title: 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.affiliation: Inserm, U975, Centre de recherche de l'Institut du Cerveau et de la Moelle Épinière (CRICM), Groupe hospitalier Pitié-Salpêtrière, Paris, France; Université Pierre et Marie Curie Paris 6, UMRS975, Paris, France; CNRS, UMR7225, Paris, France; Ecole Pratique des Hautes Etudes, Paris, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Bauché
authors.forename: Delphine
authors.initials: D
authors.lastname: Boerio
authors.forename: Claire-Sophie
authors.initials: CS
authors.lastname: Davoine
authors.forename: Véronique
authors.initials: V
authors.lastname: Bernard
authors.forename: Morgane
authors.initials: M
authors.lastname: Stum
authors.forename: Cécile
authors.initials: C
authors.lastname: Bureau
authors.forename: Michel
authors.initials: M
authors.lastname: Fardeau
authors.forename: Norma Beatriz
authors.initials: NB
authors.lastname: Romero
authors.forename: Bertrand
authors.initials: B
authors.lastname: Fontaine
authors.forename: Jeanine
authors.initials: J
authors.lastname: Koenig
authors.forename: Daniel
authors.initials: D
authors.lastname: Hantaï
authors.forename: Antoine
authors.initials: A
authors.lastname: Gueguen
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Fournier
authors.forename: Bruno
authors.initials: B
authors.lastname: Eymard
authors.forename: Sophie
authors.initials: S
authors.lastname: Nicole
mesh_terms: D000328:Adult; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004576:Electromyography; D006801:Humans; D008297:Male; D004676:Myelin Basic Protein / Q000378:metabolism; D009431:Neural Conduction / Q000502:physiology; D016900:Neurofilament Proteins / Q000378:metabolism; D009469:Neuromuscular Junction / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D010009:Osteochondrodysplasias / Q000473:pathology*; D010525:Peripheral Nerves / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology* / Q000648:ultrastructure; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D020893:Receptor, ErbB-3 / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000378:metabolism; D009418:S100 Proteins / Q000378:metabolism; D000099211:Phospholamban
chemical_list: D002135:Calcium-Binding Proteins; D004676:Myelin Basic Protein; D016900:Neurofilament Proteins; D020794:Receptor Protein-Tyrosine Kinases; D020893:Receptor, ErbB-3; D011950:Receptors, Cholinergic; D009418:S100 Proteins; D000099211:Phospholamban; C051774:neurofilament protein H; C581292:ERBB3 protein, human; C095714:MUSK protein, human
keywords: Basement membrane; Muscle stiffness; Neuromuscular junction; Peripheral nerve hyperexcitability; Perlecan; Schwartz-Jampel syndrome