic mutations was observed in the patient biological samples. Electroneuromyography showed normal nerve conduction, neuromuscular transmission, and compound nerve action potentials while multiple measures of peripheral nerve excitability along the nerve trunk did not detect changes. Needle electromyography detected complex repetitive discharges without any evidence for neuromuscular transmission failure. The study of muscle biopsies containing neuromuscular junctions showed well-formed post-synaptic element, synaptic acetylcholinesterase deficiency, denervation of synaptic gutters with reinnervation by terminal sprouting, and long nonmyelinated preterminal nerve segments. These data support the notion of peripheral nerve hyperexcitability in SJS, which would originate distally from synergistic actions of peripheral nerve and neuromuscular junction changes as a result of perlecan deficiency.