Schwartz-Jampel syndrome (SJS) is a rare genetic disorder characterized by abnormalities of the skeletal muscles, including myotonic myopathy, bone dysplasia, joint contractures and/or dwarfism. Affected individuals may also have small, fixed facial features and various abnormalities of the eyes, some of which may cause impaired vision. The range and severity of symptoms may vary from case to case. SJS results from hypomorphic mutations in the HSPG2 gene, which encodes perlecan, a large heparan sulfate proteoglycan (HSPG) that is present in all basement membranes. It is involved in cell adhesion, growth factor signaling, and maintenance of the basement membrane. SJS has been described as an inherited disorder associated with peripheral nerve hyperexcitability. However, whether the spontaneous activity resulting from perlecan deficiency originates in the central nervous system, peripheral nerve, or skeletal muscle remains to be clearly established. This study provides a detailed electrophysiological characterization of the SJS mutant mouse and locates the origin of the abnormal muscle activity in SJS. The homozygous mutant mice develop at the adult stage an abnormal phenotype mimicking SJS. On electromyography (EMG) perlecan deficiency results in neuromyotonic discharges that were observed in all muscles except the diaphragm. Furthermore, these discharges were not influenced by general anesthesia and disappeared with curare. They persisted after complete motor nerve section and terminated only with Wallerian degeneration, as signaled by the onset of fibrillation potentials. These results suggest a distal axonal localization of the generator of neuromyotonia in SJS.

This work was funded by the AFM.

Références : Muscle Nerve. 2009 Apr 14. [Epub ahead of print]