The genetic and clinico-pathological profile of early-onset progressive supranuclear palsy

Jabbari, E. et al. (2019) The genetic and clinico-pathological profile of early-onset progressive supranuclear palsy. Movement Disorders, 34(9), pp. 1307-1314. (doi: 10.1002/mds.27786) (PMID:31299107) (PMCID:PMC6790973)

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Background: Studies on early‐onset presentations of progressive supranuclear palsy (PSP) have been limited to those where a rare monogenic cause has been identified. Here, we have defined early‐onset PSP (EOPSP) and investigated its genetic and clinico‐pathological profile in comparison with late‐onset PSP (LOPSP) and Parkinson's disease (PD). Methods: We included subjects from the Queen Square Brain Bank, PROSPECT‐UK study, and Tracking Parkinson's study. Group comparisons of data were made using Welch's t‐test and Kruskal‐Wallis analysis of variance. EOPSP was defined as the youngest decile of motor age at onset (≤55 years) in the Queen Square Brain Bank PSP case series. Results: We identified 33 EOPSP, 328 LOPSP, and 2000 PD subjects. The early clinical features of EOPSP usually involve limb parkinsonism and gait freezing, with 50% of cases initially misdiagnosed as having PD. We found that an initial clinical diagnosis of EOPSP had lower diagnostic sensitivity (33%) and positive predictive value (38%) in comparison with LOPSP (80% and 76%) using a postmortem diagnosis of PSP as the gold standard. 3/33 (9%) of the EOPSP group had an underlying monogenic cause. Using a PSP genetic risk score (GRS), we showed that the genetic risk burden in the EOPSP (mean z‐score, 0.59) and LOPSP (mean z‐score, 0.48) groups was significantly higher (P < 0.05) when compared with the PD group (mean z‐score, −0.08). Conclusions: The initial clinical profile of EOPSP is often PD‐like. At the group level, a PSP GRS was able to differentiate EOPSP from PD, and this may be helpful in future diagnostic algorithms.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Grosset, Dr Donald
Authors: Jabbari, E., Woodside, J., Tan, M. M.X., Pavese, N., Bandmann, O., Ghosh, B. C.P., Massey, L. A., Capps, E., Warner, T. T., Lees, A. J., Revesz, T., Holton, J. L., Williams, N. M., Grosset, D. G., and Morris, H. R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:Movement Disorders
ISSN (Online):1531-8257
Published Online:12 July 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Movement Disorders 34(9): 1307-1314
Publisher Policy:Reproduced under a Creative Commons License

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