Clinical spectrum of SCN4A-associated skeletal muscle channelopathies

Student thesis: Doctoral Thesis

Abstract

SCN4A-associated non-dystrophic myotonias are rare diseases. Only in the last few years, prospective studies evaluated the sensitivity of symptoms and signs of myotonia in large cohorts of patients, leading to the conclusion that the phenotypes are frequently much more complex than previously thought. This clinical heterogeneity can also be applied to our patient cohort. Some of the observed phenotypes and related genotypes differ from what is commonly described in literature. Our findings contribute to visualize the genotypic and phenotypic characteristics and distribution of muscular sodium channelopathies in the region of Brussels.

Further, the diagnosis of these channelopathies remains challenging. We highlighted some pitfalls in the diagnosis, based on different observations in our patient population.

Finally, we observed a previously unreported overlap between Brugada syndrome and SCN4A-associated muscular channelopathies. The possible association between these two rare diseases, is supported by several publications, demonstrating the expression of skeletal muscle voltage-gated sodium channels in the cardiac muscle. The presence of a SCN4A variant is probably not solely responsible for an arrhythmic event, but would rather act as a modifier gene in Brugada syndrome.
Date of Award18 Jun 2015
Original languageEnglish
Awarding Institution
  • Vrije Universiteit Brussel
SupervisorJacques De Keyser (Promotor), Pedro Brugada (Co-promotor), Linda De Meirleir (Jury), Sara Seneca (Jury), Jan Versijpt (Jury), Baziel van Engelen (Jury), Peter Van Den Bergh (Jury) & Jonathan Baets (Jury)

Keywords

  • SCN4A
  • non-dystrophic myotonias

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