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.