IllnessSmall-fiber neuropathy, SFN; differential diagnosis

SP9988_DH

Small fiber neuropathy is characterized by severe pain attacks, typically beginning in the feet or hands. With advancing age, the pain attacks may affect other regions. Some patients experience generalized whole-body pain. The symptoms usually begin in adolescence to middle adulthood. People with small-fiber neuropathy may not experience pain that is concentrated in a very small area, such as pinpricks. Nevertheless, they suffer from hyperalgesia and allodynia. Affected individuals can also sometimes barely distinguish between hot and cold, but in some individuals the pain attacks are triggered by cold or heat. Some patients have urinary or bowel problems, episodes of palpitations, dry eyes or mouth, profuse sweating or orthostatic hypotension. Mutations in the SCN9A, SCN10A, or SCN11A genes can cause small fiber neuropathy. SCN9A gene mutations are found in ~30% of cases, SCN10A gene mutations are responsible for ~5%, pathogenic SCN11A variants are less common. In some cases, diabetes mellitus, impaired glucose tolerance, Fabry disease or celiac disease and Sjogren's syndrome cause the disorder, possibly also sarcoidosis or HIV infection. Small fiber neuropathy is inherited in an autosomal dominant manner. The diagnostic yield by molecular genetics barely exceeds 35% of patients. When the genetic cause of small fiber neuropathy is unknown or when the disease is due to another disorder, the mode of inheritance remains unclear. Therefore, the clinical diagnosis is not refuted when DNA testing yields negative results.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1163/

• Alias: Natrium-Ionenkanalkrankheit-assoziierte Small-Fiber-Neuropathie, SFN
• Alias: Ulcero-mutilating neuropathy (RAB7A)
• Allelic: Carpal tunnel syndrome, familial (TTR)
• Allelic: Cerebellar ataxia, deafness + narcolepsy, AD (DNMT1)
• Allelic: Dystransthyretinemic hyperthyroxinemia (TTR)
• Allelic: Episodic pain syndrome, familial, 3 (SCN11A)
• Allelic: Fabry disease, cardiac variant (GLA)
• Allelic: Spastic paraplegia 3A, AD (ATL1)
• Amyloidosis, hereditary, transthyretin-related (TTR)
• Charcot-Marie-Tooth disease, type 2B (RAB7A)
• Episodic pain syndrome, familial, 1 (TRPA1)
• Episodic pain syndrome, familial, 2 (SCN10A)
• Erythermalgia, primary (SCN9A)
• Fabry disease (GLA)
• Neuropathy, hereditary sensory + autonomic, type IA (SPTLC1)
• Neuropathy, hereditary sensory + autonomic, type IC (SPTLC2)
• Neuropathy, hereditary sensory + autonomic, type VII (SCN11A)
• Neuropathy, hereditary sensory, type ID (ATL1)
• Neuropathy, hereditary sensory, type IE (DNMT1)
• Neuropathy, hereditary sensory, type IF (ATL3)
• Small fiber neuropathy (SCN9A)