Clinical profile and Genetic Composition of patients with Juvenile Parkinsonism from a single tertiary care center in India.

Introduction: Studies outlining the genetic architecture of Parkinson's disease in India are sparse, and juvenile parkinsonism is underrepresented in the literature. The objective was to study the clinical, therapeutic, and genetic profile of patients with juvenile parkinsonism and to correlate phenotypic-genotypic characteristics.

Methods: This retrospective chart review was conducted in patients with suspected genetically mediated juvenile parkinsonism (onset≤21 years), who have undergone genetic testing at a tertiary care center in India from 2015-2024. The available phenotypic-genotypic characteristics were evaluated and compared between gene(+) and gene(-) patients.

Results: Forty patients (22 males, 55%) with juvenile parkinsonism were included with mean age at onset and presentation of 15.85±4.96 years and 26.37±10.11 years respectively. The mean duration of illness was 10.43±10.49 years. A positive family history was present in 40% and consanguinity in 45%. Bradykinesia was the most common motor symptom (95%) and cognitive impairment was the commonest non-motor symptom (17.5%). Pathogenic/likely pathogenic variants were identified in 27 patients (67.5 %), with variants in PRKN being the most common (n=8) followed by PLA2G6 (n=7). Gene(+) cases had significantly more severe disease with better levodopa response, more frequent familial consanguinity, oculomotor abnormality, motor fluctuations and dyskinesia. PARK-PLA2G6 patients had significantly more dystonia, gaze restriction, pyramidal signs, severe disease at presentation, with lesser LEDD and motor fluctuations compared to PARK-PRKN patients.

Conclusion: More than two-thirds (67.5%) of the juvenile parkinsonism patients in our cohort had an underlying monogenetic cause. PARK-PRKN, PARK-PLA2G6, and PARK-SYNJ1 are the common causes of genetically mediated juvenile parkinsonism in India.