Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Phenotypic insights into ADCY5-associated disease

Chang, Florence C. F., Westenberger, Ana, Dale, Russell C., Smith, Martin, Pall, Hardev S., Perez-Duenas, Belen, Grattan-Smith, Padraic, Ouvrier, Robert A., Mahant, Neil, Hanna, Bernadette C., Hunter, Matthew, Lawson, John A., Max, Christoph, Sachdev, Rani, Meyer, Esther, Crimmins, Dennis, Pryor, Donald, Morris, John G. L., Muenchau, Alex, Grozeva, Detelina ORCID: https://orcid.org/0000-0003-3239-8415, Carss, Keren J., Raymond, Lucy, Kurian, Manju A., Klein, Christine and Fung, Victor S. C. 2016. Phenotypic insights into ADCY5-associated disease. Movement Disorders 31 (7) , pp. 1033-1040. 10.1002/mds.26598

[thumbnail of Chang_et_al-2016-Movement_Disorders.pdf]
Preview
PDF - Published Version
Available under License Creative Commons Attribution.

Download (374kB) | Preview

Abstract

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. We provide detailed clinical data on 7 patients from six new kindreds with mutations in the ADCY5 gene, in order to expand and define the phenotypic spectrum of ADCY5 mutations. Methods In 5 of the 7 patients, followed over a period of 9 to 32 years, ADCY5 was sequenced by Sanger sequencing. The other 2 unrelated patients participated in studies for undiagnosed pediatric hyperkinetic movement disorders and underwent whole‐exome sequencing. Results Five patients had the previously reported p.R418W ADCY5 mutation; we also identified two novel mutations at p.R418G and p.R418Q. All patients presented with motor milestone delay, infantile‐onset action‐induced generalized choreoathetosis, dystonia, or myoclonus, with episodic exacerbations during drowsiness being a characteristic feature. Axial hypotonia, impaired upward saccades, and intellectual disability were variable features. The p.R418G and p.R418Q mutation patients had a milder phenotype. Six of seven patients had mild functional gain with clonazepam or clobazam. One patient had bilateral globus pallidal DBS at the age of 33 with marked reduction in dyskinesia, which resulted in mild functional improvement. Conclusion We further delineate the clinical features of ADCY5 gene mutations and illustrate its wide phenotypic expression. We describe mild improvement after treatment with clonazepam, clobazam, and bilateral pallidal DBS. ADCY5‐associated dyskinesia may be under‐recognized, and its diagnosis has important prognostic, genetic, and therapeutic implications.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Wiley
ISSN: 0885-3185
Date of First Compliant Deposit: 15 May 2018
Date of Acceptance: 31 January 2016
Last Modified: 23 May 2023 12:05
URI: https://orca.cardiff.ac.uk/id/eprint/110376

Citation Data

Cited 85 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics