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Understanding the Anatomy of Dystonia: Determinants of Penetrance and Phenotype

  • Neuroimaging (DJ Brooks, Section Editor)
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Abstract

The dystonias comprise a group of syndromes characterized by prolonged involuntary muscle contractions resulting in repetitive movements and abnormal postures. Primary dystonia has been associated with over 14 different genotypes, most of which follow an autosomal dominant inheritance pattern with reduced penetrance. Independent of etiology, the disease is characterized by extensive variability in disease phenotype and clinical severity. Recent neuroimaging studies investigating this phenomenon in manifesting and non-manifesting genetic carriers of dystonia have discovered microstructural integrity differences in the cerebello-thalamo-cortical tract in both groups related to disease penetrance. Further study suggests these differences to be specific to subrolandic white matter regions somatotopically related to clinical phenotype. Clinical severity was correlated to the degree of microstructural change. These findings suggest a mechanism for the penetrance and clinical variability observed in dystonia and may represent a novel therapeutic target for patients with refractory limb symptoms.

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Acknowledgment

David Eidelberg has received grant support from the National Institute of Neurological Disorders and Stroke (R01 NS 072514), The Bachmann-Strauss Dystonia and Parkinson Foundation, High Q Foundation, and the Dana Foundation.

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Conflict of Interest

Renata Lerner has received an MD/PhD candidate stipend from Hofstra North Shore-LIJ School of Medicine. Martin Niethammer is employed by The Feinstein Institute for Medical Research. David Eidelberg has board membership with The Bachmann-Strauss Dystonia and Parkinson Foundation, Michael J. Fox Foundation for Parkinson’s Research, Thomas Hartman Foundation for Parkinson’s Research, Inc.; has been a consultant for Pfizer, Inc.; and is employed by The Feinstein Institute for Medical Research. He is coinventor of patents re: Markers for use in screening patients for nervous system dysfunction and a method and apparatus for using same; no financial gain. He has received honoraria from The Bachmann-Strauss Dystonia and Parkinson Foundation and Michael J. Fox Foundation for Parkinson’s Research.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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  1. Center for Neurosciences, The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY, 11030, USA

    Renata P. Lerner, Martin Niethammer & David Eidelberg

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  1. Renata P. Lerner
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Correspondence to David Eidelberg.

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Lerner, R.P., Niethammer, M. & Eidelberg, D. Understanding the Anatomy of Dystonia: Determinants of Penetrance and Phenotype. Curr Neurol Neurosci Rep 13, 401 (2013). https://doi.org/10.1007/s11910-013-0401-0

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