Mutation in Na_v 1.7 causes high olfactory sensitivity.

Area of Science:

• Neuroscience
• Genetics
• Clinical Medicine

Background:

• Mutations in the SCN9A gene, encoding Nav1.7 sodium channels, are linked to pain disorders.
• Gain-of-function missense mutations in Nav1.7 are causal in primary erythromelalgia.

Observation:

• A 50-year-old woman presented with a decade of burning foot pain, abdominal pain attacks, and heightened smell sensitivity (hyperosmia).
• Clinical, laboratory, and electrophysiological tests were normal, but olfactory testing revealed high acuity.
• Quantitative sensory testing showed low trigeminal detection thresholds, lower limb hyperalgesia, and eventual thermal sensory loss, alongside reduced epidermal nerve fiber density.

Findings:

• Genetic analysis identified a heterozygous mutation in SCN9A Exon 20 (c.3734A>G, p.N1245S).
• Standard sodium channel inhibitors were ineffective for pain relief.
• Topical ambroxol provided pain reduction, and continuous odor exposure offered mood stabilization and short-term pain relief.

Implications:

• This case report details middle-age onset erythromelalgia associated with a likely pathogenic Nav1.7 mutation.
• The findings suggest a presumed gain-of-function in olfactory and pain sensation pathways.
• This case expands understanding of SCN9A-related channelopathies and potential therapeutic avenues.