title: Prevalence study of genetically defined skeletal muscle channelopathies in England.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Medical Research Council Centre for Neuromuscular Diseases, National Hospital for Neurology and Neurosurgery and University College London Institute of Neurology, Queen Square, London, UK.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Horga
authors.forename: Dipa L
authors.initials: DL
authors.lastname: Raja Rayan
authors.forename: Emma
authors.initials: E
authors.lastname: Matthews
authors.forename: Richa
authors.initials: R
authors.lastname: Sud
authors.forename: Doreen
authors.initials: D
authors.lastname: Fialho
authors.forename: Siobhan C M
authors.initials: SC
authors.lastname: Durran
authors.forename: James A
authors.initials: JA
authors.lastname: Burge
authors.forename: Simona
authors.initials: S
authors.lastname: Portaro
authors.forename: Mary B
authors.initials: MB
authors.lastname: Davis
authors.forename: Andrea
authors.initials: A
authors.lastname: Haworth
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hanna
mesh_terms: D000328:Adult; D053447:Channelopathies / Q000453:epidemiology* / Q000235:genetics*; D018118:Chloride Channels / Q000235:genetics; D003627:Data Interpretation, Statistical; D030541:Databases, Genetic; D004739:England / Q000453:epidemiology; D005260:Female; D006801:Humans; D020514:Hypokalemic Periodic Paralysis / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000502:physiology*; D009135:Muscular Diseases / Q000453:epidemiology* / Q000235:genetics*; D009154:Mutation / Q000235:genetics / Q000502:physiology; D009222:Myotonia / Q000453:epidemiology / Q000235:genetics; D020967:Myotonic Disorders / Q000453:epidemiology / Q000235:genetics; D062553:NAV1.4 Voltage-Gated Sodium Channel / Q000235:genetics; D010245:Paralyses, Familial Periodic / Q000453:epidemiology / Q000235:genetics; D020513:Paralysis, Hyperkalemic Periodic / Q000453:epidemiology / Q000235:genetics; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D015995:Prevalence; D015222:Sodium Channels / Q000235:genetics / Q000502:physiology; D006113:United Kingdom / Q000453:epidemiology
chemical_list: C086321:CLC-1 channel; D018118:Chloride Channels; C489457:KCNJ2 protein, human; D062553:NAV1.4 Voltage-Gated Sodium Channel; D024661:Potassium Channels, Inwardly Rectifying; C106251:SCN4A protein, human; D015222:Sodium Channels