Parkin Pleiotropy: Extremely Atypical Phenotypes in Patients With Compound Heterozygous Mutations

Abstract

Background: Parkin mutations are suspected in early-onset Parkinson's disease with early motor complications, and in pedigrees showing an autosomal recessive pattern. Some compound heterozygous mutations can present with various uncommon phenotypes.

Case report: Two siblings with the same mutations, one with atypical postural and action tremor, and the other with an axonal motor autonomic neuropathy. A woman with a 45-year history of slowly progressive parkinsonism with no motor complications.

Discussion: Due to the variability of phenotypes of Parkin mutations, testing should also be warranted in patients with atypical tremor syndromes or axonal polyneuropathy when more common causes have been ruled out.

Highlights: We report three patients with extremely atypical parkin mutation phenotypes: an atypical tremor syndrome, an axonal motor autonomic neuropathy, and a remarkably slowly progressive parkinsonism. This shows that parkin mutations may present with a highly variable phenotype, and should be considered in patients with such manifestations.