Image For Activity Cover
Journal Review: Expanding the genetic causes of small-fiber neuropathy: SCN genes and beyond
Journal Review: Expanding the genetic causes of small-fiber neuropathy: SCN genes and beyond

Small-fiber neuropathy (SFN) is a disorder that exclusively affects the small nerve fibers, sparing the large nerve fibers. Thinly myelinated Aδ-fibers and unmyelinated C-fibers are damaged, leading to development of neuropathic pain, thermal dysfunction, sensory symptoms, and autonomic disturbances. Although many SFNs are secondary and due to immunological causes or metabolic disturbances, the etiology is unknown in up to half of the patients. Over the years, this proportion of “idiopathic SFN” has decreased, as familial and genetic causes have been discovered, thus shifting a proportion of once “idiopathic” cases to the genetic category. After the discovery of SCN9A-gene variants in 2012, SCN10A and SCN11A variants have been found to be pathogenic in SFN. With improved accessibility of SFN diagnostic tools and genetic tests, many non-SCN variants and genetically inherited systemic diseases involving the small nerve fibers have also been described, but only scattered throughout the literature.
There are 80 SCN variants described as causing SFN, 8 genes causing hereditary sensory autonomic neuropathies (HSAN) described with pure SFN, and at least 7 genes involved in genetically inherited systemic diseases associated with SFN. This systematic review aims to consolidate and provide an updated overview on the genetic variants of SFN to date---SCN genes and beyond. Awareness of these genetic causes of SFN is imperative for providing treatment directions, prognostication, and management of expectations for patients and their health-care providers.

1)Understand and recognize the clinical features of small fiber neuropathy;
2) Develop and apply a logical approach to the diagnostic evaluation of a patient with suspected small fiber neuropathy;
3)Understand, recognize, and be able to order necessary diagnostic testing for the evaluation of genetic causes of small fiber neuropathy.  

The AANEM is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

The AANEM designates this enduring material for a maximum of 1 AMA PRA Category 1 Credits TM.  Physicians should claim only the credit commensurate with the extent of their participation in the activity. Credit expires 3/1/2026.

The authors have no conflicts of interest. 

Amanda C. Y. Chan, FRCP; Shivaram Kumar; Grace Tan, BSc (Hons); Hiu Yi Wong, MD, PhD; Jonathan J. Y. Ong, MD; Bharatendu Chandra, MD; Hua Huang, PhD; Vijay Kumar Sharma, MD; Poh San Lai, PhD.
Availability: On-Demand
Expires on Mar 01, 2026
Cost: Member: $0.00
Non-Member: $25.00
Credit Offered:
1 CME Credit
2621 Superior Drive NW Rochester, MN 55901
Phone: 507.288.0100
Fax: 507.288.1225
Powered By