The Influence of Genetics in the Early Development of Axial Postural Abnormalities in Parkinson's Disease

Background; Postural abnormalities (PA) can complicate Parkinson's disease (PD). While age and motor severity are established predictors, the genetic role remains underexplored. Objective: To evaluate the influence of major genetic variants on PA development in PD over 4 years. Methods: We analyzed 429 patients from Parkinson's Progression Markers Initiative, including GBA, LRRK2 and SNCA mutation carriers. PA were assessed using the MDS-UPDRS-III item 3.13 and risk factors were analyzed with Cox uncertain regression. Results: SNCA-PD patients were the youngest at onset (50.8 years) and showed the highest PA cumulative incidence over 4 years (30%), followed by GBA-PD (25.8%), idiopathic PD (23%), and LRRK2-PD (17.2%). No significant differences in PA prevalence were found across groups at baseline or at the 4-year follow-up, and genetic status was not a predictor for PA development. Results: SNCA-PD patients were the youngest at onset (50.8 years) and showed the highest PA cumulative incidence over 4 years (30%), followed by GBA-PD (25.8%), idiopathic PD (23%), and LRRK2-PD (17.2%). No significant differences in PA prevalence were found across groups at baseline or at the 4-year follow-up, and genetic status was not a predictor for PA development. Conclusions: Although not significant, the higher PA incidence in SNCA-PD, despite its younger age, suggests that genetic factors may influence PA progression, warranting further studies.