Session Information
Date: Wednesday, June 22, 2016
Session Title: Choreas (non-Huntington's disease)
Session Time: 12:00pm-1:30pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: We provide detailed clinical data on seven patients from six new kindreds with mutations in the ADCY5 gene, in order to expand and define the phenotypic spectrum of ADCY5 mutations.
Background: Adenylyl cyclase 5 (ADCY5) mutations is associated with heterogenous syndromes: familial dyskinesia and facial myokymia, paroxysmal chorea and dystonia, autosomal-dominant chorea and dystonia, and benign hereditary chorea.
Methods: In five of the seven patients, followed over a period of 9 to 32 years, ADCY5 gene was sequenced by Sanger sequencing. The other two unrelated patients participated in studies for undiagnosed pediatric hyperkinetic movement disorders, and underwent whole exome sequencing.
Results: Five patients, all with the p.R418W ADCY5 mutation, presented with motor milestone delay, infantile-onset action-induced generalized choreoathetosis with episodic exacerbations during drowsiness, and axial hypotonia leading to a previous diagnosis of cerebral palsy. A sixth patient with a novel p.R418G ADCY5 mutation presented with a milder phenotype of had autosomal-dominant myoclonus-dystonia. The seventh patient, carrier of a novel p.R418Q mutation, was affected by sporadic infantile-onset isolated chorea. Six out of seven patients had reduction of the episodic movement disorder with clonazepam or clobazam. All patients had infantile or childhood-onset dyskinesia that were initially episodic. In three out of seven patients, the dyskinesias became more continuous or constant with increasing age, but involuntary movements could still be absent at rest. One out of seven patients had bilateral globus pallidal deep brain stimulation at the age of 33 with marked reduction in dyskinesia which resulted in mild functional improvement.
Conclusions: We further delineate the clinical features of ADCY5 gene mutations and illustrates its wide phenotypic presentation. We describe mild improvement following treatment with clonazepam, clobazem and bilateral pallidal deep brain stimulation. ADCY5 associated dyskinesia may be under-recognized and its diagnosis has important prognostic, genetic and therapeutic implications.
To cite this abstract in AMA style:
F.C.F. Chang, A. Westenberger, R.C. Dale, M. Smith, H.S. Pall, B. Perez-Duenas, P. Grattan-Smith, R.A. Ouvrier, N. Mahant, B.C. Hanna, M. Hunter, J.A. Lawson, C. Max, R. Sachdev, E. Meyer, D. Crimmins, D. Pryor, J.G.L. Morris, A. Munchau, D. Grozeva, K.J. Carss, L. Raymond, M.A. Kurian, C. Klein, V.S.C. Fung. Phenotypic insights into ADCY5-associated disease [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/phenotypic-insights-into-adcy5-associated-disease/. Accessed May 13, 2025.« Back to 2016 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/phenotypic-insights-into-adcy5-associated-disease/