title: Muscle channelopathies: recent advances in genetics, pathophysiology and therapy.
abstract: OBJECTIVE
  This article reviews recent advances in clinical, genetic, diagnostic and pathophysiological aspects of the skeletal muscle channelopathies.
  
  
  RESULTS
  Genetic advances include the use of the minigene assay to confirm pathogenicity of splice site mutations of CLC-1 chloride channels and a new gene association for Andersen-Tawil syndrome. Mutations causing a gating pore current have been established as a pathomechanism for hypokalaemic periodic paralysis. Mutations in nonchannel genes, including the mitochondrial mATP6/8 genes, have been linked to channelopathy-like episodic weakness. Advances in diagnostic tools include the use of MRI and muscle velocity recovery cycles to evaluate myotonia congenita patients. Specific neonatal presentations of sodium channel myotonia are now well documented. An international multicentre placebo-controlled randomized clinical trial established that mexiletine is an effective therapy in the nondystrophic myotonias. This is the first evidence-based treatment for a skeletal muscle channelopathy. Recent evidence in mouse models indicated that bumetanide can prevent attacks of hypokalaemic periodic paralysis, but this has not yet been tested in patient trials.
  
  
  CONCLUSIONS
  Advances in genetic, clinical, diagnostic and pathomechanistic understanding of skeletal muscle channelopathies are being translated into improved therapies. Mexiletine is the first evidence-based treatment for nondystrophic myotonias. Bumetanide is effective in preventing attacks in mouse models of hypokalaemic periodic paralysis and now needs to be tested in patients.
authors.affiliation: aDepartment of Molecular Neuroscience, MRC Centre for Neuromuscular Diseases, Institute of Neurology, University College London bNational Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: Suetterlin
authors.forename: Roope
authors.initials: R
authors.lastname: Männikkö
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hanna
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics; D053447:Channelopathies / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D004195:Disease Models, Animal; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics; D009135:Muscular Diseases / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D009154:Mutation
chemical_list: D000951:Antigens, Neoplasm; D026901:Membrane Transport Proteins; C510061:SLC45A2 protein, human