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: 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: 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: 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: Schizophrenia is associated with impairment in multiple cognitive domains. There is a paucity of research on the effect of prolonged illness duration (≥ 15 years) on cognitive performance along multiple domains. In this pilot study, we used the Global Neuropsychological Assessment (GNA), a brief cognitive battery, to explore the patterns of cognitive impairment in recent-onset (≤ 2 years) compared to chronic schizophrenia (≥ 15 years), and correlate cognitive performance with brain morphometry in patients and healthy adults. Methods: We assessed cognitive performance in patients with recent-onset (n = 17, illness duration ≤ 2 years) and chronic schizophrenia (n = 14, duration ≥ 15 years), and healthy adults (n = 16) using the GNA and examined correlations between cognitive scores and gray matter volumes computed from T1-weighted magnetic resonance imaging images. Results: We observed cognitive deficits affecting multiple domains in the schizophrenia samples. Selectively greater impairment of perceptual comparison speed was found in adults with chronic schizophrenia (p = 0.009, η2partial = 0.25).In the full sample (n = 47), perceptual comparison speed correlated significantly with gray matter volumes in the anterior and medial temporal lobes (TFCE, FWE p ＜ 0.01). Conclusion Along with generalized deficit across multiple cognitive domains, selectively greater impairment of perceptual comparison speed appears to characterize chronic schizophrenia. This pattern might indicate an accelerated or premature cognitive aging. Anterior-medial temporal gray matter volumes especially of the left hemisphere might underlie the impairment noted in this domain in schizophrenia.

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.