Abstract Details

Title Tremor as a Prominent Feature in Xp22.31 Microduplication: A Novel Association

Topic Movement Disorders

Presentation(s) P05 - (-)

Poster/Presentation
Number 040

Objective

Background BACKGROUND: There are a number of well-known X-linked genetic syndromes with tremor as a distinctive feature, including FXTAS, CMTX1, Dystonia-Parkinsonism (DYT3) and Klinefelter syndrome. The Xp22.31 copy number duplication is of great interest due to its prevalence and that in males it's often associated with intellectual disability, autism and seizures, but has never been described presenting with tremor.

Design/Methods DESIGN/METHODS: Case report.

Results RESULTS: Our patient presented with lifelong moderate intellectual impairment, mild motor delay and tremor since 5 years of age with progressive worsening in the past 4 years affecting mainly his right arm. Family history was notable for an increased incidence of autism and intellectual disability in the males on the maternal side, with his brother being severely intellectually impaired but without tremor. Examination revealed subtle dysmorphic features, cognitive impairment, mildly increased tone in the arms, and a coarse 2-4 Hz tremor in the arms (right, grade 3; left, grade 1) most prominent at rest but also seen anti-gravity. MRI brain showed pachygyria most prominent in the precentral gyri. Detailed genetic evaluation showed a 1.6 Mb, previously reported duplication at Xp22.31, which was maternal in origin.

Conclusions CONCLUSIONS: Given the family history of autism and intellectual disability in the males on the maternal side, the X-chromosome abnormality may be causative and/or contributing to his phenotype rather than a benign copy number variant. Genomic instability is a feature of the Xp22.31 region and pathogenicity of this relatively common duplication is a focus of intense research. To our knowledge tremor has never been described as part of the non-distinct phenotype of intellectual disability, seizure and mild dysmorphic features seen with this microduplication.

Authors/Disclosures
Anna Sorokin, MD PRESENTER	No disclosure on file
Anna M. Szekely, MD (Yale University School of Medicine, Department of Neurology)	No disclosure on file
Bahman Jabbari, MD, FAAN	Dr. Jabbari has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Jabbari has received publishing royalties from a publication relating to health care.
Alasdair Coles, MD, PhD (University of Cambridge)	Dr. Coles has nothing to disclose.

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