Résumé :
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Schwartz-Jampel syndrome (SJS) is a recessive disorder characterized by muscle stiffness with spontaneous activity at the rest EMG. SJS is due to mutations of perlecan, a proteoglycan of basement membranes. The characteristics of spontaneous activity in SJS remain unclear since previous reports were divergent. Whether the divergence is due to heterogeneity of the sample studied, is specific to the disease or depends on the investigator is unknown. Here, we investigated two adult patients (one male and one female) with a mild form of SJS to help clarifying this issue.Perlecan deficiency due to loss-of-function mutations was observed in the two patients, thereby confirming the diagnosis of SJS. Standardized EMG protocols showed normal nerve conduction, normal neuromuscular transmission and normal compound muscle action potentials for the two cases. Conventional needle-EMG detected minor myopathic changes of the motor unit potentials in the male patient and spontaneous activities in all muscles tested of the two cases. The spontaneous activities showed constant amplitude and frequency with low firing rates, uniform shape, and abrupt stop, and fulfilled the AAEM definition of complex repetitive discharges. They were triggered by a brief muscle contraction or were spontaneous and displayed a reproductive pattern. Muscle biopsies done at the age of 3.7 (biceps) and 35 years (deltoid) were analyzed for the male patient. Signs of muscle dystrophy with variability of fiber size, fibers with centralized nuclei and vacuoles were present only in the biopsy done at the younger age. Predominance of type I fibers with grouping of type II fibers was observed at both ages. The histological survey of neuromuscular junctions (deltoid muscle) done at the age of 35 years showed partial denervation, reinnervation by terminal sprouting and reduced amount of acetylcholinesterase according to the known role of perlecan in the anchorage of this enzyme to the synaptic basement membrane. Our results suggest that complex repetitive discharges at the rest EMG, mild muscle dystrophy that does not progress with age and neuromuscular junction remodeling on the muscle biopsy are predominant neuromuscular changes in SJS. Together with the recent investigation done on a SJS mouse model, our results favor the hypothesis of a presynaptic origin for the spontaneous activity responsible for the muscle stiffness in SJS. Supported by AFM, INSERM, CNRS, UPMC, MESR.
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