1. The genetic and clinico-pathological profile of early-onset progressive supranuclear palsy.
- Author
-
Jabbari, Edwin, Woodside, John, Tan, Manuela, Pavese, Nicola, Bandmann, Oliver, Ghosh, Boyd, Massey, Luke, Capps, Erica, Warner, Tom, Lees, Andrew, Revesz, Tamas, Holton, Janice, Williams, Nigel, Grosset, Donald, and Morris, Huw
- Subjects
Parkinsons disease/parkinsonism ,clinical neurology ,genetics ,progressive supranuclear palsy ,Adult ,Age of Onset ,Aged ,Aged ,80 and over ,Diagnosis ,Differential ,Disease Progression ,Female ,Gait Disorders ,Neurologic ,Genetic Testing ,Genotype ,Humans ,Male ,Middle Aged ,Parkinson Disease ,Predictive Value of Tests ,Supranuclear Palsy ,Progressive ,Tissue Banks ,Young Adult - 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 Parkinsons disease (PD). METHODS: We included subjects from the Queen Square Brain Bank, PROSPECT-UK study, and Tracking Parkinsons study. Group comparisons of data were made using Welchs 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
- Published
- 2019