Koy, Anne, Cirak, Sebahattin, Gonzalez, Victoria, Becker, Kerstin, Roujeau, Thomas, Milesi, Christophe, Baleine, Julien, Cambonie, Gilles, Boularan, Alain, Greco, Frederic, Perrigault, Pierre-Francois, Cances, Claude, Dorison, Nathalie, Doummar, Diane, Roubertie, Agathe, Beroud, Christophe, Koerber, Friederike, Stueve, Burkhard, Waltz, Stephan, Mignot, Cyril, Nava, Caroline ORCID: 0000-0003-1272-0518, Maarouf, Mohammad, Coubes, Philippe and Cif, Laura (2018). Deep brain stimulation is effective in pediatric patients with GNAO1 associated severe hyperkinesia. J. Neurol. Sci., 391. S. 31 - 40. AMSTERDAM: ELSEVIER SCIENCE BV. ISSN 1878-5883

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Abstract

Background: Exacerbation of hyperkinesia is a life-threatening complication of dyskinetic movement disorders, which can lead to multi-organ failure and even to death. GNAO1 has been recently identified to be involved in the pathogenesis of early infantile epileptic encephalopathy and movement disorders. Patients with GNAO1 mutations can present with a severe, progressive hyperkinetic movement disorder with prolonged life-threatening exacerbations, which are refractory to most anti-dystonic medication. Objective: The objective was to investigate the evolution of symptoms and the response to deep brain stimulation of the globus pallidus internus (GPi-DBS) in patients with different GNAO1 mutations. Methods: We report six patients presenting with global motor retardation, reduced muscle tone and recurrent episodes of severe, life-threatening hyperkinesia with dystonia, choreoathetosis, and ballism since early childhood. Five of them underwent GPi-DBS. Results: The genetic workup revealed mutations in GNAO1 for all six patients. These encompass a new splice site mutation (c.723 + 1G > T) in patient 1, a new missense mutation (c.610G > C; p.Gly204Arg) in patient 2, a heterozygous mutation (c.625 > T; p.Arg209Cys) in patients 3 and 4, and a heterozygous mutation (c.709G > A; p.Glu237Lys) in patients 5 and 6. By intervention with GPi-DBS the severe paroxysmal hyperkinetic exacerbations could be stopped in five patients. One patient is still under evaluation for neuromodulation. Conclusion In complex movement disorders of unsolved etiology clinical WES can rapidly streamline pathogenic genes. We identified two novel GNAO1 mutations. GPi-DBS can be an effective and life-saving treatment option for patients with GNAO1 mutations and has to be considered early.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Koy, AnneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cirak, SebahattinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gonzalez, VictoriaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Becker, KerstinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roujeau, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Milesi, ChristopheUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baleine, JulienUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cambonie, GillesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boularan, AlainUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Greco, FredericUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Perrigault, Pierre-FrancoisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cances, ClaudeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dorison, NathalieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Doummar, DianeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roubertie, AgatheUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beroud, ChristopheUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koerber, FriederikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stueve, BurkhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Waltz, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mignot, CyrilUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nava, CarolineUNSPECIFIEDorcid.org/0000-0003-1272-0518UNSPECIFIED
Maarouf, MohammadUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Coubes, PhilippeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cif, LauraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-176455
DOI: 10.1016/j.jns.2018.05.018
Journal or Publication Title: J. Neurol. Sci.
Volume: 391
Page Range: S. 31 - 40
Date: 2018
Publisher: ELSEVIER SCIENCE BV
Place of Publication: AMSTERDAM
ISSN: 1878-5883
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
HETEROTRIMERIC G-PROTEINS; LOCAL-FIELD POTENTIALS; PARKINSONS-DISEASE; MOVEMENT-DISORDER; EPILEPTIC ENCEPHALOPATHY; GLOBUS-PALLIDUS; NOVO MUTATIONS; BASAL GANGLIA; FOLLOW-UP; DYSTONIAMultiple languages
Clinical Neurology; NeurosciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/17645

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