A clinical geneticist believes that a rare variant in the SCN9A gene could be responsible for at least a part of my symptoms. The variant is extremely rare (1 in 1.4 million alleles) and not found in healthy people. The gene is associated with small fibre neuropathy which would fit, but there is also an apparently hereditory orthostatic intolerance which is giving me some doubts because SCN9A is usually mentioned in the context of pain rather than orthostatic intolerance. Can we construct a credible narrative where a SCN9A variant is mostly causing orthostatic intolerance and some dysautonomia?
Curious to know if you get anywhere with this, especially as from memory we have an awful lot of symptom overlap. Have you had the genetic testing to confirm this mutation already? After diagnosing SFN my neurologist suggested sending me to a sodium channel mutation expert. In his words I was somewhat of an anomaly and unlike his hundreds of other patients with SFN/dysautonomia. I think said expert was Prof David Bennett in Oxford. Unfortunately my neurologist ended up on long-term sick and I was discharged from his clinic
Yes it has been confirmed. PS: but for now it's just a hypothesis that it has something to do with my symptoms. I'm waiting to hear from my neurologist on the next steps.
I’m awaiting my results for sodium channel mutations which has taken nearly 2 years to come back due to a paperwork mix up. I’m not sure how it would fit with dysautonomia. I share both that and severe widespread pain. Have you had any response to sodium channel blockers? I haven’t.
@Hoopoe, good question. here’s a recent paper published on autonomic dysfunction and variants. Genetic landscape of congenital insensitivity to pain and hereditary sensory and autonomic neuropathies Brain, Volume 146, Issue 12, December 2023 https://doi.org/10.1093/brain/awad328 Publications by Steven Waxman (Yale) and associates might also be worth checking out.
We have two threads on SCN9A, one from 2020 — Case report: Association of small-fiber polyneuropathy with three previously unassociated rare missense SCN9A variants (2020) and from 2023 — Integrative miRNA–mRNA profiling of human epidermis: unique signature of SCN9A painful neuropathy (2023, Brain) See also papers in thread on voltage-gated sodium channels in pain — Identification and targeting of a unique NaV1.7 domain driving chronic pain (2023, Proceedings of the National Academy of Sciences)
https://pubmed.ncbi.nlm.nih.gov/25957174/ It sounds like it might be relevant. Nav1.7 is also expressed in the hypothalamus where, among other things, it's involved in the release of vasopressin which is relevant to orthostatic intollerance.
