title: Severe familial paroxysmal exercise-induced dyskinesia.
abstract: Familial paroxysmal exercise-induced dyskinesia (PED) is a rare movement disorder that is mostly caused by mutations in the solute carrier family 2, member 1 (SLC2A1) gene and inherited in an autosomal dominant manner. Clinical, laboratory, and genetic studies were performed in three family members. The proband's symptoms were recorded in a private video. He was placed on clonazepam. The 42-year-old proband presented with a 34-year-history of "dancing fits" suggesting a psychogenic aetiology. They occurred spontaneously or were triggered by physical exercise with a frequency up to six episodes per month, duration up to 30 min and no impairment of consciousness. Cerebrospinal fluid-(CSF)-to-blood glucose ratio was slightly reduced (0.59) and electroencephalograms were unremarkable. His 63-year-old father had less severe symptoms with spontaneous recovery before age of 45. The proband and his 38-year-old only brother also reported daily absence episodes early in the morning with an onset at age three and spontaneous recovery before age 15. Genetic testing revealed a novel c.972G>A, p.S324S heterozygous variant in the SLC2A1 gene in three patients. No splicing defects at the RNA level could be demonstrated. Five milligrams per day of clonazepam allowed for excellent control of PED. PED may produce a broad range of bizarre movements mimicking psychogenic movement disorders. A positive family history suggests an organic aetiology. PED can effectively be treated with clonazepam. Clinical manifestations, autosomal dominant inheritance and CSF findings suggest a causative role of the SLC2A1 gene, although no splicing defect at the RNA level could be demonstrated for the novel variant. Additional studies such as exome sequencing are indicated.
authors.affiliation: Movement Disorders Section, Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany, Tacik.Pawel@mh-hannover.de.
authors.forename: Pawel
authors.initials: P
authors.lastname: Tacik
authors.forename: Sebastian
authors.initials: S
authors.lastname: Loens
authors.forename: Christoph
authors.initials: C
authors.lastname: Schrader
authors.forename: Sabine
authors.initials: S
authors.lastname: Gayde-Stephan
authors.forename: Saskia
authors.initials: S
authors.lastname: Biskup
authors.forename: Dirk
authors.initials: D
authors.lastname: Dressler
mesh_terms: D000328:Adult; D002819:Chorea / Q000209:etiology* / Q000235:genetics; D004252:DNA Mutational Analysis; D004569:Electroencephalography; D015444:Exercise; D005192:Family Health; D051272:Glucose Transporter Type 1 / Q000235:genetics*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics
chemical_list: D051272:Glucose Transporter Type 1; C495677:SLC2A1 protein, human
references.citation: Ann Neurol. 2005 Jan;57(1):111-8
references.pmid: 15622525
references.citation: Ann Neurol. 1999 Mar;45(3):344-52
references.pmid: 10072049
references.citation: Mov Disord. 1997 Nov;12(6):1007-12
references.pmid: 9399228
references.citation: J Clin Invest. 2008 Jun;118(6):2157-68
references.pmid: 18451999
references.citation: Ann Neurol. 1995 Oct;38(4):571-9
references.pmid: 7574453
references.citation: J Neurol. 2011 Feb;258(2):316-7
references.pmid: 20830593
references.citation: Mov Disord. 2009 Aug 15;24(11):1684-8
references.pmid: 19630075
references.citation: Mov Disord. 2010 Feb 15;25(3):275-81
references.pmid: 20063428
references.citation: J Neurol. 2014 Mar;261(3):589-99
references.pmid: 24413642
references.citation: Ann Neurol. 2011 Dec;70(6):996-1005
references.pmid: 22190371
references.citation: Epilepsia. 2012 Dec;53(12):e204-7
references.pmid: 23106342
references.citation: J Neurol. 2014 Mar;261(3):615-6
references.pmid: 24487825
references.citation: Epilepsia. 2012 Sep;53(9):1503-10
references.pmid: 22812641
references.citation: Parkinsonism Relat Disord. 2011 Jul;17(6):479-81
references.pmid: 21530357
references.citation: Brain. 2010 Mar;133(Pt 3):655-70
references.pmid: 20129935
references.citation: Brain Dev. 2009 Aug;31(7):545-52
references.pmid: 19304421
references.citation: Neurology. 2010 Aug 3;75(5):432-40
references.pmid: 20574033
references.citation: Brain. 2008 Jul;131(Pt 7):1831-44
references.pmid: 18577546
references.citation: Dev Med Child Neurol. 2010 Jun;52(6):583-6
references.pmid: 20187889
references.citation: Epilepsia. 2010 Dec;51(12):2466-9
references.pmid: 21204808
references.citation: Seizure. 2013 Dec;22(10):803-11
references.pmid: 23890838
references.citation: J Neurol. 2013 Jan;260(1):93-9
references.pmid: 22752065