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GNAO1-related neurodevelopmental disorder: Literature review and caregiver survey

ABSTRACT: Highlights • Current genotype-phenotype correlations in GNAO1 disorders are insufficiently understood.• In a novel series of 15 patients, reported epilepsy phenotype and medication response is highly variable.• A review of the literature shows GNAO1-related neurodevelopmental disorders to be heterogeneous with variable manifestations of hypotonia (91%), movement disorders (89%), and epilepsy (53%).

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.

SUBMITTER: JoJo Yang Q

PROVIDER: S-EPMC9841045 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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