title: Parkin disease: a phenotypic study of a large case series.
abstract: Mutations in the parkin gene, PARK2, are a common cause of parkinsonism in familial as well as isolated cases with an age of onset <40 years and should be considered in the diagnostic work up of young-onset parkinsonism. We report a detailed clinical evaluation of a personal series of 24 patients with mutations in the parkin gene. The clinical presentation of most cases was broadly comparable to that of previous descriptions of autosomal recessive early-onset or juvenile parkinsonism and young-onset Parkinson's disease and also had similarities with phenotypes of dopa-responsive dystonia. However, our only case with consanguineous parents had an age of onset of 54 years. We report three new phenotypes at presentation: cervical dystonia; autonomic dysfunction and peripheral neuropathy; and pure exercise-induced dystonia. We emphasize a number of clinical features that can be seen in parkin disease: focal dystonia; early instability; freezing; festination or retropulsion; concurrent autonomic failure; dramatic response to anticholinergics; early or atypical L-dopa-induced dyskinesias; exquisite sensitivity to small doses of L-dopa; and recurrent psychosis, even taking L-dopa alone. We also report behavioural disorder prior to the onset of parkinsonism. Some relatives carrying a single parkin mutation without extrapyramidal symptoms or signs also had psychiatric symptoms that might be related to their carrier status.
authors.affiliation: Department of Molecular Pathogenesis, Royal Free Hospital and University College Medical School, London, UK.
authors.forename: Naheed L
authors.initials: NL
authors.lastname: Khan
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Graham
authors.forename: Peter
authors.initials: P
authors.lastname: Critchley
authors.forename: Anette E
authors.initials: AE
authors.lastname: Schrag
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Wood
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lees
authors.forename: Kailash P
authors.initials: KP
authors.lastname: Bhatia
authors.forename: Niall
authors.initials: N
authors.lastname: Quinn
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D001342:Autonomic Nervous System Diseases / Q000235:genetics; D004421:Dystonia / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008025:Ligases / Q000235:genetics*; D008297:Male; D001523:Mental Disorders / Q000209:etiology / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D020734:Parkinsonian Disorders / Q000188:drug therapy / Q000235:genetics* / Q000523:psychology; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D044767:Ubiquitin-Protein Ligases
chemical_list: D007980:Levodopa; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D008025:Ligases