Objective: To describe the clinical course, phenomenology, and treatment response in two patients with GNAO1 related movement disorders.

Background: Since the initial report of 4 patients with epileptic encephalopathy by Nakamura et al. in 2013 [1], GNAO1 mutations are increasingly recognized in patients with heterogeneous presentations, primarily comprising epilepsy, developmental delay, and movement disorders [2].

Method: Two patients with GNAO1 mutations are described followed longitudinally from early childhood to young adulthood in a single academic medical center..

Results: Patient 1 is a 25 year old male with de novo GNAO1 mutation c.709G>A with developmental delay, left hemidystonia with generalized choreoathetosis, and episodic altered awareness undergoing workup for seizures versus syncope. Hemi-dystonia was present at birth with subsequent recurrent choreoathetosis beginning early childhood. Multiple medications were trialed before botulinum toxin injection and finally implantation of bilateral GPi DBS at age 11 with significant improvement.

Patient 2 is a 21 year old male with de novo GNAO1 mutation c.625C>T with progressively worsening motor control and speech/swallowing and seizures. Specifically, patient had progressive generalized dystonia with choreoathetosis and paroxysmal ballismus resulting in significant dysphonia/dysphagia and musculoskeletal injuries. Multiple medications were trialed without success before tetrabenazine which was initially effective but required increasingly higher doses. Intrathecal baclofen pump and botulinum toxin injections were also trialed before bilateral GPi DBS implantation at age 20 with improvement in speech and motor control and resolution of ballismus.

Conclusion: GNAO1 mutations underlie heterogeneous phenotypes as illustrated in two longitudinally followed cases here. To our knowledge, there have been fewer than 50 patients in the literature with GNAO1 associated movement disorders described. Our two patients add to the repertoire of this rare genetic disorder with notably fair response to GPi DBS which can be considered early in those with debilitating movement disorders.

References: 1. Nakamura K, Kodera H, Akita T, et al. De Novo mutations in GNAO1, encoding a Gαo subunit of heterotrimeric G proteins, cause epileptic encephalopathy. Am J Hum Genet. 2013 Sep 5;93(3):496-505 2. Schirinzi T, Garone G, Travaglini L, et al. Phenomenology and clinical course of movement disorder in GNAO1 variants: Results from an analytical review. Parkinsonism Relat Disord. 2019 Apr;61:19-25.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/gnao1-related-movement-disorders-2-longitudinally-followed-cases/