title: Painful small fiber neuropathy with gastroparesis: A new phenotype with a novel mutation in the SCN10A gene.
abstract: Gain-of-function mutations in the SCN10A gene (encoding the Nav1.8 voltage gated sodium channel) have been reported in a small number of patients. All presented with predominantly painful sensory neuropathy, congruent with the expression of Nav1.8 in nociceptive sensory neurons of the dorsal root ganglion. Only a few had mild autonomic symptoms, including dry eyes and mouth, orthostatic dizziness, palpitations, diarrhea and constipation. The underlying mechanism of the autonomic symptoms in these patients is unclear. We describe a 37-year-old woman with severe progressive gastroparesis and diffuse painful small fiber sensory neuropathy that started at age 32. Due to the severe dysphagia she could not ingest solid food, and lost eight kilograms. The gastroparesis was documented by esophageal manometry and gastric scintigraphy. The neuropathic pain started distally and then intensified and spread to most body areas. The patient harbored a novel heterozygous mutation: c.G4915A:p.D1639N in the SCN10A gene. To the best of our knowledge, this is the first description of such a phenotype due to a Nav1.8 mutation. Thus, our study expands the clinical spectrum of Nav1.8 associated disorders, and suggests that mutations in this sodium channel should be considered in patients with gastrointestinal motility dysfunction and painful neuropathy.
authors.affiliation: Department of Neurology, Wolfson Medical Center, Ha-Lokhamim St 62, Holon 58100, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: ronda@post.tau.ac.il.
authors.forename: Ron
authors.initials: R
authors.lastname: Dabby
authors.affiliation: Department of Neurology, Wolfson Medical Center, Ha-Lokhamim St 62, Holon 58100, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Menachem
authors.initials: M
authors.lastname: Sadeh
authors.affiliation: Division of Gastroenterology, Rabin Medical Center, Beilinson Hospital, Petach Tikva, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Yelena
authors.initials: Y
authors.lastname: Broitman
authors.affiliation: Molecular Genetics Laboratory, Wolfson Medical Center, Holon, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Keren
authors.initials: K
authors.lastname: Yosovich
authors.affiliation: Division of Gastroenterology, Rabin Medical Center, Beilinson Hospital, Petach Tikva, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ram
authors.initials: R
authors.lastname: Dickman
authors.affiliation: Molecular Genetics Laboratory, Wolfson Medical Center, Holon, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Esther
authors.initials: E
authors.lastname: Leshinsky-Silver
mesh_terms: D000328:Adult; D004916:Erythromelalgia / Q000150:complications / Q000235:genetics*; D005260:Female; D005727:Ganglia, Spinal; D018589:Gastroparesis / Q000150:complications / Q000235:genetics*; D006801:Humans; D009154:Mutation; D062559:NAV1.8 Voltage-Gated Sodium Channel / Q000235:genetics*; D009619:Nociceptors; D010146:Pain / Q000150:complications / Q000235:genetics*; D010523:Peripheral Nervous System Diseases / Q000150:complications / Q000235:genetics*; D010641:Phenotype
chemical_list: D062559:NAV1.8 Voltage-Gated Sodium Channel
keywords: Autonomic neuropathy; Gastroparesis; Na(v)1.8 sodium channel; Neuropathic pain; SCN10A; Small fiber neuropathy