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.

DNA sequence, GRN protein, LRRK2 protein, MAPT protein, adult, aged, article, brain, case control study, controlled study, dementia, disease transmission, family, family history, female, gene mutation, gene sequence, genetic analysis, genetic predisposition, genetics, histopathology, human, major clinical study, male, metabolism, parkinsonism, pathology, pedigree, phenotype, priority journal, progressive supranuclear palsy, protein serine threonine kinase, risk, signal peptide, tau protein, tauopathy, tremor,
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