GNAO1-related neurodevelopmental disorder: Literature review and caregiver survey

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 devel-opmental 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.(c) 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

This study investigated GNAO1-related neurodevelopmental disorder through an online survey and literature review. The survey results showed a high correlation between GNAO1 variants and epilepsy, with varying efficacy of anti-seizure medications. The literature review revealed an epilepsy prevalence of approximately 53% in GNAO1-related cases, with 36% having developmental and epileptic encephalopathy.