Treatment of ADCY5-Associated Dystonia, Chorea, and Hyperkinetic Disorders With Deep Brain Stimulation: A Multicenter Case Series

Marisela E Dy; Florence C F Chang; Sol De Jesus; Irina Anselm; Neil Mahant; Pamela Zeilman; Lance H Rodan; Kelly D Foote; Wen-Hann Tan; Emad Eskandar; Nutan Sharma; Michael S Okun; Victor S C Fung; Jeff L Waugh

doi:10.1177/0883073816635749

Treatment of ADCY5-Associated Dystonia, Chorea, and Hyperkinetic Disorders With Deep Brain Stimulation: A Multicenter Case Series

J Child Neurol. 2016 Jul;31(8):1027-35. doi: 10.1177/0883073816635749. Epub 2016 Apr 6.

Authors

Affiliations

¹ Department of Neurology, Boston Children's Hospital, Boston, MA, USA Department of Neurology, Massachusetts General Hospital, Boston, MA, USA Harvard Medical School, Boston, MA, USA marisela.dy@childrens.harvard.edu.
² Movement Disorders Unit, Department of Neurology, Westmead Hospital, Westmead, Australia Sydney Medical School, University of Sydney, Sydney, Australia.
³ Department of Neurology, University of Florida Center for Movement Disorders and Neurorestoration, Gainesville, FL, USA.
⁴ Department of Neurology, Boston Children's Hospital, Boston, MA, USA Harvard Medical School, Boston, MA, USA.
⁵ Harvard Medical School, Boston, MA, USA Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
⁶ Department of Neurosurgery, University of Florida Center for Movement Disorders and Neurorestoration, Gainesville, FL, USA.
⁷ Harvard Medical School, Boston, MA, USA Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA.
⁸ Department of Neurology, Boston Children's Hospital, Boston, MA, USA Department of Neurology, Massachusetts General Hospital, Boston, MA, USA Harvard Medical School, Boston, MA, USA.
⁹ Department of Neurology, University of Florida Center for Movement Disorders and Neurorestoration, Gainesville, FL, USA Department of Neurosurgery, University of Florida Center for Movement Disorders and Neurorestoration, Gainesville, FL, USA.

PMID: 27052971
DOI: 10.1177/0883073816635749

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: ADCY5; chorea; deep brain stimulation; hyperkinetic movements; whole-exome sequencing.

Publication types

Case Reports
Multicenter Study

MeSH terms

Adenylyl Cyclases / genetics*
Adult
Child
Child, Preschool
Chorea / genetics
Chorea / therapy*
Deep Brain Stimulation*
Dystonic Disorders / enzymology
Dystonic Disorders / genetics
Dystonic Disorders / therapy*
Female
Humans
Hyperkinesis / enzymology
Hyperkinesis / genetics
Hyperkinesis / therapy*
Male
Mutation*
Phenotype

Substances

Adenylyl Cyclases
adenylyl cyclase type V

Grants and funding

P01 NS087997/NS/NINDS NIH HHS/United States