Scoping review on ADCY5-related movement disorders

Background Adenylyl cyclase 5 (ADCY5)-related movement disorder (ADCY5-RMD) is a rare, childhood-onset disease resulting from pathogenic variants in the ADCY5 gene. The clinical features, diagnostic options, natural history, and treatments for this disease are poorly characterized and have never been established through a structured approach. Objective This scoping review attempts to summarize all available clinical literature on ADCY5-RMD. Methods Eighty-seven articles were selected for inclusion in this scoping review. The majority of articles identified were case reports or case series. Results These articles demonstrate that patients with ADCY5-RMD suffer from permanent and/ or paroxysmal hyperkinetic movements. The paroxysmal episodes can be worsened by environmental triggers, in particular the sleep–wake transition phase in the early morning. Occurrence of nocturnal paroxysmal dyskinesias and perioral twitches are highly suggestive of the diagnosis when present. In the majority of patients intellectual capacity is preserved. ADCY5-RMD is considered a non-progressive disorder, with inter-individual variations in evolution with aging. Somatic mosaicism, mode of inheritance and the location of the mutation within the protein can influence phenotype. Conclusions The current evidence for therapeutic options for ADCY5-RMD is limited: caffeine, benzodiazepines and deep brain stimulation have been consistently reported to be useful in case reports and case series.