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



Jabbari, Edwin ORCID: 0000-0001-6844-882X, Woodside, John, Tan, Manuela MX, Pavese, Nicola ORCID: 0000-0002-6801-6194, Bandmann, Oliver, Ghosh, Boyd CP, Massey, Luke A, Capps, Erica, Warner, Tom T ORCID: 0000-0001-6195-6995, Lees, Andrew J ORCID: 0000-0002-2476-4385
et al (show 5 more authors) (2019) The genetic and clinico-pathological profile of early-onset progressive supranuclear palsy. Movement disorders : official journal of the Movement Disorder Society, 34 (9). 1307 - 1314.

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Abstract

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. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Item Type: Article
Depositing User: Symplectic Admin
Date Deposited: 01 Aug 2019 09:09
Last Modified: 28 Nov 2019 01:10
DOI: 10.1002/mds.27786
URI: http://livrepository.liverpool.ac.uk/id/eprint/3050747
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