title: Clinical neuroimaging and electrophysiological assessment of three DYT6 dystonia families.
abstract: The purpose of the study was to delineate clinical and electrophysiological characteristics as well as laryngoscopical and transcranial ultrasound (TCS) findings in THAP1 mutation carriers (MutC). According to recent genetic studies, DYT6 (THAP1) gene mutations are an important cause of primary early-onset dystonia. In contrast to DYT1 mutations, THAP1 mutations are associated with primary early-onset segmental or generalised dystonia frequently involving the craniocervical region and the larynx. Blood samples from twelve individuals of three German families with DYT6 positive index cases were obtained to test for THAP1 mutations. Eight THAP1 MutC were identified. Of these, six (three symptomatic and three asymptomatic) THAP1 MutC could be clinically evaluated. Laryngoscopy was performed to evaluate laryngeal dysfunction in patients. Brainstem echogenicity was investigated in all MutC using TCS. Two of the patients had undergone bilateral pallidal DBS. In all three symptomatic MutC, early-onset laryngeal dystonia was a prominent feature. Laryngeal assessment demonstrated adductor-type dystonia in all of them. On clinical examination, the three asymptomatic MutC also showed subtle signs of focal or segmental dystonia. TCS revealed increased substantia nigra (SN) hyperechogenicity in all MutC. Intraoperative microelectrode recordings under general anesthesia in two of the patients showed no difference between THAP1 and previously operated DYT1 MutC. The presence of spasmodic dysphonia in patients with young-onset segmental or generalised dystonia is a hallmark of DYT6 dystonia. SN hyperechogenicity on TCS may represent an endophenotype in these patients. Pallidal DBS in two patients was unsatisfactory.
authors.affiliation: Department of Neurology, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Zittel
authors.forename: Christian K E
authors.initials: CK
authors.lastname: Moll
authors.forename: Norbert
authors.initials: N
authors.lastname: Brüggemann
authors.forename: Vera
authors.initials: V
authors.lastname: Tadic
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hamel
authors.forename: Meike
authors.initials: M
authors.lastname: Kasten
authors.forename: Katja
authors.initials: K
authors.lastname: Lohmann
authors.forename: Thora
authors.initials: T
authors.lastname: Lohnau
authors.forename: Susen
authors.initials: S
authors.lastname: Winkler
authors.forename: Christian
authors.initials: C
authors.lastname: Gerloff
authors.forename: Rainer
authors.initials: R
authors.lastname: Schönweiler
authors.forename: Johann
authors.initials: J
authors.lastname: Hagenah
authors.forename: Christine
authors.initials: C
authors.lastname: Klein
authors.forename: Alexander
authors.initials: A
authors.lastname: Münchau
authors.forename: Susanne A
authors.initials: SA
authors.lastname: Schneider
mesh_terms: D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D020821:Dystonic Disorders / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology*; D004569:Electroencephalography / Q000379:methods; D004594:Electrophysiology; D005260:Female; D005917:Globus Pallidus / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007818:Laryngeal Diseases / Q000175:diagnosis / Q000209:etiology; D008297:Male; D008839:Microelectrodes; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype; D017585:Ultrasonography, Doppler, Transcranial / Q000379:methods; D014832:Voice Disorders / Q000175:diagnosis / Q000209:etiology
chemical_list: D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C474080:THAP1 protein, human