A patient with a GNAO1 mutation with decreased spontaneous movements, hypotonia, and dystonic features

Okumura, Akihisa; Maruyama, Koichi; Shibata, Mami; Kurahashi, Hirokazu; Ishii, Atsushi; Numoto, Shingo; Hirose, Shinichi; Kawai, Tomoko; Iso, Manami; Kataoka, Shinsuke; Muramatsu, Hideki; Kojima, Seiji

doi:10.1016/j.braindev.2018.06.005

Cited by 12 publications

(9 citation statements)

References 15 publications

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“…The genotype/phenotype may not be correlated for this gene [21]. The current patient's presentation goes with the previously reported case by Okumura et al with mild phenotype and no seizures [22]. The presence of developmental delay, hypotonia, and microcephaly in patients with well-controlled epilepsy, may reflect the considerable effect of the underlying genetic mutation on the patients' phenotype.…”

Section: Genes Responsible For Signal Transductionsupporting

confidence: 76%

The landscape of early infantile epileptic encephalopathy in a consanguineous population

Nashabat

Qahtani

Almakdob

et al. 2019

Seizure

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Epileptic encephalopathies (EE), are a group of age-related disorders characterized by intractable seizures and electroencephalogram (EEG) abnormalities that may result in cognitive and motor delay. Early infantile epileptic encephalopathies (EIEE) manifest in the first year of life. EIEE are highly heterogeneous genetically but a genetic etiology is only identified in half of the cases, typically in the form of de novo dominant mutations. Method: This is a descriptive retrospective study of a consecutive series of patients diagnosed with EIEE from the participating hospitals. A chart review was performed for all patients. The diagnosis of epileptic encephalopathy was confirmed by molecular investigations in commercial labs. In silico study was done for all novel mutations. A systematic search was done for all the types of EIEE and their correlated genes in the literature using the Online Mendelian Inheritance In Man and PubMed databases. Results: In this case series, we report 72 molecularly characterized EIEE from a highly consanguineous population, and review their clinical course. We identified 50 variants, 26 of which are novel, causing 26 different types of EIEE. Unlike outbred populations, autosomal recessive EIEE accounted for half the cases. The phenotypes ranged from self-limiting and drug-responsive to severe refractory seizures or even death. Conclusions: We reported the largest EIEE case series in the region with confirmed molecular testing and detailed clinical phenotyping. The number autosomal recessive predominance could be explained by the society's high consanguinity. We reviewed all the EIEE registered causative genes in the literature and proposed a functional classification. IntroductionEpileptic encephalopathies (EE), are disorders of the developing brain characterized by intractable seizures and electroencephalogram (EEG) abnormalities, that typically result in cognitive and motor delay, regression, and sometimes death. [1,2] Forty percent of seizures in children aged three years or less can be classified as EE [3]. Early infantile epileptic encephalopathy (EIEE) have their onset during infancy and are highly variable in etiology and natural history. While seizure is the core symptom for all EIEE syndromes often accompanied by

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Section: Genes Responsible For Signal Transductionsupporting

confidence: 76%

The landscape of early infantile epileptic encephalopathy in a consanguineous population

Nashabat

Qahtani

Almakdob

et al. 2019

Seizure

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“…It was recognized in 2016 that some GNAO1 mutations result in movement disorders without epilepsy (Kulkarni et al, 2016;Saitsu et al, 2016). To date there are over 70 published cases of children with mutations in GNAO1 presenting with early infantile epileptic encephalopathy (EIEE17: OMIM 615473) and/or neurodevelopmental disorder with involuntary movements (NEDIM: OMIM 617493) (Nakamura et al, 2013;Consortium et al, 2014;Law et al, 2015;Talvik et al, 2015;Ananth et al, 2016;Consortium, 2016;Dhamija et al, 2016;Gawlinski et al, 2016;Kulkarni et al, 2016;Marcé-Grau et al, 2016;Menke et al, 2016;Saitsu et al, 2016;Sanem et al, 2016;Arya et al, 2017;Danti et al, 2017;Sakamoto et al, 2017;Schorling et al, 2017;Blumkin et al, 2018;Bruun, 2018;Gerald et al, 2018;Honey et al, 2018;Koy et al, 2018;Marecos et al, 2018;Okumura et al, 2018;Rim et al, 2018;Schirinzi et al, 2018;Takezawa et al, 2018;Waak et al, 2018;Xiong et al, 2018;Meredith et al, 2019). This article has not been copyedited and formatted.…”

Section: Introductionmentioning

confidence: 99%

Mice with GNAO1 R209H Movement Disorder Variant Display Hyperlocomotion Alleviated by Risperidone

Larrivee

Feng

Quinn

et al. 2020

J Pharmacol Exp Ther

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“…GNAO1 – Guanosine nucleotide-binding protein G (o) subunit α is a gene that is associated with neurodevelopmental problems, including early-onset epilepsy, mild-to-severe developmental delay, and various movement disorders, from hyperkinesia to lack of spontaneous movement. [ 13 , 16 ] The mutation is our patient has been reported in at least three patients[ 7 , 18 ] and its functional effect is still unknown. [ 17 ] The genotype-phenotype correlation is still unclear.…”

Section: Discussionmentioning

confidence: 99%

Deep brain stimulation in a young child with GNAO1 mutation – Feasible and helpful

Fung

et al. 2022

Surgical Neurology International

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Background: GNAO1 is an emerging disorder characterized with hypotonia, developmental delay, epilepsy, and movement disorder, which can be potentially life threatening during acute exacerbation. In the USA, deep brain stimulation (DBS) has been licensed for treating children with chronic, treatment-resistant primary dystonia, who are 7 years old or older. Case Description: A 4-year-old girl diagnosed to have GNAO1-related dyskinesia and severe global developmental delay. She had severe dyskinesia precipitated by intercurrent infection, requiring prolonged intensive care for heavy sedation and related complications. Her dyskinesia improved dramatically after DBS implantation. Technical difficulties and precautions of DBS in preschool children were discussed. Conclusion: DBS should be considered early in the treatment of drug-resistant movement disorders in young children with GNAO1, especially after dyskinetic crisis, as they tend to recur. Presurgical counseling to parents and close monitoring of complications is also important in the process.

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A patient with a GNAO1 mutation with decreased spontaneous movements, hypotonia, and dystonic features

Cited by 12 publications

References 15 publications

The landscape of early infantile epileptic encephalopathy in a consanguineous population

The landscape of early infantile epileptic encephalopathy in a consanguineous population

Mice with GNAO1 R209H Movement Disorder Variant Display Hyperlocomotion Alleviated by Risperidone

Deep brain stimulation in a young child with GNAO1 mutation – Feasible and helpful

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