Hereditary parkinsonism: Parkinson disease look-alikes--an algorithm for clinicians to "PARK" genes and beyond

Mov Disord. 2009 Oct 30;24(14):2042-58. doi: 10.1002/mds.22675.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Algorithms
  • Environment
  • Heterozygote
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Mutation / physiology
  • Neurodegenerative Diseases / classification
  • Neurodegenerative Diseases / genetics
  • Oncogene Proteins
  • Parkinson Disease / classification
  • Parkinson Disease / epidemiology
  • Parkinson Disease / etiology
  • Parkinson Disease / genetics*
  • Protein Deglycase DJ-1
  • Ubiquitin-Protein Ligases / genetics*

Substances

  • Intracellular Signaling Peptides and Proteins
  • Oncogene Proteins
  • Ubiquitin-Protein Ligases
  • parkin protein
  • PARK7 protein, human
  • Protein Deglycase DJ-1