The genetic and clinico-pathological profile of early-onset progressive supranuclear palsy (2019)

Type of publication:
Journal article

Jabbari E.; Woodside J.; Tan M.M.X.; Morris H.R.; 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.

Movement Disorders; Sep 2019; vol. 34 (no. 9); p. 1307-1314

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).
Method(s): 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.
Result(s): 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).
Conclusion(s): 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.

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