GNAO1-related neurodevelopmental disorder: Literature review and caregiver survey

Qian-Zhou JoJo Yang; Brenda E Porter; Erika T Axeen

doi:10.1016/j.ebr.2022.100582

GNAO1-related neurodevelopmental disorder: Literature review and caregiver survey

Epilepsy Behav Rep. 2022 Dec 31:21:100582. doi: 10.1016/j.ebr.2022.100582. eCollection 2023.

Authors

Qian-Zhou JoJo Yang¹, Brenda E Porter², Erika T Axeen³

Affiliations

¹ Division of Child Neurology, Department of Neurology, University of North Carolina, Chapel Hill, NC, United States.
² Division of Child Neurology, Department of Neurology, Stanford University, Palo Alto, CA, United States.
³ Division of Pediatric Neurology, Department of Neurology, University of Virginia, United States.

Abstract

Background: GNAO1-related neurodevelopmental disorder is a heterogeneous condition characterized by hypotonia, developmental delay, epilepsy, and movement disorder. This study aims to better understand the spectrum of epilepsy associated with GNAO1 variants and experience with anti-seizure medications, and to review published epilepsy phenotypes in GNAO1.

Methods: An online survey was distributed to caregivers of individuals diagnosed with GNAO1 pathogenic variants, and a literature review was conducted.

Results: Fifteen respondents completed the survey with the median age of 39 months, including a novel variant p.Q52P. Nine had epilepsy - six had onset in the first week of life, three in the first year of life - but two reported no ongoing seizures. Seizure types varied. Individuals were taking a median of 3 seizure medications without a single best treatment. Our cohort was compared to a literature review of epilepsy in GNAO1. In 86 cases, 38 discrete variants were described; epilepsy is reported in 53 % cases, and a developmental and epileptic encephalopathy in 36 %.

Conclusions: While GNAO1-related epilepsy is most often early-onset and severe, seizures may not always be drug resistant or lifelong. Experience with anti-seizure medications is varied. Certain variant "hotspots" may correlate with epilepsy phenotype though genotype-phenotype correlation is poorly understood.

Keywords: ASM, antiseizure medications; DEE, developmental and epileptic encephalopathy; Developmental and epileptic encephalopathy; EEG, electroencephalogram; Epilepsy; GNAO1; GNAO1, G protein subunit alpha o1; GPCR, G protein coupled receptor; Genetic; MRI, magnetic resonance imaging; Movement disorder; Neurodevelopmental disorder; cAMP, cyclic adenosine monophosphate.

Publication types

Case Reports