BACKGROUND: Progressive supranuclear palsy (PSP) is a progressive neurodegenerative disorder characterized by aggregates of the microtubule-associated protein tau (MAPT). A nonsignificant trend for positive family history has been observed in two case-control studies and several pedigrees with familial clustering of parkinsonism have been described. Occasionally, mutations in MAPT are found in patients with a clinical phenotype similar to PSP. In this case-control study, we compared the occurrence of dementia and parkinsonism among first-degree relatives of patients with PSP with an age- and sex-matched control group. METHODS: Family history of dementia and parkinsonism was collected from all first-degree relatives of patients with PSP who fulfilled the international National Institute of Neurological Disorders and Stroke criteria for PSP. Age- and sex-matched controls were selected from the Rotterdam Study. Genetic testing and pathologic examination was performed in a subset of familial PSP cases. RESULTS: Fifty-seven (33%) of the 172 patients with PSP had at least one first-degree relative who had dementia or parkinsonism compared to 131 (25%) of the control subjects (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.01-2.13). In patients with PSP, more first-degree relatives with parkinsonism were observed compared to controls, with an OR 3.9 (95% CI 1.99-7.61). Twelve patients with PSP (7%) fulfilled the criteria for an autosomal dominant mode of transmission. The intrafamilial phenotype within these pedigrees varied among PSP, dementia, tremor, and parkinsonism. Genetic studies revealed one patient with a P301L mutation in MAPT. Pathologic examination of five familial cases confirmed the clinical diagnosis of PSP, with predominant four repeat tau pathology in affected brain areas. CONCLUSION: This study demonstrates familial aggregation of parkinsonism in progressive supranuclear palsy.

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doi.org/10.1212/WNL.0b013e3181a92bcc, hdl.handle.net/1765/17137
Neurology
Erasmus MC: University Medical Center Rotterdam

Donker Kaat, L, Boon, A.J.W, Azmani, A, Kamphorst, W, Breteler, M.M.B, Anar, B, … van Swieten, J.C. (2009). Familial aggregation of parkinsonism in progressive supranuclear palsy. Neurology, 73(2), 98–105. doi:10.1212/WNL.0b013e3181a92bcc