title: Paroxysmal itch caused by gain-of-function Nav1.7 mutation.
abstract: Itch is a common experience. It can occur in the course of systemic diseases and can be a manifestation of allergies or a consequence of diseases affecting the somatosensory pathway. We describe a kindred characterized by paroxysmal itch caused by a variant in SCN9A gene encoding for the Nav1.7 sodium channel. Patients underwent clinical and somatosensory profile assessment by quantitative sensory testing, nerve conduction study, autonomic cardiovascular reflex, and sympathetic skin response examination, skin biopsy with quantification of intraepidermal nerve fiber density, and SCN9A mutational analysis. The index patient, her mother, and a sister presented with a stereotypical clinical picture characterized by paroxysmal itch attacks involving the shoulders, upper back, and upper limbs, followed by transient burning pain, and triggered by environmental warmth, hot drinks, and spicy food. Somatosensory profile assessment demonstrated a remarkably identical pattern of increased cold and pain thresholds and paradoxical heat sensation. Autonomic tests were negative, whereas skin biopsy revealed decreased intraepidermal nerve fiber density in 2 of the 3 patients. All affected members harbored the 2215A>G I739V substitution in exon 13 of SCN9A gene. Pregabalin treatment reduced itch intensity and attack frequency in all patients. The co-segregation of the I739V variant in the affected members of the family provides evidence, for the first time, that paroxysmal itch can be related to a mutation in sodium channel gene.
authors.affiliation: Neurological Unit, University-Hospital "S. Maria della Misericordia", Udine, Italy Neuroalgology and Headache Unit, IRCCS Foundation "Carlo Besta" Neurological Institute, Milan, Italy Department of Neurology, Maastricht University Medical Center, Maastricht, The Netherlands Department of Neurology, Spaarne Hospital, Hoofddorp, The Netherlands Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, and Center for Neuroscience and Regeneration Research, Veterans Affairs Medical Center, West Haven, CT, USA.
authors.forename: Grazia
authors.initials: G
authors.lastname: Devigili
authors.forename: Roberto
authors.initials: R
authors.lastname: Eleopra
authors.forename: Tiziana
authors.initials: T
authors.lastname: Pierro
authors.forename: Raffaella
authors.initials: R
authors.lastname: Lombardi
authors.forename: Sara
authors.initials: S
authors.lastname: Rinaldo
authors.forename: Christian
authors.initials: C
authors.lastname: Lettieri
authors.forename: Catharina G
authors.initials: CG
authors.lastname: Faber
authors.forename: Ingemar S J
authors.initials: ISJ
authors.lastname: Merkies
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Waxman
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lauria
mesh_terms: D000328:Adult; D000982:Antipruritics / Q000627:therapeutic use; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D062556:NAV1.7 Voltage-Gated Sodium Channel / Q000235:genetics*; D010146:Pain / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D017288:Pain Threshold / Q000502:physiology; D010812:Physical Stimulation; D000069583:Pregabalin; D011537:Pruritus / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D000982:Antipruritics; D062556:NAV1.7 Voltage-Gated Sodium Channel; C486866:SCN9A protein, human; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid
keywords: Burning pain; Itch; Neuropathic pain; Paroxysmal; SCN9A; Small nerve fiber; Sodium channels