Genetic aspects of sodium channelopathy in small fiber neuropathy

J. G. J. Hoeijmakers, Ingemar S. J. Merkies, M. M. Gerrits, Stephen G. Waxman, C. G. Faber*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Small fiber neuropathy (SFN) is a disorder typically dominated by neuropathic pain and autonomic dysfunction, in which the thinly myelinated Ad-fibers and unmyelinated C-fibers are selectively injured. The diagnosis SFN is based on a reduced intraepidermal nerve fiber density and/or abnormal thermal thresholds in quantitative sensory testing. The etiologies of SFN are diverse, although no apparent cause is frequently seen. Recently, SCN9A-gene variants (single amino acid substitutions) have been found in similar to 30% of a cohort of idiopathic SFN patients, producing gain-of-function changes in sodium channel NaV1.7, which is preferentially expressed in small diameter peripheral axons. Functional testing showed that these variants altered fast inactivation, slow inactivation or resurgent current and rendered dorsal root ganglion neurons hyperexcitable. In this review, we discuss the role of NaV1.7 in pain and highlight the molecular genetics and pathophysiology of SCN9A-gene variants in SFN. With increasing knowledge regarding the underlying pathophysiology in SFN, the development of specific treatment in these patients seems a logical target for future studies.
Original languageEnglish
Pages (from-to)351-358
JournalClinical Genetics
Issue number4
Publication statusPublished - Oct 2012


  • Nav1
  • 7
  • SCN9A
  • small fiber neuropathy
  • sodium channelopathy


Dive into the research topics of 'Genetic aspects of sodium channelopathy in small fiber neuropathy'. Together they form a unique fingerprint.

Cite this