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. 2020 Dec 9;15(1):343.
doi: 10.1186/s13023-020-01594-3.

Spectrum of movement disorders in GNAO1 encephalopathy: in-depth phenotyping and case-by-case analysis

Soo Yeon Kim  1   2 , YoungKyu Shim  1 , Young Joon Ko  1 , Soojin Park  1   3 , Se Song Jang  1 , Byung Chan Lim  1   2   4 , Ki Joong Kim  1   4 , Jong-Hee Chae  5   6   7
Affiliations

Spectrum of movement disorders in GNAO1 encephalopathy: in-depth phenotyping and case-by-case analysis

Soo Yeon Kim et al. Orphanet J Rare Dis. .

Abstract

Background: GNAO1 encephalopathy is a rare neurodevelopmental disorder characterized by distinct movement presentations and early onset epileptic encephalopathy. Here, we report the in-depth phenotyping of genetically confirmed patients with GNAO1 encephalopathy, focusing on movement presentations.

Results: Six patients who participated in Korean Undiagnosed Disease Program were diagnosed to have pathogenic or likely pathogenic variants in GNAO1 using whole exome sequencing. All medical records and personal video clips were analyzed with a literature review. Three of the 6 patients were male. Median follow-up duration was 41 months (range 7-78 months) and age at last examination was 7.4 years (range 3.3-16.9 years). Initial complaints were hypotonia or developmental delay in 5 and right-hand clumsiness in 1 patient, which were noticed at median age of 3 months (range 0-75 months). All patients showed global developmental delay and 4 had severely retarded development. Five patients (5/6, 83.3%) had many different movement symptoms with various onset and progression. The symptoms included stereotyped hands movement, non-epileptic myoclonus, dyskinesia, dystonia and choreoathetosis. Whole exome sequencing identified 6 different variants in GNAO1. Three were novel de novo variants and atypical presentation was noted in a patient. One variant turned out to be inherited from patient's mother who had mosaic variant. Distinct and characteristics movement phenotypes in patients with variant p.Glu246Lys and p.Arg209His were elucidated by in-depth phenotyping and literature review.

Conclusions: We reported 6 patients with GNAO1 encephalopathy showing an extremely diverse clinical spectrum on video. Some characteristic movement features identified by careful inspection may also provide important diagnostic insight and practice guidelines.

Keywords: Early-onset chorea; Early-onset dystonia; GNAO1; GNAO1 encephalopathy; Movement disorder.

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Conflict of interest statement

The authors have no conflict of interest or financial relationship to disclose.

Figures

Fig. 1
Fig. 1
Pedigree and result of genetic testing of patient 5 who carried the variant p.Arg209His. Sanger sequencing analysis indicated the mother’s heterozygous peak. The result of sequential barcoded amplicon sequencing is described and the patient’s mother carried a somatic mutation
See this image and copyright information in PMC

References

    1. Nakamura K, Kodera H, Akita T, Shiina M, Kato M, Hoshino H, 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 - PMC - PubMed
    1. 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 - PubMed
    1. Gawlinski P, Posmyk R, Gambin T, Sielicka D, Chorazy M, Nowakowska B, et al. PEHO syndrome may represent phenotypic expansion at the severe end of the early-onset encephalopathies. Pediatr Neurol. 2016;60:83–87. doi: 10.1016/j.pediatrneurol.2016.03.011. - DOI - PMC - PubMed
    1. Schorling DC, Dietel T, Evers C, Hinderhofer K, Korinthenberg R, Ezzo D, 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 - PubMed
    1. 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(1):67–75. doi: 10.1684/epd.2017.0888. - DOI - PubMed

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