Inspired by a colleague's patient
Vijiaratnam N, Bhatia KP, Lang AE, Raskind WH, Espay AJ. ADCY5-Related Dyskinesia: Improving Clinical Detection of an Evolving Disorder. Mov Disord Clin Pract. 2019;6(7):512-520. Published 2019 Aug 19. doi:10.1002/mdc3.12816
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.
de Almeida Marcelino AL, Mainka T, Krause P, Poewe W, Ganos C, Kühn AA. Deep brain stimulation reduces (nocturnal) dyskinetic exacerbations in patients with ADCY5 mutation: a case series [published online ahead of print, 2020 Jul 9]. J Neurol. 2020;10.1007/s00415-020-09871-8. doi:10.1007/s00415-020-09871-8
Mutations in the ADCY5 gene can cause a complex hyperkinetic movement disorder. Episodic exacerbations of dyskinesia are a particularly disturbing symptom as they occur predominantly during night and interrupt sleep. We present the clinical short- and long-term effects of pallidal deep brain stimulation (DBS) in three patients with a confirmed pathogenic ADCY5 mutation. Patients were implanted with bilateral pallidal DBS at the age of 34, 20 and 13 years. Medical records were reviewed for clinical history. Pre- and postoperative video files were assessed using the "Abnormal Involuntary Movement Scale" (AIMS) as well as the motor part of the "Burke Fahn Marsden Dystonia Rating Scale" (BFMDRS). All patients reported subjective general improvement ranging from 40 to 60%, especially the reduction of nocturnal episodic dyskinesias (80-90%). Objective scales revealed only a mild decrease of involuntary movements in all and reduced dystonia in one patient. DBS-induced effects were sustained up to 13 years after implantation. We demonstrate that treatment with pallidal DBS was effective in reducing nocturnal dyskinetic exacerbations in patients with ADCY5-related movement disorder, which was sustained over the long term.
Shetty K, Sarma AS, Devan M, et al. Recurrent ADCY5 Mutation in Mosaic Form with Nocturnal Paroxysmal Dyskinesias and Video Electroencephalography Documentation of Dramatic Response to Caffeine Treatment [published online ahead of print, 2020 Jul 28]. J Mov Disord. 2020;10.14802/jmd.20014. doi:10.14802/jmd.20014 (no abstract)