Atypical ADCY5-related movement disorders: Highlighting adolescent/adult-onset cervical dystonia

ADCY5-related movement disorders are typically paroxysmal dyskinesia (PxDs) and/or static hyperkinetic movement disorders. Nocturnal paroxysmal dyskinesia (PxD), facial or perioral dyskinesia are suggestive of this genetic diagnosis. Next generation sequencing has enabled an expansion of the ADCY5- related phenotype.

The aim of our study was to report atypical phenotypes.

We describe 13 patients from 8 different families, of which 10 had adolescent/adult-onset head and upper limb tremor followed by static cervical dystonia without PxD. We report three novel ADCY5 variants in these patients, located in the catalytic domains, close to previously reported variants. Caffeine was ineffective for the 3 patients who tried the treatment, and botulinum toxin therapy seemed to be the most effective treatment. We also describe 2 patients with spontaneous remission of pediatric-onset PxD before adulthood.

We highlight an adolescent/adult-onset phenotype with head tremor and cervical dystonia, widening the genetic spectrum of cervical dystonia. Moreover, we broaden the pediatric ADCY5-PxD phenotype, highlighting previously unreported cases of spontaneous remission.