'Familial Parkinson's disease' - A case-control study of families

Background: Parkinson's disease (PD) patients frequently report a family history of PD and this may provide etiological clues to PD. It has also been suggested that a report of a negative family history is reliable. We studied the prevalence of PD in relatives of PD patients to assess the reliability of family history and to evaluate possible explanations of 'familial PD'(fPD). Methods: 81 of 650 (12.5%) PD probands (all PD patients seen at clinic in 4 years) reported a positive family history of PD. Each fPD proband was matched with non-familial PD (nfPD) proband by gender and year of birth. Screening and follow-up questionnaires were mailed to relatives to obtain information concerning pedigree and presence of neurodegenerative disease. Available family members (regardless of disease status) were examined. Results: On examination, 8 persons, said to be 'normal' by probands, relatives and themselves, had definite or possible PD (5 fPD, 3 nfPD). The prevalence rate of PD among first and second degree living relatives of probands varied significantly between fPD and nfPD groups (6269/100 000 versus 1190/100 000; p < 0.001). The weighted prevalence (taking into account the proportions of fPD and nfPD within the clinic) was 1822/100 000, a value more than 5 times higher than reported prevalence rates of PD in the general population (p < 0.001). The prevalence rate was greater in first degree relatives than second degree. Conclusions: 'Familial parkinsonism' cannot be explained merely by size of or advanced age within families. Significant numbers of previously unrecognized PD patients may be identified despite a 'negative' family history. That is, the patient's report of an absence of familial parkinsonism is frequently inaccurate. The prevalence rate in relatives of PD patients appears to be higher than the general population regardless of the family history reported by a PD patient. We believe our study suggests that genetic influences or early life environmental exposures are likely to be of etiological importance in PD.