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.

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.

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.

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.

Objective: aaMutations in the KMT2B gene have been identified in patients previously diagnosed with idiopathic dystonia. Literature on KMT2B-related dystonia is sparse in the Indian and Asian populations. Methods: aaWe report seven patients with KMT2B-related dystonia studied prospectively from May 2021 to September 2022. Patients underwent deep clinical phenotyping and genetic testing by whole-exome sequencing (WES). A systematic literature search was performed to identify the spectrum of previously published KMT2B-related disorders in the Asian subcontinent. Results: aaThe seven identified patients with KMT2B-related dystonia had a median age at onset of four years. The majority experienced onset in the lower limbs (n = 5, 71.4%), with generalization at a median duration of 2 years. All patients except one had complex phenotypes manifesting as facial dysmorphism (n = 4), microcephaly (n = 3), developmental delay (n = 3), and short stature (n = 1). Magnetic resonance imaging (MRI) abnormalities were present in four cases. WES revealed novel mutations in the KMT2B gene in all patients except one. Compared to the largest cohort of patients with KMT2B-related disorders, the Asian cohort, comprising 42 patients, had a lower prevalence of female patients, facial dysmorphism, microcephaly, intellectual disability, and MRI abnormalities. Protein-truncating variants were more prevalent than missense variants. While microcephaly and short stature were more common in patients with missense mutations, facial dysmorphism was more common in patients with truncating variants. Deep brain stimulation, performed in 17 patients, had satisfactory outcomes. Conclusion aaThis is the largest series of patients with KMT2B-related disorders from India, further expanding the clinico-genotypic spectrum. The extended Asian cohort emphasizes the unique attributes of this part of the world.