Résumé :
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Congenital myopathies are clinico-pathological entities essentially defined by characteristic histopathological and ultrastructural findings in the muscle biopsy in patients with early-onset weakness. The three "classic" groups are represented by the nemaline myopathies, the core myopathies and the centro-nuclear myopathies, each of which now shows an increasing degree of genetic and clinical heterogeneity, with increasing associated clinical spectra. On the histopathological level there are overlapping histological and clinical features that may combine typical features of more then one classical entity (such in rod-core disease). Clearly, mutations in the same gene may underly more then one clinico-pathological entity and more then one clinical entity. This blurring of traditional boundaries does suggest that there may be pathomechanisms that are spanning across various congenital myopathies. Work in biopsy material and in animal models, especially in mouse and zebrafish have helped define such pathophysiologic concepts that reach across the boundaries of previously defined entities. The shared pathophysiological concept with currently the most support from clinical and animal work concerns the regulation of excitation contraction coupling via the functional unit at the triad, increased oxidative stress, abnormal autophagy regulation, and abnormalities of regulation and function of the contractile (myofibrillar) apparatus. I will attempt to relay these findings back to the clinic and highlight potential implications for the development of therapeutic approaches to the congenital myopathies.
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