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Dear Editor, Primary paroxysmal dyskinesias (PxDs) are a highly heterogeneous group of disorders with several causative genes. Mutations in one such gene, ADCY5, commonly present with dystonia, chorea, myoclonus or a combination of the above.1-3 Neurological manifestations of ADCY5 mutations include the following core clinical features: continuous dyskinesias, ballistic bouts, paroxysmal sleep-related dyskinesias and axial hypotonia. Other rare symptoms include cognitive impairment, psychiatric symptoms, etc. Rarely, nonneurological manifestations including cardiomyopathy have been reported. Various drug treatments have been attempted with only modest responses; however, a dramatic response to caffeine was recently reported.4,5 We would like to report a patient with a mosaic mutation in ADCY5 presenting with pure PxD and a dramatic response to caffeine therapy. A 32 year-old male born to nonconsanguineous parentage with no history of perinatal birth injury presented in November 2018 with paroxysmal involuntary movements during sleep from the age of 4 years. For each paroxysmal event, arousal from sleep occurred just before the motor phenomenon, as noted by onset of posterior alpha rhythm on video electroencephalography (video EEG). This was followed by involuntary movements consisting of generalized non-patterned choreiform with dystonic movements, better described as generalized dyskinesia or ‘ballistic bouts.’4 Each event lasted approximately 3 minutes with preserved awareness throughout the event confirmed by clinical assessment (Supplementary Video 1 and 2 in the online-only Data Supplement). The patient experienced similar events during daytime naps. The patient experienced approximately 20–30 events per night (cumulating to 60–90 minutes of involuntary movements per night). The events more often occurred in early morning hours and in winter. Interictal examination, MRI brain scan and basic metabolic work-up were normal. In view of a classical history of long-standing, exclusively sleep-related, brief paroxysmal dyskinesia without any movement/exercise related triggers, PxD related to a de novo ADCY5 mutation (in view of a negative family history) was clinically diagnosed over other clinical differentials. Whole exome sequencing was performed due to the genetic heterogeneity of PxD. A known pathogenic variant was identified in the ADCY5 gene (NM_183357.2:Exon 2:c.1252C > T:p.R418W). Further exome data analysis revealed that the variant was mosaic with low mutant read depth (Total depth: 85, Wildtype: 72, Mutant: 13). The effect of this variant was tested ac-

journal of movement disorders

Recurrent ADCY5 Mutation in Mosaic Form with Nocturnal Paroxysmal Dyskinesias and Video Electroencephalography Documentation of Dramatic Response to Caffeine Treatment