Genetic anticipation in Parkinson's disease

We studied age at onset and family history of 137 patients (probands) with the diagnosis of idiopathic Parkinson's disease (PD). Probands (N = 21) who had an affected parent, aunt, or uncle were younger (p = 0.0001) at the onset of PD (47.7 +/- 8.8 years) than were probands (N = 11) who had an affected sib only (60.3 +/- 12.9 years) and probands (N = 105) who had no affected sib, parent, aunt, or uncle (59.2 +/- 11.4 years). Age at onset of affected family members differed significantly between generations (p = 0.0001). Age at onset was earlier, by an average of 17 years, in the proband generation than in the parental generation. The intrafamily variation in the calendar year of onset was too great to suggest a common point of exposure. Our data are most compatible with genetic anticipation, which could suggest involvement of an unstable trinucleotide repeat.