Antipsychotic-induced extrapyramidal symptoms (EPS) significantly impact patient adherence and treatment outcomes in schizophrenia. While genetic susceptibility to EPS has been recognized, rare mutations influencing dopamine regulation remain underexplored. We report a case of a 43-year-old woman with atypical psychosis who developed severe EPS following olanzapine treatment, despite its lower propensity. Genetic testing revealed a heterozygous duplication in the PRKRA gene, a key regulator of stress response pathways and movement control. This finding underscores the role of individualized pharmacogenomics in optimizing care. Additionally, allopurinol augmentation in this case suggests a novel therapeutic approach for neuroleptic sensitivity, leveraging its antioxidative and neuroprotective properties.

The CLC family of chloride channels and transporters plays crucial roles in endosomal/lysosomal function, with dysfunction contributing to protein aggregation and dementia development. CLCN6 mutations are recognized in early-onset neurodegenerative disorders, but reports from India remain limited. We report the first case from India of frontotemporal dementia associated with a novel CLCN6 mutation. A 56-year-old woman presented with rapidly progressive behavioral changes, cognitive decline, and frontotemporal atrophy. Genetic testing revealed a novel heterozygous missense variant c.1615A>G (p.Ser539Gly) in exon 16 of the CLCN6 gene. Comprehensive evaluation excluded autoimmune encephalopathy, and the patient showed partial response to symptomatic treatment. This case expands the geographical and phenotypic spectrum of CLCN6-associated neurodegeneration and highlights the importance of genetic testing in early-onset dementia.

Mutations in the NKX2-1 gene cause a syndromic disorder affecting the brain, thyroid, and lungs. There are few case reports in the literature discussing the association between NKX2-1 gene mutation and neurodevelopmental disorders. In this case report, a 12-year-old girl with an NKX2-1 gene mutation, articulation disorder, and specific learning disorder is presented. This report discusses the potential neurodevelopmental risks associated with NKX2-1 mutations. Future research may further clarify the potential co-occurrence of these conditions, contributing to a more comprehensive understanding of the syndrome's components.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition frequently complicated by severe self-injurious behavior (SIB), which may be particularly challenging in children with rare genetic syndromes such as Helsmoortel-van der Aa syndrome. We describe a 10-year-old nonverbal girl with ASD and Helsmoortel-van der Aa syndrome who presented with chronic, severe SIB resulting in ocular rupture. Previous trials with multiple antipsychotics and benzodiazepines provided limited benefit. Following the introduction of naltrexone, the frequency and severity of SIB declined by more than 50% within 4 weeks, accompanied by improvements in irritability and sleep and no reported adverse effects. Clinical ratings supported this response, with Clinical Global Impression-Severity decreasing from 7 to 4 and Clinical Global Impression-Improvement rated as 2. This case suggests that naltrexone may be a useful adjunctive option for treatment-resistant SIB and warrants further systematic investigation.

Schizophrenia is a chronic mental disorder characterized by abnormal synaptic connectivity. N-methyl- D -aspartate receptors (NMDARs) are essential for synaptic transmission and plasticity, and rare variants in the genes encoding NMDARs are linked to neurodevelopmental disorders. In this study, we examined rare pathogenic mutations in four GRIN2 genes, which encode the NMDAR subunit 2, in patients with schizophrenia using ion semiconductor technology and PCR-based fluorescence-based cycle sequencing. We identified 10 novel ultra-rare missense mutations in the GRIN2 genes, none of which were found in the GnomAD_genomes and the Taiwan BioBank. These findings suggest that ultra-rare pathogenic mutations may be present in some individuals with schizophrenia, supporting the existence of rare coding variants of synapse-associated genes that contribute to the genetic architecture of schizophrenia. Future research should explore the in-vitro and in-vivo effects of the identified mutations on the pathophysiology of schizophrenia for further insights.