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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 …
Contributors All persons who meet authorship criteria are listed as authors, and all authors certify that they have participated sufficiently in the work to take public responsibility for the content, including participation in the concept, design, analysis, writing or revision of the manuscript. Furthermore, each author certifies that this material or similar material has not been and will not be submitted to or published in any other publication before its appearance in the Journal of Neurology, Neurosurgery and Psychiatry. Author roles: 1. Research Project: A. Conception, B. Organization, C. Execution; 2. Statistical Analysis: A. Design, B. Execution, C. Review and Critique; 3. Manuscript Preparation: A. Writing the First Draft, B. Review and Critique. MW: 1C, 2A, 2B, 2C, 3A, 3B. SSM: 1C, 2C, 3B. DC: 3B. KS: 3B. LC: 3B. PS: 3B. TC: 3B. JM: 3B. MOR: 3B. RS: 3B. JS: 3B. PGS: 1C, 3B. JPL: 1C, 3B. RCD: 1C, 3B. SM: 1C, 2C, 3B. All persons who have made substantial contributions to the work reported in the manuscript (eg, technical help, writing and editing assistance, general support), but who do not meet the criteria for authorship, are named in the Acknowledgements section. If we have not included an acknowledgement, then that indicates we have not received substantial contributions from non-authors.
Funding Funding for the project was provided by the Wellcome Trust.
Competing interests None declared.
Patient consent Obtained.
Ethics approval Ethics comittee LCCH.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement All additional unpublished data from the study will be provided as supplemental material, so it can be accessed with the publication.
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