Hereditary parkinsonism: Parkinson disease look-alikes—An algorithm for clinicians to “PARK” genes and beyond

Authors

  • Christine Klein MD,

    Corresponding author
    1. Department of Neurology, University of Lübeck, Lübeck, Germany
    2. Department of Neurology, Morton and Gloria Shulman Movement Disorders Center, Toronto Western Hospital, Toronto, Canada
    • Department of Neurology, University of Lübeck, Ratzeburger Allee 160, Lübeck 23538, Germany
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  • Susanne A. Schneider MD, PhD,

    1. Department of Neurology, University of Lübeck, Lübeck, Germany
    2. Sobell Department of Motor Neuroscience and Movement Disorders, UCL, Institute of Neurology, Queen Square, London, England
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  • Anthony E. Lang MD, FRCPC

    1. Department of Neurology, Morton and Gloria Shulman Movement Disorders Center, Toronto Western Hospital, Toronto, Canada
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  • Potential conflict of interest: CK was supported by Volkswagen Foundation, Hermann and Lilly Schilling Foundation, Deutsche Forschungsgemeinschaft DFG; SAS was supported by the Brain Research Trust, UK, a grant by the University Lübeck and the Novartis Foundation for Therapeutic Research. AEL: Grants: Canadian Institutes of Health Research, Dystonia Medical Research Foundation, Michael J. Fox Foundation, National Parkinson Foundation, Ontario Problem Gambling Reseach Centre, Parkinson's Disease Foundation, Taro.

  • This article is part of the journal's online CME program. The CME activity including form, can be found online at http://www.movementdisorders.org/education/journalcme/

Abstract

In the past decade, a number of genetic causes of parkinsonism have been identified. As a consequence, clinicians have to consider an increasing range of differential diagnoses when confronted with a patient with parkinsonism with a positive family history. While well-established monogenic forms with PARK acronyms have been reviewed extensively, less emphasis has been placed on other inherited conditions that may also present with signs of parkinsonism or even mimic idiopathic Parkinson's disease clinically. In this review, we focus on three different scenarios in patients with an overall early age of onset of parkinsonism: (i) atypical features in patients with mutations in one of the “PARK” genes; (ii) classical parkinsonism due to mutations in “other than-PARK” genes or yet other genes where parkinsonism may be a well-recognized, concomitant, or even an isolated feature; (iii) atypical parkinsonism in other genetic disorders which are, however, typically characterized by features other than parkinsonism. Atypical features in patients from Group I include, for example, a slower disease course (PARK2, PARK6, PARK7) or dementia (PARK1/4, PARK14). Conditions in Group II have been designated by a DYT or SCA acronym (for example, DYT5 or SCA3) and also include patients with heterozygous GBA mutations, mitochondrial gene mutations. Group III comprises mutations in the FMR1, MAPT, GRN, ATP7B, PANK2, FBXO7, CHAC, FTL1, Huntingtin, JPH3 genes, and a number of even rarer, miscellaneous conditions. © 2009 Movement Disorder Society

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