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GNAO1 (OMIM 139311) encodes a Gα0CNS protein responsible for regulation of GABA-B and α2-receptors, and neurotransmitter release. Mutations of GNAO1 are reported in patients with epileptic encephalopathy (EE) at times with a movement disorder (MD); some display severe hyperkinetic movements without EE, three underwent Deep Brain Stimulation (DBS) with reduction in exacerbations.1–4 (see online supplementary table 3, supporting information (SI)).
We describe the MD phenomenology and course in three patients identified from neurology services in Brisbane and Glasgow with GNAO1-related MD, highlighting effectiveness of DBS in exacerbations.
Informed consent was obtained. Four MD specialists reviewed videos (baseline, exacerbations, post-DBS) using a Proforma (SI) and reached a consensus on movement phenomenology.
All patients had global delay, central hypotonia and MD noted in early life (see online supplementary table 1, patient synopsis, SI). Patient 3 initially showed bradykinesia, rigidity and dystonia; patient 1 resting tremor. All had been diagnosed with dyskinetic Cerebral Palsy (CP), without substantive MRI findings. Medication for baseline MD had variable efficacy (see online supplementary table 2, SI). MRI demonstrated mild progressive atrophy over 6 years in two patients (see online supplementary figure 1, SI). MRI during an exacerbation revealed restricted diffusion in the internal capsules and splenium (corpus callosum) in one (figure 1).
Whole exome sequencing identified de novo heterozygous mutations in the GNAO1 gene in all three patients, confirmed with Sanger sequencing.
Dominant baseline MD varied between patients; agreed features included …
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