Résumé :
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In recent years the phenotypes and histological patterns associated with known structural myopathy genes has expanded (eg RYR1, TPM3, TPM2). Many of the less well defined diagnostic entities, such as cap disease and congenital fibre type disproportion appear often due to known genes. In patients with 'non-specific' histological features, identifying the genetic cause remains difficult and a re-focus on clinical features is likely to provide important diagnostic clues. A genetic diagnosis often contributes important information to guide patient management as well as genetic counselling and research. Genetic analysis remains the gold standard for confirming a clinical/histological diagnosis but accessing genetic testing is frequently difficult because genetic testing is inadequately funded in many countries. There are significant differences in pathophysiology between most structural myopathies and the muscular dystrophies, which is likely to impact on the therapies most likely to work. Significant challenges remain before gene therapy becomes routine clinical practice in muscle disease. Primary or secondary disruption to signalling pathways, ion channels and to the actin-myosin contractile unit are central to the disease process in many structural myopathies and represent targets for more conventional treatment approaches with small molecules. An intimate knowledge of the pathophysiology of each disorder will allow focused research. Surprisingly, the mechanism of weakness is still unknown for many myopathies, (eg SEPN1, MTM1, DNM2) and is often unclear for many structural genes (eg. ACTA1, TPM3, NEB). Common secondary features such as global muscle atrophy and changes to fibre size and proportion are other possible therapeutic targets, but their contribution to patient morbidity is unclear. A continued focus on 'why is the patient weak' is needed to guide therapeutic research for the structural myopathies.
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