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BNSU SURVEILLANCE PROJECT: MYOCLONUS DYSTONIA SYNDROME
  1. Huw Morris
  1. Cardif University

    Abstract

    Background Myoclonus Dystonia Syndrome (MDS) is a childhood onset, alcohol responsive movement disorder characterised by trunk and upper limb myoclonus and dystonia of the neck and hands. Inheritance is autosomal dominant and mutations of the maternally imprinted epsilon–sarcoglycan gene (SGCE) are identified in a proportion of cases. Single family and case series have suggested co–morbid psychiatric disorders but have not compared cases to a control group.

    Aims We aimed to establish a cohort of MDS cases to: 1) identify the rate and type of SGCE mutations, 2) systematically characterise their psychiatric and motor features.

    Methods Cases of clinically suspected Myoclonus Dystonia were recruited from adult and paediatric movement disorder clinics throughout the UK and Ireland. The project also formed one of the British Neurological Surveillance Unit (BNSU) projects allowing ABN members to electronically record cases seen during their clinical practice. Clinical information was collected by face–to–face examination or from the referring clinician. The MINI International Neuropsychiatric Interview, PHQ–9, MADRS, YBOCS and AUDIT were used to assess psychiatric disease according to DSM–IV criteria and results compared to alcohol responsive tremor control cases. DNA samples were analysed via Sanger sequencing and multiplex ligation–dependent probe amplification (MLPA).

    Results We collected 106 unrelated patients. Seventeen referrals were made via the BNSU, 12 of who responded to consent forms and questionnaires being sent from our department. Nineteen proband cases were found to have an SGCE mutation, 18% of the total cohort and near equally distributed between males and females (8M:11F). Mutations included missense (n=1), splice–site (n=3), nonsense (n=8), intra–exonic deletions (n=3) single exon deletions (n=1) and whole gene deletions (n=3), 5 of which were novel. This number increased to 27 motor affected SGCE mutation carriers when additional family members were recruited. Median age at onset of the movement disorder was 3 years. All cases had evidence of myoclonus and dystonia with the upper limbs being the most commonly affected body part. There was a higher rate of psychiatric disorders in MDS patients compared to controls (p<0.05), specifically social phobia (p<0.05) and Obsessive–Compulsive disease (OCD) (p<0.001), particularly symptoms of compulsivity (p<0.001). Additional clinical characteristics observed in those with whole gene deletions included short stature, microcephaly, joint laxity, cognitive impairment and dysarthria.

    Conclusion 19/106 samples were found to have an SGCE mutation. Mutation carriers had features consistent with the proposed diagnostic criteria, and 7 cases were identified with additional lower limb dystonia. Overall psychiatric disorders were elevated amongst the MDS cohort compared to the alcohol responsive tremor control group. OCD, in particular compulsivity, appeared to be the greatest contributor to this effect and may reflect a pleiotropic function for the SGCE gene. Genetic mutations included single exon and whole gene deletions, splice site mutations and most commonly, premature stop codon mutations. There was no clear genotype/phenotype relationship with the exception of dysmorphic features in some of the whole gene deletion cases.

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