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. 2019 Sep;34(9):1307-1314.
doi: 10.1002/mds.27786. Epub 2019 Jul 12.

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

Edwin Jabbari  1   2 , John Woodside  1   2 , Manuela M X Tan  1   2 , Nicola Pavese  3 , Oliver Bandmann  4 , Boyd C P Ghosh  5 , Luke A Massey  6 , Erica Capps  7 , Tom T Warner  8   9 , Andrew J Lees  8   9 , Tamas Revesz  8   9 , Janice L Holton  8   9 , Nigel M Williams  10 , Donald G Grosset  11 , Huw R Morris  1   2
Affiliations

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

Edwin Jabbari et al. Mov Disord. 2019 Sep.

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.

Keywords: Parkinson's disease/parkinsonism; clinical neurology; genetics; progressive supranuclear palsy.

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Figures

Figure 1
Figure 1
Initial (A) and final/current (B) clinical profiles of EOPSP, LOPSP, and PD. Radar charts comparing the percentage (%) of EOPSP, LOPSP, and PD cases with Movement Disorder Society PSP diagnostic criteria clinical features in early (A) and late (B) stages of disease. EOPSP, early‐onset PSP; LOPSP, late‐onset PSP; PD, Parkinson's disease; PSP, progressive supranuclear palsy.
See this image and copyright information in PMC

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