Recognizing Atypical Dopa-Responsive Dystonia and Its Mimics

ABSTRACT Purpose of Review Dopa-responsive dystonia (DRD) encompasses a group of phenotypically and genetically heterogeneous neurochemical disorders. Classic GTP cyclohydrolase 1 (GCH-1)-associated DRD consists of early-onset lower limb asymetrical dystonia, with sleep benefit, diurnal variation, and excellent and sustained response to low L-dopa doses. Recent findings Unlike the classic phenotype, GCH-1-associated DRD may include features inconsistent with the original phenotype. We describe a GCH-1-associated late-onset DRD case with family history of parkinsonism and cervical dystonia whose response to levodopa was poor and complicated with dyskinesia, blepharospasm and severe non-motor symptoms. We use this case as a springboard to review the spectrum of atypical DRD, DRD-plus and DRD mimics. Summary GCH-1-related dystonia may exhibit wide intrafamilial phenotypic variability, no diurnal fluctuation, poor response to L-dopa, and such complications as dyskinesia, epilepsy, sleep disorders, autonomic dysfunction, oculogyric crisis, myoclonus, or tics. More recently, rare GCH-1 variants have been found to be associated with Parkinson9s disease. Clinicians should be aware of atypical DRD, DRD-plus and DRD mimics.