What causes paramyotonia in the United Kingdom? Common and new SCN4A mutations revealed

Neurology. 2008 Jan 1;70(1):50-3. doi: 10.1212/01.wnl.0000287069.21162.94.


Objective: To study the clinical and genetic features in a large cohort of UK patients with sodium channel paramyotonia congenita.

Methods: We conducted a UK-wide clinical and molecular genetic study of patients presenting with a phenotype suggestive of paramyotonia congenita.

Results: We identified 42 affected individuals (28 kindreds). All cases met our core criteria for a clinical diagnosis of paramyotonia congenita. Seventy-five percent of patients (32 patients/20 kindreds) had SCN4A mutations. Twenty-nine subjects from 18 kindreds had exon 22 and 24 mutations, confirming these exons to be hot spots. Unexpectedly, 3 of these subjects harbored mutations previously described with potassium-aggravated myotonia (G1306A, G1306E). We identified two new mutations (R1448L and L1436P). Ten cases (8 kindreds) without mutations exhibited paramyotonia congenita with prominent pain and weakness.

Conclusions: This study identifies two new mutations, confirms SCN4A as a common cause of paramyotonia congenita in the UK, and suggests further allelic and possibly genetic heterogeneity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Arginine / genetics
  • Cohort Studies
  • Exons / genetics
  • Female
  • Humans
  • Leucine / genetics
  • Male
  • Mutation*
  • Myotonic Disorders / epidemiology*
  • Myotonic Disorders / genetics*
  • Myotonic Disorders / physiopathology
  • NAV1.4 Voltage-Gated Sodium Channel
  • Neural Conduction / physiology
  • Proline / genetics
  • Sodium Channels / genetics*
  • United Kingdom / epidemiology
  • United Kingdom / ethnology


  • NAV1.4 Voltage-Gated Sodium Channel
  • SCN4A protein, human
  • Sodium Channels
  • Arginine
  • Proline
  • Leucine