title: Neuropathic pain in two-generation twins carrying the sodium channel Nav1.7 functional variant R1150W.
abstract: We present clinical, neuropathological, and molecular genetic findings of a family with a new pain phenotype of the sodium channel gene SCN9A polymorphism R1150W. A 46-year-old woman presented with a 5-year history of episodic temperature- and exercise-dependent burning pain of the feet and lower legs associated with numbness of the distal upper and lower limbs. Her monozygotic twin sister and their mother and her twin presented similar symptoms. Clinical evaluation was normal except for a mild distal sensory deficit in fingers and feet. Electrophysiological testing was unremarkable, as were serum and cerebrospinal fluid laboratory findings. Skin biopsies of the distal lower limbs revealed an epidermal nerve fiber density at the lower limit of normal. Myelinated dermal nerve fibers showed elongated nodes of Ranvier, but normal distribution of nodal and paranodal proteins. Genetic testing for ion channel-associated pain disorders revealed an amino acid R1150W substitution of the Nav1.7 sodium channel. The combination of a Nav1.7 polymorphism with dysmyelinating features in small-caliber peripheral nerves has not been described before and may suggest an explanation for the clinical syndrome in our patients. Treatment with the sodium channel blocker lamotrigine provided some relief, consistent with a role of sodium channel dysfunction in the pain syndrome of this family.
authors.affiliation: Department of Neurology, Caritas Medical Center, Saarbrücken, Germany; Department of Neurology, RWTH Aachen University Hospital, Aachen, Germany.
authors.forename: Judith U
authors.initials: JU
authors.lastname: Harrer
authors.affiliation: Department of Neurology, University of Würzburg, Würzburg, Germany.
authors.forename: Nurcan
authors.initials: N
authors.lastname: Uçeyler
authors.affiliation: Department of Neurology, University of Würzburg, Würzburg, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Doppler
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA; Center for Neuroscience and Regeneration Research, Veterans Affairs Medical Center, West Haven, CT 06516, USA.
authors.forename: Tanya Z
authors.initials: TZ
authors.lastname: Fischer
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA; Center for Neuroscience and Regeneration Research, Veterans Affairs Medical Center, West Haven, CT 06516, USA.
authors.forename: Sulayman D
authors.initials: SD
authors.lastname: Dib-Hajj
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA; Center for Neuroscience and Regeneration Research, Veterans Affairs Medical Center, West Haven, CT 06516, USA.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Waxman
authors.affiliation: Department of Neurology, University of Würzburg, Würzburg, Germany. Electronic address: sommer@uni-wuerzburg.de.
authors.forename: Claudia
authors.initials: C
authors.lastname: Sommer
mesh_terms: D005260:Female; D006801:Humans; D008875:Middle Aged; D062556:NAV1.7 Voltage-Gated Sodium Channel / Q000235:genetics*; D009437:Neuralgia / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
chemical_list: D062556:NAV1.7 Voltage-Gated Sodium Channel; C486866:SCN9A protein, human
keywords: Polymorphism; R1150W; SCN9A; Sodium channel; Twin