Objective: To describe the clinical presentation, diagnostic evaluation, and genetic findings in a 7-year-old male with a hyperkinetic movement disorder associated with a novel GNAI1 variant, expanding the phenotypic spectrum of GNAI1-related disorders.

Background: Pathogenic variants in genes, such as GNAO1, encoding G-protein coupled receptor (GPCR) associated proteins have been linked to broad phenotypes encompassing hyperkinetic movement disorders, epilepsy, and intellectual disability (ID). GPCRs are involved in post-synaptic signaling modulation and cyclic adenosine monophosphate (cAMP) metabolism. GNAI1 encodes the GPCR-associated alpha-i1 subunit (Gα1) and has been described in cases with ID and epilepsy but has not previously been reported in association with movement disorders.

Method: We performed detailed clinical characterization, neuroimaging, electroencephalography (EEG), and whole genome sequencing in a 7-year-old boy presenting with a complex hyperkinetic movement disorder.

Results: We describe a 7-year-old boy with history of prematurity and in utero substance exposure who presented with a complex hyperkinetic movement disorder characterized by dystonia, myoclonus, and paroxysmal dyskinesias. The most disabling feature was a myoclonic tremor, which significantly impaired his ability to use eating and writing utensils. Paroxysmal dyskinetic movements triggered by running contributed to falls. Interictal dystonia was mild. Brain magnetic resonance imaging showed white matter abnormalities associated with prematurity. Prolonged EEG monitoring was unremarkable. Whole genome sequencing identified a likely pathogenic GNAI1 variant (c.64A>T). Disabling myoclonic tremor responded to clonazepam treatment.

Conclusion: This case report expands the phenotypic spectrum of GNAI1-related disorders to include paroxysmal and chronic hyperkinetic movement disorders. The findings suggest that GNAI1 should be considered alongside other GPCR-related disorders in the differential diagnosis of childhood-onset complex hyperkinetic movement disorders associated with ID, particularly when myoclonic tremor is a prominent feature. Recognition of this association may facilitate diagnosis and guide therapeutic interventions.

« Back to 2025 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/gnai1-associated-childhood-onset-hyperkinetic-movement-disorder-a-case-report/