Peripheral nerve hyperexcitability with preterminal nerve and neuromuscular junction remodeling is a hallmark of Schwartz-Jampel syndrome.

Abstract

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.

• Authors: Stéphanie Bauché, Delphine Boerio, Claire-Sophie Davoine, Véronique Bernard, Morgane Stum, Cécile Bureau, Michel Fardeau, Norma Beatriz Romero, Bertrand Fontaine, Jeanine Koenig, Daniel Hantaï, Antoine Gueguen, Emmanuel Fournier, Bruno Eymard, Sophie Nicole
• Journal: Neuromuscular disorders : NMD (Neuromuscul Disord) Vol. 23 Issue 12 Pg. 998-1009 (Dec 2013) ISSN: 1873-2364 [Electronic] England
• PMID: 24011702 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Calcium-Binding Proteins
• Myelin Basic Protein
• Neurofilament Proteins
• Receptors, Cholinergic
• S100 Proteins
• phospholamban
• neurofilament protein H
• ERBB3 protein, human
• MUSK protein, human
• Receptor Protein-Tyrosine Kinases
• Receptor, ErbB-3

Topics

• Adult
• Calcium-Binding Proteins (metabolism)
• Electromyography
• Humans
• Male
• Myelin Basic Protein (metabolism)
• Neural Conduction (physiology)
• Neurofilament Proteins (metabolism)
• Neuromuscular Junction (metabolism, pathology, physiopathology, ultrastructure)
• Osteochondrodysplasias (pathology)
• Peripheral Nerves (metabolism, pathology, physiopathology, ultrastructure)
• Receptor Protein-Tyrosine Kinases (metabolism)
• Receptor, ErbB-3 (metabolism)
• Receptors, Cholinergic (metabolism)
• S100 Proteins (metabolism)