Diagnostic delay in Parkinson's disease caused by PRKN mutations

Objective: To confirm that there is a diagnostic delay in Parkin-related Parkinson Disease and to explore possible factors causing such a delay. Methods: We retrospectively analyzed our patients with mutations in the parkin RBR E3 ubiquitin protein ligase gene (PRKN). We collected a total of 34 patients and focused on 18 cases (14 homozygous, 4 compound heterozygous). An arbitrary cut-off of 10 years from disease onset to diagnosis was considered to define patients with delayed diagnosis. Results: Eight of 18 cases had a significant delay in their diagnosis (25.3 +/- 17 years). By comparing patients with and without a delayed diagnosis and subsequently, comparing these groups to a group of young onset PD negative for mutations of PRKN, SNCA, DJ1, PINK1, LRRK2, GBA, and ATP13A2, we identified a specific phenotype associated with a diagnostic delay: young age, lack of tremor, and involvement of lower limbs (particularly dystonia affecting gait) at the time of disease onset. Conclusions: Our findings emphasize the diverse phenotypes associated with PRKN mutations and the related diagnostic challenges they present.