Pearls & Oy-sters: ADCY5-Related Dyskinesia: From a Longstanding Misdiagnosis of Drug-Resistant Epilepsy

Abstract

ADCY5-related dyskinesia (ADCY5-RD) is a hyperkinetic movement disorder of childhood onset, resulting from pathogenic variants in the ADCY5 gene. Paroxysmal worsening of the movements and movements that occur in relation to sleep and/or awakenings are hallmarks of ADCY5-RD. ADCY5-RD is therefore often misdiagnosed as sleep-related hypermotor epilepsy, sleep disorders, paroxysmal hyperkinesias, childhood onset chorea, or psychogenic events. In this case, a 59 year-old woman with a longstanding misdiagnosis of drug-resistant epilepsy was ultimately diagnosed with ADCY5-RD following video EEG. She had been followed for paroxysmal episodes of nonvoluntary movements mostly occurring during sleep since 2 years of age. She also exhibited continuous progressive dysarthria and axial hypotonia. Episodic orofacial dystonia was present as well. For 57 years, these symptoms had been treated with various combinations of antiseizure medications. However, the diagnosis was reconsidered when prolonged video-EEG monitoring recorded sleep-onset nonepileptic events, starting during N1 and N2 stages of NREM sleep. Genetic testing of ADCY5 confirmed the diagnosis. Caffeine and progressive withdrawal of antiseizure medications except clonazepam resulted in clinical improvement in paroxysms, which became less intense and less frequent. Given that ADCY5-RD was first described in 2012, there may be more adult patients misdiagnosed in childhood. Thus, we recommend considering alternative diagnosis for adult patients with paroxysmal sleep-related events to detect ADCY5-RD in adults. Although there are still no treatment guidelines for ADCY5-RD, adenosine-2A receptor antagonists have emerged as a promising therapeutic option.