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Abstract
Background: Pathogenic variants in the GNAO1 gene have been previously linked to severe epileptic encephalopathy, severe progressive movement disorders, developmental delay, and intellectual disability.
Method: report of 2 cases.
Results: we present 2 unrelated girls, an 18-year-old, and a 4.5-year-old, with mild phenotypes. While each was noted early on to have hypotonia, failure to thrive, and developmental delay, they both have made significant progress with various therapeutic interventions. Neither have had any developmental regression, seizures or choreoathetosis.
Conclusion: these 2 cases further expand the phenotype spectrum of GNAO1 mutations, which is important for counseling and to help guide management plans.
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References
- Nakamura K, Kodera H, Akita T, et al. De novo mutations in GNAO1, encoding a galphao subunit of heterotrimeric G proteins, cause epileptic encephalopathy. Am J Hum Genet. 2013;93(3):496-505. doi: 10.1016/j.ajhg.2013.07.014 [doi].
- 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(1):129-134. doi: 10.1038/ejhg.2015.92 [doi].
- Feng H, Sjogren B, Karaj B, Shaw V, Gezer A, Neubig RR. Movement disorder in GNAO1 encephalopathy associated with gain-of-function mutations. Neurology. 2017;89(8):762-770. doi: 10.1212/WNL.0000000000004262 [doi].
- Pearson TS, Helbig I. Epileptic encephalopathy, movement disorder, and the yin and yang of GNAO1 function. Neurology. 2017;89(8):754-755. doi: 10.1212/WNL.0000000000004277 [doi].
- Kulkarni N, Tang S, Bhardwaj R, Bernes S, Grebe TA. Progressive movement disorder in brothers carrying a GNAO1 mutation responsive to deep brain stimulation. J Child Neurol. 2016;31(2):211-214. doi: 10.1177/0883073815587945 [doi].
- Sakamoto S, Monden Y, Fukai R, et al. A case of severe movement disorder with GNAO1 mutation responsive to topiramate. Brain Dev. 2017;39(5):439-443. doi: S0387-7604(16)30194-2 [pii].
- Dhamija R, Mink JW, Shah BB, Goodkin HP. GNAO1-Associated Movement Disorder. Mov Disord Clin Pract. 2016;3(6):615–617. Published 2016 Mar 11. doi:10.1002/mdc3.12344
- Koy A, Cirak S, Gonzalez V, et al. Deep brain stimulation is effective in pediatric patients with GNAO1 associated severe hyperkinesia. J Neurol Sci. 2018;391:31-39. doi: S0022-510X(18)30242-9 [pii].
- Schorling DC, Dietel T, Evers C, et al. Expanding phenotype of de novo mutations in GNAO1: Four new cases and review of literature. Neuropediatrics. 2017;48(5):371-377. doi: 10.1055/s-0037-1603977 [doi].
- Danti FR, Galosi S, Romani M, et al. GNAO1 encephalopathy: Broadening the phenotype and evaluating treatment and outcome. Neurol Genet. 2017;3(2):e143. doi: 10.1212/NXG.0000000000000143 [doi].
- Retterer, K., Juusola, J., Cho, M. et al. Clinical application of whole-exome sequencing across clinical indications. Genet Med 18, 696–704 (2016). https://doi.org/10.1038/gim.2015.148
- Lek, M., Karczewski, K., Minikel, E. et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature 536, 285–291 (2016). https://doi.org/10.1038/nature19057
References
Nakamura K, Kodera H, Akita T, et al. De novo mutations in GNAO1, encoding a galphao subunit of heterotrimeric G proteins, cause epileptic encephalopathy. Am J Hum Genet. 2013;93(3):496-505. doi: 10.1016/j.ajhg.2013.07.014 [doi].
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(1):129-134. doi: 10.1038/ejhg.2015.92 [doi].
Feng H, Sjogren B, Karaj B, Shaw V, Gezer A, Neubig RR. Movement disorder in GNAO1 encephalopathy associated with gain-of-function mutations. Neurology. 2017;89(8):762-770. doi: 10.1212/WNL.0000000000004262 [doi].
Pearson TS, Helbig I. Epileptic encephalopathy, movement disorder, and the yin and yang of GNAO1 function. Neurology. 2017;89(8):754-755. doi: 10.1212/WNL.0000000000004277 [doi].
Kulkarni N, Tang S, Bhardwaj R, Bernes S, Grebe TA. Progressive movement disorder in brothers carrying a GNAO1 mutation responsive to deep brain stimulation. J Child Neurol. 2016;31(2):211-214. doi: 10.1177/0883073815587945 [doi].
Sakamoto S, Monden Y, Fukai R, et al. A case of severe movement disorder with GNAO1 mutation responsive to topiramate. Brain Dev. 2017;39(5):439-443. doi: S0387-7604(16)30194-2 [pii].
Dhamija R, Mink JW, Shah BB, Goodkin HP. GNAO1-Associated Movement Disorder. Mov Disord Clin Pract. 2016;3(6):615–617. Published 2016 Mar 11. doi:10.1002/mdc3.12344
Koy A, Cirak S, Gonzalez V, et al. Deep brain stimulation is effective in pediatric patients with GNAO1 associated severe hyperkinesia. J Neurol Sci. 2018;391:31-39. doi: S0022-510X(18)30242-9 [pii].
Schorling DC, Dietel T, Evers C, et al. Expanding phenotype of de novo mutations in GNAO1: Four new cases and review of literature. Neuropediatrics. 2017;48(5):371-377. doi: 10.1055/s-0037-1603977 [doi].
Danti FR, Galosi S, Romani M, et al. GNAO1 encephalopathy: Broadening the phenotype and evaluating treatment and outcome. Neurol Genet. 2017;3(2):e143. doi: 10.1212/NXG.0000000000000143 [doi].
Retterer, K., Juusola, J., Cho, M. et al. Clinical application of whole-exome sequencing across clinical indications. Genet Med 18, 696–704 (2016). https://doi.org/10.1038/gim.2015.148
Lek, M., Karczewski, K., Minikel, E. et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature 536, 285–291 (2016). https://doi.org/10.1038/nature19057