Abstract
Skeletal muscle ion channelopathies (SMICs) are a large heterogeneous group of rare genetic disorders caused by mutations in genes encoding ion channel subunits in the skeletal muscle mainly characterized by myotonia or periodic paralysis, potentially resulting in long-term disabilities. However, with the development of new molecular technologies, new genes and new phenotypes, including progressive myopathies, have been recently discovered, markedly increasing the complexity in the field. In this regard, new advances in SMICs show a less conventional role of ion channels in muscle cell division, proliferation, differentiation, and survival. Hence, SMICs represent an expanding and exciting field. Here, we review current knowledge of SMICs, with a description of their clinical phenotypes, cellular and molecular pathomechanisms, and available treatments.
Highlights
Introduction for TherapyCells 2021, 10, 1521.Primary ion channelopathies are rare diseases caused by mutations in genes encoding ion channel subunits
The first ion channelopathy was identified in hyperkalemic periodic paralysis, a genetic disease affecting exclusively skeletal muscles and caused by mutations in the SCN4A gene encoding the alpha subunit of voltage-gated sodium channel Nav1.4, which expression is limited to the skeletal muscle fiberfibers [1]
Other SCN4A mutations are responsible for Sodium channel myotonia (SCM), which can be distinguished from Paramyotonia congenita (PMC) by the lack of both paradoxical myotonia and episodes of flaccid paralysis [10]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Hypotonia, delayed motor milestones, facial involvement (ophthalmoplegia), progressive muscle weakness (mainly axial). Floppy infant; non-progressive/slowly progressive myopathy; joint contractures n.a. Hypotonia, delayed motor milestones, dysmorphic facial features and facial weakness, and progressive muscle weakness n.a. Perinuclear and subsarcolemmal nemaline bodies, wide variation in fiber size with type 1 fiber predominance and atrophy, increased internal nuclei. From arthrogryposis multiplex congenital and fetal akinesia, ocular, bulbar and respiratory symptoms, delayed motor milestones, to mild adult muscle weakness. Neonatal hypotonia; ocular, bulbar, respiratory muscle involvement, with predominant weakness of cervical, wrist, finger, and finger extensor muscles. Non-specific bulbar (dysarthria), neck, recurrent respiratory crises, and limb progressive muscle weakness and fatigability. Double CMAP on single nerve stimuli ENG episodic respiratory insufficiency, bulbar (swallowing), and proximal limb muscle weakness.
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