{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:13:19Z","timestamp":1792804399220,"version":"4.5.0"},"reference-count":46,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2016,4,8]],"date-time":"2016-04-08T00:00:00Z","timestamp":1460073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wellcome Trust","award":["WT091310"],"award-info":[{"award-number":["WT091310"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Adenylyl cyclase 5 (<jats:italic>ADCY5<\/jats:italic>) mutations is associated with heterogenous syndromes: familial dyskinesia and facial myokymia; paroxysmal chorea and dystonia; autosomal\u2010dominant chorea and dystonia; and benign hereditary chorea. We provide detailed clinical data on 7 patients from six new kindreds with mutations in the <jats:italic>ADCY5<\/jats:italic> gene, in order to expand and define the phenotypic spectrum of <jats:italic>ADCY5<\/jats:italic> mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In 5 of the 7 patients, followed over a period of 9 to 32 years, <jats:italic>ADCY5<\/jats:italic> was sequenced by Sanger sequencing. The other 2 unrelated patients participated in studies for undiagnosed pediatric hyperkinetic movement disorders and underwent whole\u2010exome sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Five patients had the previously reported p.R418W <jats:italic>ADCY5<\/jats:italic> mutation; we also identified two novel mutations at p.R418G and p.R418Q. All patients presented with motor milestone delay, infantile\u2010onset action\u2010induced 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We further delineate the clinical features of <jats:italic>ADCY5<\/jats:italic> gene mutations and illustrate its wide phenotypic expression. We describe mild improvement after treatment with clonazepam, clobazam, and bilateral pallidal DBS. <jats:italic>ADCY5<\/jats:italic>\u2010associated dyskinesia may be under\u2010recognized, and its diagnosis has important prognostic, genetic, and therapeutic implications. \u00a9 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.26598","type":"journal-article","created":{"date-parts":[[2016,4,10]],"date-time":"2016-04-10T14:15:32Z","timestamp":1460297732000},"page":"1033-1040","source":"Crossref","is-referenced-by-count":126,"title":["Phenotypic insights into <i>ADCY5<\/i>\u2010associated disease"],"prefix":"10.1002","volume":"31","author":[{"given":"Florence C.F.","family":"Chang","sequence":"first","affiliation":[{"name":"Movement Disorders Unit, Department of Neurology Westmead Hospital Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Westenberger","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell 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