A Novel Variant in GLRA1 Associated With Emotional Stimulus-Sensitive Hemichoreic Movements

We present the case of a 61-year-old woman with late-onset hyperkinetic movement disorder, characterized by involuntary, choreiform movements predominantly affecting the right limbs. Symptoms began at age 60 and were exacerbated by emotional stress. Neurological and neurocognitive evaluations were unremarkable, and extensive diagnostic workup, including Magnetic Resonance Imaging (MRI), Electroencephalogram (EEG), Positron Emission Tomography with Fluorodeoxyglucose (FDG-PET) and genetic testing for common movement disorders, was largely negative. Notably, a heterozygous pathogenic variant (c.736C>T; p.Arg246Trp) in the GLRA1 gene was identified via exome sequencing. This gene encodes a glycine receptor subunit associated with Hyperekplexia (HPX), a rare neurometabolic disorder typically presenting in infancy with exaggerated startle responses. Although our patient did not show a classic HPX phenotype, the clinical picture included emotionally triggered motor symptoms and a positive response to clonazepam, a hallmark of HPX treatment. Clonazepam monotherapy at low doses led to sustained symptom control, while other treatments were less effective. Family history revealed similar late-onset symptoms in the patient's father, though undocumented. This case expands the phenotypic spectrum of HPX and suggests that atypical presentations may be misclassified as functional neurological disorders. It underscores the importance of genetic evaluation in unexplained adult-onset movement disorders and raises the possibility of underrecognized late-onset HPX variants in clinical practice.