This case report describes a 17-year-old girl with a POGZ gene mutation who developed malignant catatonia — a severe, life-threatening neuropsychiatric condition involving psychomotor impairment, mutism, and autonomic instability. Whole-exome sequencing identified a heterozygous POGZ variant, suggesting the mutation contributed to her neurological vulnerability rather than directly causing the condition. Electroconvulsive therapy provided temporary improvement, but her course was complex and required a multidisciplinary approach. The case highlights the importance of genetic investigation in treatment-resistant, complex neuropsychiatric presentations in adolescents.