Résumé :
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Exercise-induced muscle stiffness occuring since childhood can be due to a genetic muscle excitability disorder. Electromyographic (EMG) examination allows to distinguish between non-dystophic myotonias (NDM, with typical myotonic bursts) and an electrically silent muscle relaxation disorder called Brody syndrome (BS; Brody, 1969). BS is related with an impairment of calcium reuptake after contraction in fast-twitch skeletal muscle fibers by sarco-endoplasmic reticulum calcium ATPase type 1 (SERCA1) encoded by ATP2A1, mutations of which are responsible for autosomal recessive BS cases (MacLennan, 1996).Our laboratory has been providing analysis of SCN4A and CLCN1 genes in NDM for several years. In some cases referred for NDM, the EMG fails to find myotonic bursts or the genetic investigation fails to find mutations in SCN4A or CLCN1. We recently set up the sequencing of ATP2A1 gene in order to diagnose BS. We identified 10 cases with ATP2A1 mutations. Four cases were previously considered as NDM, and six cases were referred explicitly as possible BS. Retrospectively, the clinical and EMG presentation of all 10 cases was evocative for the diagnosis of Brody syndrome. Main clinical elements are : (a) painless exercise-induced stiffness neither aggravated nor corrected by exercise prolongation, since childhood, with no evolution; (b) hand and eyelid action "myotonia" at clinical examination; (c) no or mild aggravation at cold; (d) absent, mild or marked harmonious hypertrophy. The main electromyographical element is an absence of electrical activity as contraction persists, with no myotonic discharges.Our ATP2A1 mutated genotypes consisted of 5 homozygous (one exon 5 deletion; four missense), 2 compound heterozygous (c.198_200del/c.2465dup, c.1742_1743del/c.2744+1 G>T) and 3 simple heterozygous (missense) genotypes. Muscle biopsy was available for 4 patients. SERCA1 immunohistochemistry was performed. SERCA1 staining was absent in type 2 fibres in 2 patients, but was present in 2 other patients. The absence or presence of SERCA1 staining correlates with the prediction of the absence or presence of protein according to mutation type.Among cases of exercise-induced stiffness, ATP2A1-related BS cases can be recognized and diagnosed at the clinical, EMG and genetic level. The SERCA1 immunostaining is not sufficient to make or exclude the diagnosis, as it may be negative or positive.
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