Objective: GNAO1 gene mutation is considered in the differential diagnosis of early onset epileptic encephalopathies (EOEE) with movement disorders. De novo GNAO1 mutations were first reported in Ohtahara syndrome and EOEE in four children, associated with abnormal movements in two (1). We present a case of generalized dystonia with de novo GNAO1 gene mutation who presented with development delay (dx at age 11 months) and dystonia onset at the age of 12 and with no history of seizures. There was no response to deep brain stimulation targeting bilateral globus pallidum interna (GPi DBS).

Background: Early onset encephalopathic epilepsy, developmental delay and later development of dyskinetic movement disorders have been reported in the literature as a common phenotype with GNAO1 gene mutation (3).

Method: 27year-old man presented with generalized dystonia. In his early childhood, he was diagnosed with global developmental delay. Between age 4 and 12, he was able to run without assistance but by the age of 12, he started stumbling while walking with in-turning of feet while walking and truncal posturing. He was diagnosed with generalized dystonia at the age of 12. Transient mild improvement was noted with tendon transfer, baclofen and botulinum toxin injections. He neither had a history of seizures or a family history of movement disorders or epilepsy.

Results: MRI brain did not reveal any significant findings. Normal creatinine kinase, alpha fetoprotein levels, chromosome analysis. Whole genome sequence revealed GNAO1 gene mutation: c.724-8G>A, heterozygous de novo, splice mutation.He underwent bilateral GPi DBS at the age of 19 and there was no improvement noted with post-surgery.

Conclusion: Our patient with generalized dystonia without epilepsy, expands the spectrum of GNAO1 gene mutation phenotype. There are only few case reports where DBS was shown to be successful but early intervention was the key, which probably was missed in our case (2). Early onset encephalopathic epilepsy, developmental delay and later development of dyskinetic movement disorders have been reported in the literature as a common phenotype with this gene mutation (3). We propose GNAO1 gene mutation to be considered in not only patients with epileptic encephalopathy, but those that present with isolated movement disorders as well.

References: 1. Nakamura K, Kodera H, Akita T, et al. De Novo mutations in GNAO1, encoding a Galphao subunit of heterotrimeric G proteins, cause epileptic encephalopathy. Am J Hum Genet 2013;93:496–505. 2. Yilmaz, S., Turhan, T., Ceylaner, S. et al. Childs Nerv Syst (2016) 32: 1567. 3. Kulkarni N, Tang S, Bhardwaj R, Bernes S, Grebe TA. Progressive movement disorder in brothers carrying a GNAO1 mutation responsive to deep brain stimulation. J Child Neurol. 2016;31: 211-214.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/gnao1-gene-mutation-generalized-dystonia-without-epilepsy/