Objective-To improve the accuracy of genotype prediction and guide genetic testing in patients with muscle channelopathies we applied and refined specialised electrophysiological exercise test parameters.Methods-We studied 56 genetically confirmed patients and 65 controls using needle electromyography, the long exercise test, and short exercise tests at room temperature, after cooling, and rewarming.Results-Concordant amplitude-and-area decrements were more reliable than amplitude-only measurements when interpreting patterns of change during the short exercise tests. Concordant amplitude-and-area pattern I and pattern II decrements of >20% were 100% specific for PMC and MC respectively. When decrements at room temperature and after cooling were <20%, a repeat short exercise test after rewarming was useful in patients with myotonia congenita. Area measurements and rewarming distinguished true temperature sensitivity from amplitude reduction due to cold-induced slowing of muscle fibre conduction. In patients with negative short exercise tests, symptomatic eye closure myotonia predicted sodium channel myotonia over myotonia congenita. Distinctive 'tornado-shaped' neuromyotonia-like discharges may be seen in patients with paramyotonia congenita. In the long exercise test, area decrements from pre-exercise baseline were more sensitive than amplitude decrements-from-maximum-CMAP in patients with Andersen-Tawil syndrome. Possible ethnic differences in the normative data of the long exercise test argue for the use of appropriate ethnically-matched controls.Interpretation-Concordant CMAP amplitude-and-area decrements of >20% allow more reliable interpretation of the short exercise tests and aid accurate DNA-based diagnosis. In patients

Objectives: To obtain minimum point prevalence rates for the skeletal muscle channelopathies and to evaluate the frequency distribution of mutations associated with these disorders.Methods: Analysis of demographic, clinical, electrophysiologic, and genetic data of all patients assessed at our national specialist channelopathy service. Only patients living in the United Kingdom with a genetically defined diagnosis of nondystrophic myotonia or periodic paralysis were eligible for the study. Prevalence rates were estimated for England, December 2011.Results: A total of 665 patients fulfilled the inclusion criteria, of which 593 were living in England, giving a minimum point prevalence of 1.12/100,000 (95% confidence interval [CI] 1.03-1.21). Disease-specific prevalence figures were as follows: myotonia congenita 0.52/100,000 (95% CI 0.46-0.59), paramyotonia congenita 0.17/100,000 (95% CI 0.13-0.20), sodium channel myotonias 0.06/100,000 (95% CI 0.04-0.08), hyperkalemic periodic paralysis 0.17/100,000 (95% CI 0.13-0.20), hypokalemic periodic paralysis 0.13/100,000 (95% CI 0.10-0.17), and Andersen-Tawil syndrome (ATS) 0.08/100,000 (95% CI 0.05-0.10). In the whole sample (665 patients), 15 out of 104 different CLCN1 mutations accounted for 60% of all patients with myotonia congenita, 11 out of 22 SCN4A mutations for 86% of paramyotonia congenita/sodium channel myotonia pedigrees, and 3 out of 17 KCNJ2 mutations for 42% of ATS pedigrees. Conclusion:We describe for the first time the overall prevalence of genetically defined skeletal muscle channelopathies in England. Despite the large variety of mutations observed in patients with nondystrophic myotonia and ATS, a limited number accounted for a large proportion of cases. Neurology â 2013;80:1472-1475 GLOSSARY ATS 5 Andersen-Tawil syndrome; CACNA1S 5 calcium channel, voltage-dependent, L type, a 1S subunit gene; CI 5 confidence interval; CLCN1 5 chloride channel, voltage-sensitive 1 gene; HyperPP 5 hyperkalemic periodic paralysis; HypoPP 5 hypokalemic periodic paralysis; KCNJ2 5 potassium inwardly rectifying channel, subfamily J, member 2 gene; MC 5 myotonia congenita; NDM 5 nondystrophic myotonias; PMC 5 paramyotonia congenita; PP 5 periodic paralyses; SCM 5 sodium channel myotonias; SCN4A 5 sodium channel, voltage-gated, type 4, a subunit gene.Nondystrophic myotonias (NDM) and periodic paralyses (PP) comprise a heterogeneous group of skeletal muscle disorders caused by mutations in genes encoding ion channels.e1 NDM include myotonia congenita (MC), paramyotonia congenita (PMC), and the sodium channel myotonias (SCM). PP encompass hypokalemic periodic paralysis (HypoPP), hyperkalemic periodic paralysis (HyperPP), and Andersen-Tawil syndrome (ATS). These are autosomal dominant disorders except for MC, which is inherited in either a dominant or recessive manner. e1 Although significant progress in the clinical, electrophysiologic, and genetic characterization of the skeletal muscle channelopathies has taken place in the past 2 decades, their actual prevalence rem...