PMID 25521004


ADCY5-related dyskinesia is characterized by infantile- to late-adolescent onset of paroxysmal choreiform, myoclonic, and/or dystonic movements that involve the limbs, neck, and/or face. Dyskinesias are often exacerbated by anxiety (although not by startle, caffeine, or alcohol). Facial ‘twitches” (previously thought to be myokymia) involving the periorbital and/or perioral muscles may also be present. Hypotonia and delayed motor milestones may be present in more severely affected infants. The movement disorder can be static or slowly progressive, with a tendency to stabilize in early middle age. Intellect and life span are normal. The diagnosis is established in a proband with a hyperkinetic movement disorder in the absence of structural brain abnormalities and confirmed by the detection of a pathogenic variant in ADCY5. Treatment of manifestations: Anecdotally, medications have had variable effect in suppressing debilitating symptoms. Treatment trials should be determined by the individual’s physician, taking into account potential risk/benefit, other medical conditions, allergies, and potential drug-drug interactions. Response to medication is difficult to evaluate because some patients have long periods (weeks) of remission of the dyskinesia. Prevention of secondary complications: Physical and occupational therapy may help maintain mobility and function. Surveillance: Most affected individuals are reevaluated annually (or more frequently if medication trials are undertaken) to document disease progression and determine if other interventions are necessary. Agents/circumstances to avoid: Known triggers (anxiety and stress) and possible triggers (intercurrent illness, prolonged inactivity, fatigue, and excitement). Pregnancy management: Potential teratogenic effects of medications given for treatment of dyskinesias should be discussed with affected women of childbearing age, ideally prior to conception. ADCY5-related dyskinesia is inherited in an autosomal dominant manner. De novo mutation has been reported. Each child of an affected individual has a 50% chance of inheriting the ADCY5 pathogenic variant. Prenatal testing for pregnancies at increased risk is possible if the ADCY5 pathogenic variant has been identified in an affected family member.