title: Treatment of ADCY5-Associated Dystonia, Chorea, and Hyperkinetic Disorders With Deep Brain Stimulation: A Multicenter Case Series.
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.
authors.affiliation: 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.
authors.forename: Marisela E
authors.initials: ME
authors.lastname: Dy
authors.affiliation: Movement Disorders Unit, Department of Neurology, Westmead Hospital, Westmead, Australia Sydney Medical School, University of Sydney, Sydney, Australia.
authors.forename: Florence C F
authors.initials: FC
authors.lastname: Chang
authors.affiliation: Department of Neurology, University of Florida Center for Movement Disorders and Neurorestoration, Gainesville, FL, USA.
authors.forename: Sol De
authors.initials: SD
authors.lastname: Jesus
authors.affiliation: Department of Neurology, Boston Children's Hospital, Boston, MA, USA Harvard Medical School, Boston, MA, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Anselm
authors.affiliation: Movement Disorders Unit, Department of Neurology, Westmead Hospital, Westmead, Australia Sydney Medical School, University of Sydney, Sydney, Australia.
authors.forename: Neil
authors.initials: N
authors.lastname: Mahant
authors.affiliation: Department of Neurology, University of Florida Center for Movement Disorders and Neurorestoration, Gainesville, FL, USA.
authors.forename: Pamela
authors.initials: P
authors.lastname: Zeilman
authors.affiliation: Harvard Medical School, Boston, MA, USA Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
authors.forename: Lance H
authors.initials: LH
authors.lastname: Rodan
authors.affiliation: Department of Neurosurgery, University of Florida Center for Movement Disorders and Neurorestoration, Gainesville, FL, USA.
authors.forename: Kelly D
authors.initials: KD
authors.lastname: Foote
authors.affiliation: Harvard Medical School, Boston, MA, USA Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
authors.forename: Wen-Hann
authors.initials: WH
authors.lastname: Tan
authors.affiliation: Harvard Medical School, Boston, MA, USA Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Emad
authors.initials: E
authors.lastname: Eskandar
authors.affiliation: 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.
authors.forename: Nutan
authors.initials: N
authors.lastname: Sharma
authors.affiliation: 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.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Okun
authors.affiliation: Movement Disorders Unit, Department of Neurology, Westmead Hospital, Westmead, Australia Sydney Medical School, University of Sydney, Sydney, Australia.
authors.forename: Victor S C
authors.initials: VS
authors.lastname: Fung
authors.affiliation: 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.
authors.forename: Jeff L
authors.initials: JL
authors.lastname: Waugh
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics*; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002819:Chorea / Q000235:genetics / Q000628:therapy*; D046690:Deep Brain Stimulation; D020821:Dystonic Disorders / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D005260:Female; D006801:Humans; D006948:Hyperkinesis / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D008297:Male; D009154:Mutation; D010641:Phenotype
chemical_list: D000262:Adenylyl Cyclases; C419510:adenylyl cyclase type V
keywords: ADCY5; chorea; deep brain stimulation; hyperkinetic movements; whole-exome sequencing