GNAO1 encephalopathy: clinical features

Genetics and pathology

• This is caused by mutations in the GNAO1 gene on chromosome 16
• The gene encodes the Gαo subunit of G proteins
• The mutation disrupts the G-protein cAMP pathway axis
• The mutations may increase the risk of ependymomas and glioblastomas
• The mildest phenotypes are associated with variants affecting the C-terminal region

References

1. Danti FR, Galosi S, Romani M, et al.GNAO1 encephalopathy: Broadening the phenotype and evaluating treatment and outcome. Neurol Genet 2017; 3:e143. 
2. Arya R, Spaeth C, Gilbert DL, Leach JL, Holland KD. GNAO1-associated epileptic encephalopathy and movement disorders: c.607G>A variant represents a probable mutation hotspot with a distinct phenotype. Epileptic Disord 2017; 19:67-75.
3. Saitsu H, Fukai R, Ben-Zeev B, et al. Phenotypic spectrum of GNAO1 variants: epileptic encephalopathy to involuntary movements with severe developmental delay. Eur J Hum Genet 2016; 24:129-134.
4. 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; 93:496-505.
5. Kelly M, Park M, Mihalek I, et al. Spectrum of neurodevelopmental disease associated with the GNAO1 guanosine triphosphate-binding region. Epilepsia 2019; 60:406-418. 
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Related checklists

• GNAO1 encephalopathy: differential diagnosis
• GNAO1 encephalopathy: management