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For nearly two centuries, investigating the role of heredity in Parkinson disease (PD) has been challenging. Paradoxes abound. Clinical series report that at least 10 to 15% of patients have relatives with PD. Case-control studies report from 2- to 14-fold increased risk of PD if a first-degree relative has the disease.1,2⇓ Yet twin studies do not support a genetic cause of typical PD3 and the known mutations causing parkinsonism are rare.4,5⇓ Which observation is correct? Does PD occur more often in the relatives of patients with PD? Or could the contradictory findings reflect methodologic differences in these studies? In the clinical series and case-control studies, “PD” in relatives was usually determined by interview of the patient with PD or the control. This design is vulnerable to family bias: persons with disease may overestimate and those with no disease underestimate affected relatives.6 In contrast, in studies of families with mutations or of twins, diagnosis was determined by neurologic examination. Could this methodologic difference explain the differences in outcome? Are family history and neurologic examination equally accurate ways to determine PD in relatives? In this issue of Neurology , two articles address this question.
The validity of a family history of PD was assessed in two population-based case-control studies, one by Elbaz et …
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