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 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.