Marta Ruiz-Lopez1, Maria Eliza Freitas1, Lais M Oliveira1, Renato P Munhoz1, Susan H Fox2, Mohammad Rohani3, Ekaterina Rogaeva4, Anthony E Lang2, Alfonso Fasano5. 1. Edmond J. Safra Program in Parkinson's Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, UHN, Toronto, Ontario, Canada; Division of Neurology, University of Toronto, Toronto, Ontario, Canada. 2. Edmond J. Safra Program in Parkinson's Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, UHN, Toronto, Ontario, Canada; Division of Neurology, University of Toronto, Toronto, Ontario, Canada; Krembil Brain Institute, Toronto, Ontario, Canada. 3. Edmond J. Safra Program in Parkinson's Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, UHN, Toronto, Ontario, Canada; Division of Neurology, University of Toronto, Toronto, Ontario, Canada; Department of Neurology, Hazrat Rasool Hospital, Iran University of Medical Sciences, Tehran, Iran. 4. Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada. 5. Edmond J. Safra Program in Parkinson's Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, UHN, Toronto, Ontario, Canada; Division of Neurology, University of Toronto, Toronto, Ontario, Canada; Krembil Brain Institute, Toronto, Ontario, Canada. Electronic address: alfonso.fasano@uhn.ca.
Abstract
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.
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.
Authors: Mariana L Laporta; S Chandralekha Kruthiventi; Cole D Stang; Emanuele Camerucci; David P Martin; Toby N Weingarten; Andrew C Hanson; Darrell R Schroeder; David O Warner; Rodolfo Savica; Juraj Sprung Journal: Parkinsonism Relat Disord Date: 2021-06-08 Impact factor: 4.402