Treatment of ADCY5 -Associated Dystonia,Chorea,and Hyperkinetic Disorders With Deep Brain Stimulation

Abstract

ADCY5 mutations have been reported as a cause of early onset hyperkinetic movements associated with delayed motor milestones, hypotonia, and exacerbation during sleep. The movement disorder may be continuous or episodic, and can vary considerably in severity within families and in individuals. The authors report a case series of 3 patients with ADCY5 mutations treated with deep brain stimulation after unsuccessful medication trials. All had extensive imaging, metabolic, and genetic testing prior to confirmation of their ADCY5 mutation. Two of the patients had the c.1252C>T; p.R418W mutation, while the youngest and most severely affected had a de novo c.2080_2088del; p.K694_M696 mutation. All had variable and incomplete, but positive responses to deep brain stimulation. The authors conclude that deep brain stimulation may provide benefit in ADCY5-related movement disorders. Long-term efficacy remains to be confirmed by longitudinal observation. ADCY5 should be considered in the differential diagnosis of early onset hyperkinetic movement disorders, and may respond to deep brain stimulation.

Keywords

chorea deep brain stimulation whole-exome sequencing hyperkinetic movements

Get full access to this article

View all access options for this article.

References

Shaw

Hisama

Friedman

Bird

. ADCY5-related dyskinesia December 18, 2014. Updated December 17, 2015. In: Pagon

Adam

Ardinger

eds. GeneReviews®. Seattle: University of Washington; 1993–2015. Available at: http://www.ncbi.nlm.nih.gov/books/NBK263441/.

Wild

Tabrizi

. The differential diagnosis of chorea. Pract Neurol. 2007;7(6):360–373.

Peall

Kurian

. Benign hereditary chorea: an update. Tremor Other Hyperkinet Mov (N Y). 2015;5:314.

Carapito

Paul

Untrau

. A de novo ADCY5 mutation causes early-onset autosomal dominant chorea and dystonia. Mov Disord. 2015;30(3):423–427.

Chen

Friedman

Chen

. Gain-of-function ADCY5 mutations in familial dyskinesia with facial myokymia. Ann Neurol. 2014;75(4):542–549.

Mencacci

Erro

Wiethoff

. ADCY5 mutations are another cause of benign hereditary chorea. Neurology. 2015;85(1):80–88.

Chen

Matsushita

Robertson

. Autosomal dominant familial dyskinesia and facial myokymia: single exome sequencing identifies a mutation in adenylyl cyclase 5. Arch Neurol. 2012;69(5):630–635.

Fernandez

Raskind

Wolff

. Familial dyskinesia and facial myokymia (FDFM): a novel movement disorder. Ann Neurol. 2001;49(4):486–492.

Raskind

Matsushita

Peter

. Familial dyskinesia and facial myokymia (FDFM): Follow-up of a large family and linkage to chromosome 3p21-3q21. Am J Med Genet Part B Neuropsychiatr Genet. 2009;150(4):570–574.

10.

Matsuoka

Suzuki

Defer

. Differential expression of type I, II, and V adenylyl cyclase gene in the postnatal developing rat brain. J Neurochem. 1997;68(2):498–506.

11.

Iwamoto

Okumura

Iwatsubo

. Motor dysfunction in type 5 adenylyl cyclase-null mice. J Biol Chem. 2003;278(19):16936–16940.

12.

Park

Kang

. Inhibition of adenylyl cyclase type 5 prevents L-DOPA-induced dyskinesia in an animal model of Parkinson’s disease. J Neurosci. 2014;34(35):11744–11753.

13.

Chang

FCF

Westenberger

Dale

. Phenotypic Insights into ADCY5-Associated Disease. Movement Disorders. Forthcoming.

14.

Lumsden

Kaminska

Gimeno

. Proportion of life lived with dystonia inversely correlates with response to pallidal deep brain stimulation in both primary and secondary childhood dystonia. Dev Med Child Neurol. 2013;55(6):567–574.

15.

Brüggemann

Kühn

Schneider

. Short- and long-term outcome of chronic pallidal neurostimulation in monogenic isolated dystonia. Neurology. 2015;84(9):895–903.

16.

Udupa

Chen

. The mechanisms of action of deep brain stimulation and ideas for the future development. Prog Neurobiol. 2015;133:27–49.

17.

Inagaki

Ohye

Suzuki

. Decrease in GTP cyclohydrolase I gene expression caused by inactivation of one allele in hereditary progressive dystonia with marked diurnal fluctuation. Biochem Biophys Res Commun. 1999;260(3):747–751.

18.

Furukawa

. GTP cyclohydrolase 1-deficient dopa-responsive dystonia. February 21, 2002. March 5, 2015. In: Pagon

Adam

Ardinger

eds. GeneReviews®. Seattle: University of Washington; 1993–2015. Available at: http://www.ncbi.nlm.nih.gov/books/NBK263441/.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB