Objective: 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 profiles of patients with juvenile parkinsonism and to correlate their phenotypic–genotypic characteristics. Methods: This retrospective chart review was conducted in patients with suspected genetically mediated juvenile parkinsonism (onset ≤21 years) who underwent 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, 55.0%) with juvenile parkinsonism were included, with mean ages 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 40.0% of the participants, and consanguinity was present in 45%. Bradykinesia was the most common motor symptom (95.0%), and cognitive impairment was the most common nonmotor symptom (17.5%). Pathogenic/likely pathogenic variants were identified in 27 patients (67.5%), with variants in PRKN being the most common (n=8 patients), followed by those in PLA2G6 (n=7 patients). Gene (+) patients had significantly more severe disease with a better levodopa response and more frequent familial consanguinity, oculomotor abnormalities, motor fluctuations, and dyskinesia. Compared with PARK-PRKN patients, PARK-PLA2G6 patients had significantly more dystonia, gaze restriction, and pyramidal signs and more severe disease at presentation, with a lower levodopa equivalent daily dose and fewer motor fluctuations. Conclusion More than two-thirds (67.5%) of the juvenile parkinsonism patients in our cohort had an underlying monogenic cause. PARK-PRKN, PARK-PLA2G6, and PARK-SYNJ1 are the common causes of genetically mediated juvenile parkinsonism in India.

Objective: Recessive variants in the PINK1 gene are known causes of early-onset Parkinson’s disease (EOPD). To describe the clinical features and genetic profiles of patients with PINK1-related Parkinson’s disease (PARK-PINK1) mutations. Methods: We conducted a retrospective chart review of the demographic, clinical and genetic details of patients from our database carrying biallelic PINK1 variants. Results: A total of 7 patients whose median age at onset was 33 years (range: 20–49) were recruited. All had asymmetrical onset, tremors were present in 4 patients, abnormal posturing was present in 2 patients, and slowness was present in 1 patient. The parkinsonism phenotype was noted in 6 patients (with dystonia in four) and isolated dystonia in one. Among the 6 patients with parkinsonism, five had rest tremors, all had good levodopa responses, and four had motor fluctuations with choreiform dyskinesia. Exome sequencing revealed biallelic pathogenic/likely pathogenic variants, five of which were novel. Conclusion PARK-PINK1 presents as an EOPD with tremor-predominant phenotype, good levodopa-responsiveness, early motor fluctuation and dyskinesia. We describe five novel variants in PINK1 gene.

Objective: In this study, we describe the clinical and investigative profiles of 7 cases of autosomal-recessive spastic ataxia of Charlevoix–Saguenay (ARSACS). Methods: We performed a retrospective chart review of genetically proven cases of ARSACS from our database. Additionally, we reviewed the literature for reported cases of ARSACS from India. Results: All 7 patients experienced disease onset within the first decade of life. According to the available data, all patients had walking difficulty (7/7), spastic ataxia (7/7), classical neuroimaging findings (7/7), sensory‒motor demyelinating polyneuropathy (6/6), abnormal evoked potentials (5/5), and a thickened retinal nerve fiber layer (3/3). Exome sequencing revealed 8 unique pathogenic/likely pathogenic variants (6 novel) in the SACS gene. An additional 21 cases (18 families) of ARSACS that could be identified from India had similar clinical and investigational findings. The most common c.8793delA variant may have a founder effect. Conclusion Our series adds to the previously reported cases of ARSACS from India and expands the genetic spectrum by adding 6 novel variants.