Muscle channelopathies: recent advances in genetics, pathophysiology and therapy

作者：Suetterlin Karen; Maennikkoe Roope; Hanna Michael G^*

来源：Current Opinion in Neurology, 2014, 27(5): 583-590.

DOI：10.1097/WCO.0000000000000127

• nondystrophic myotonia
• periodic paralysis
• skeletal muscle channelopathy

Purpose of review
This article reviews recent advances in clinical, genetic, diagnostic and pathophysiological aspects of the skeletal muscle channelopathies.
Recent findings
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.
Summary
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.

• 出版日期2014-10