title: SGCE and myoclonus dystonia: motor characteristics, diagnostic criteria and clinical predictors of genotype.
abstract: Myoclonus dystonia syndrome (MDS) is a young-onset movement disorder. A proportion of cases are due to mutations in the maternally imprinted SGCE gene. We assembled the largest cohort of MDS patients to date, and determined the frequency and type of SGCE mutations. The aim was to establish the motor phenotype in mutation carriers and utility of current diagnostic criteria. Eighty-nine probands with clinical features compatible with MDS were recruited from the UK and Ireland. Patients were phenotypically classified as "definite", "probable" or "possible" MDS according to previous guidelines. SGCE was analyzed using direct sequencing and copy number variant analysis. In those where no mutation was found, DYT1 (GAG deletion), GCH1, THAP1 and NKX2.1 genes were also sequenced. Nineteen (21.3%) probands had an SGCE mutation. Three patterns of motor symptoms emerged: (1) early childhood onset upper body myoclonus and dystonia, (2) early childhood onset lower limb dystonia, progressing later to more pronounced myoclonus and upper body involvement, and (3) later childhood onset upper body myoclonus and dystonia with evident cervical involvement. Five probands had large contiguous gene deletions ranging from 0.7 to 2.3 Mb in size with distinctive clinical features, including short stature, joint laxity and microcephaly. Our data confirms that SGCE mutations are most commonly identified in MDS patients with (1) age at onset ≤10 years and (2) predominant upper body involvement of a pure myoclonus-dystonia. Cases with whole SGCE gene deletions had additional clinical characteristics, which are not always predicted by deletion size or gene involvement.
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Hadyn Ellis Building, Maindy Road, Cardiff, CF24 4HQ, UK, PeallKJ@cardiff.ac.uk.
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Peall
authors.forename: Manju A
authors.initials: MA
authors.lastname: Kurian
authors.forename: Mark
authors.initials: M
authors.lastname: Wardle
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Waite
authors.forename: Tammy
authors.initials: T
authors.lastname: Hedderly
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Lin
authors.forename: Martin
authors.initials: M
authors.lastname: Smith
authors.forename: Alan
authors.initials: A
authors.lastname: Whone
authors.forename: Hardev
authors.initials: H
authors.lastname: Pall
authors.forename: Cathy
authors.initials: C
authors.lastname: White
authors.forename: Andrew
authors.initials: A
authors.lastname: Lux
authors.forename: Philip E
authors.initials: PE
authors.lastname: Jardine
authors.forename: Bryan
authors.initials: B
authors.lastname: Lynch
authors.forename: George
authors.initials: G
authors.lastname: Kirov
authors.forename: Sean
authors.initials: S
authors.lastname: O'Riordan
authors.forename: Michael
authors.initials: M
authors.lastname: Samuel
authors.forename: Timothy
authors.initials: T
authors.lastname: Lynch
authors.forename: Mary D
authors.initials: MD
authors.lastname: King
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Chinnery
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Warner
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Blake
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
authors.forename: Huw R
authors.initials: HR
authors.lastname: Morris
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004421:Dystonia / Q000235:genetics*; D020821:Dystonic Disorders / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D007494:Ireland / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D049031:Sarcoglycans / Q000235:genetics*; D006113:United Kingdom / Q000453:epidemiology; D055815:Young Adult
chemical_list: C526572:SGCE protein, human; D049031:Sarcoglycans