Nirosen Vijiaratnam1, Kailash P Bhatia2, Anthony E Lang3, Wendy H Raskind4, Alberto J Espay5. 1. Department of Neurology Royal Free Hospital London United Kingdom. 2. Department of Clinical and Movement Neurosciences, Queen Square Institute of Neurology University College London London United Kingdom. 3. Department of Medicine, Division of Neurology, Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital University of Toronto Toronto Ontario Canada. 4. Departments of Medicine and Psychiatry and Behavioral Sciences University of Washington Seattle Washington USA. 5. Department of Neurology (J.S.), Kingston General Hospital, Canada; Department of Neurology (D.M.-G.), Hospital Universitario Virgen del Rocío, Seville, Spain; and UC Gardner Neuroscience Institute and Gardner Family Center for Parkinson's Disease and Movement Disorders (A.Z., A.J.E.), Department of Neurology University of Cincinnati Ohio USA.
Abstract
BACKGROUND: The phenotypic spectrum of adenylyl cyclase 5 (ADCY5)-related disease has expanded considerably since the first description of the disorder in 1978 as familial essential chorea in a multiplex family. OBJECTIVE: To examine recent advances in the understanding of ADCY5-related dyskinesia and outline a diagnostic approach to enhance clinical detection. METHODS: A pragmatic review of the ADCY5 literature was undertaken to examine unique genetic and pathophysiological features as well as distinguishing clinical features. RESULTS: With over 70 cases reported to date, the phenotype is recognized to be broad, although distinctive features include prominent facial dyskinesia, motor exacerbations during drowsiness or sleep arousal, episodic painful dystonic posturing increased with stress or illness, and axial hypotonia with delayed developmental milestones. Uncommon phenotypes include childhood-onset chorea, myoclonus-dystonia, isolated nongeneralized dystonia, and alternating hemiplegia. CONCLUSION: The ongoing expansion in clinical features suggests that ADCY5 remains underdiagnosed and may account for a proportion of "idiopathic" hyperkinetic movement disorders. Enhanced understanding of its clinical features may help clinicians improve the detection of complex or uncommon cases.
BACKGROUND: The phenotypic spectrum of adenylyl cyclase 5 (ADCY5)-related disease has expanded considerably since the first description of the disorder in 1978 as familial essential chorea in a multiplex family. OBJECTIVE: To examine recent advances in the understanding of ADCY5-related dyskinesia and outline a diagnostic approach to enhance clinical detection. METHODS: A pragmatic review of the ADCY5 literature was undertaken to examine unique genetic and pathophysiological features as well as distinguishing clinical features. RESULTS: With over 70 cases reported to date, the phenotype is recognized to be broad, although distinctive features include prominent facial dyskinesia, motor exacerbations during drowsiness or sleep arousal, episodic painful dystonic posturing increased with stress or illness, and axial hypotonia with delayed developmental milestones. Uncommon phenotypes include childhood-onset chorea, myoclonus-dystonia, isolated nongeneralized dystonia, and alternating hemiplegia. CONCLUSION: The ongoing expansion in clinical features suggests that ADCY5 remains underdiagnosed and may account for a proportion of "idiopathic" hyperkinetic movement disorders. Enhanced understanding of its clinical features may help clinicians improve the detection of complex or uncommon cases.
Entities:
Keywords:
ADCY5 mutation; episodic movement disorders; phenotypic spectrum
Authors: T Onda; Y Hashimoto; M Nagai; H Kuramochi; S Saito; H Yamazaki; Y Toya; I Sakai; C J Homcy; K Nishikawa; Y Ishikawa Journal: J Biol Chem Date: 2001-10-15 Impact factor: 5.157
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