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SGCE and myoclonus dystonia: motor characteristics, diagnostic criteria and clinical predictors of genotype

Lookup NU author(s): Professor Patrick Chinnery

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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 a parts per thousand currency sign10 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.

Publication metadata

Author(s): Peall KJ, Kurian MA, Wardle M, Waite AJ, Hedderly T, Lin JP, Smith M, Whone A, Pall H, White C, Lux A, Jardine PE, Lynch B, Kirov G, O'Riordan S, Samuel M, Lynch T, King MD, Chinnery PF, Warner TT, Blake DJ, Owen MJ, Morris HR

Publication type: Article

Publication status: Published

Journal: Journal of Neurology

Year: 2014

Volume: 261

Issue: 12

Pages: 2296-2304

Print publication date: 01/12/2014

Online publication date: 11/09/2014

Acceptance date: 31/08/2014

ISSN (print): 0340-5354

ISSN (electronic): 1432-1459

Publisher: Springer

URL: http://dx.doi.org/10.1007/s00415-014-7488-3

DOI: 10.1007/s00415-014-7488-3

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