We report a case of GNB1 encephalopathy arising from a de novo mutation in an uncommon locus presenting with a unique phenotype consisting of dystonia with myoclonus and vertical supranuclear gaze palsy (VSGP).

This 27-year-old female presented with hypotonia and global developmental delay, intellectual disability, short stature, low body weight, dysarthria, a wide-based gait, and dystonia. She only had partial improvement with a trial of amantadine, and did not respond to dopaminergic therapy. In the ensuing years, she developed myoclonus, which persisted despite a gradual tapering off of amantadine. At 12 years of age, further examination disclosed a VSGP. Her axial dystonia, posture, and gait significantly improved with botulinum toxin (BoNTA) injections to the paraspinal muscles beginning at 18 years of age.

Investigations including blood work, CSF neurotransmitters, imaging, and metabolic parameters were unrevealing. Electrophysiologic testing were consistent for both myoclonus superimposed on dystonia. Initial genetic investigations, which also included a proband whole exome sequencing (WES) were nondiagnostic. Updated trio WES six years after identified a de novo, heterozygous missense, likely pathogenic variant in the GNB1 gene (c.1009A>C (p.Lys337Gln); exon 11).