GNAO1: description of three distinct cases with the same genotype and literature review

*Correspondence: [e-mail].

Abstract

Case Presentation: Case 1: a previously healthy 1-year-old male, developed global delopmental delay along with dyskinetic tetraparesis and dystonia in the course of 2 years. Electroencephalogram (EEG) was normal, genetic tests presented a pathogenic variant in GNAO1 gene. Case 2: a previously healthy 8-year-old male, started with versive eye seizures at one year old. Later, he developed episodes of upper limb adduction with tonic posturing lasting a few seconds, primarily while sleeping. Brain magnetic ressonance imaging (MRI) showed an ectasia of the lateral ventricles and EEG was compatible with diffuse encephalopathy. Genetic tests presented a pathogenic variant in GNAO1. Case 3: Child 3 years old, female, without complications during pregnancy and birth, evolved with global delay in neuropsychomotor development along with dystonia since she was one year old. EEG showed epileptogenic discharges, and genetic tests also presented a variant in GNAO1.

Discussion: GNAO1 encephalopathy is a rare neurodevelopmental disorder characterized by movement desorders mainly dystonia and early-onset epileptic encephalopathy. GNAO1 encodes Gÿo, the ÿ subunit of Go, which is the most abundant membrane protein in the mammalian central nervous system. It plays important roles in synaptic neurotransmission and neurodevelopment. Comprehensive phenotyping is very important for the diagnosis of these patients, even in the genomic era. It is important to consider the mechanisms underlying movement disorders associated with GNAO1 to rationalize the clinical heterogeneity resulting from different variants, as well as the implications for therapeutic choices. The most common manifestations associated to these variants in GNAO1 are hypotonia, developmental delay, choreoathetosis, epilepsy and dystonia. The literature review demonstrates that movement disorders correspond to 89% of the cases, with comorbid epilepsy in 41% of patients.

Final Comments: The advances in genetic investigations methods improved our diagnostic accuracy. However, understanding the phenotypic heterogeneity is important in the case of conditions with broad presentation in order to treat proeminent symptoms and give families the needed support throughout the disease process. Further literature is needed to improve our knowledge of GNAO1-related presentations.

Publication History

Article published online:
12 May 2025