Recognizing Atypical Dopa-Responsive Dystonia and Its Mimics

Abstract

Purpose of ReviewDopa-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 findingsUnlike 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.SummaryGCH-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 Parkinson's disease. Clinicians should be aware of atypical DRD, DRD-plus and DRD mimics.

Approach to the Treatment of Pediatric Dystonia

“…Furthermore, depending on the genetic cause of DRD, additional treatments with monooxidase B inhibitors (e.g., selegiline), antidepressants, tryptophane, and carbidopa might be needed. This is especially the case for the autosomal recessive forms of DRD (47,48).…”

Genetic Screening of a Hungarian Cohort with Focal Dystonia Identified Several Novel Putative Pathogenic Gene Variants

“… Abbreviations: ANO3 —anoctamin 3 [ 31 ]; ATM —ataxia-telangiectasia mutated [ 32 ]; ATP7B —ATPase copper transporting beta [ 33 ]; C19orf12 —chromosome 19 open reading frame 12 [ 34 ]; CACNA1A —calcium channel, voltage-dependent, P/Q type, alpha-1A subunit [ 35 ]; CACNA1B —calcium channel, voltage-dependent, N type, alpha-1B subunit [ 36 ]; CIZ1 —CIP1-interacting zinc finger protein [ 37 ]; COL6A3 —collagen, type VI, alpha-3 [ 38 ]; CP —ceruloplasmin [ 39 ]; DRD5 —dopamine receptor D5 [ 40 ]; FTL —ferritin light chain [ 41 ]; FUS —fused in sarcoma [ 15 ]; GCH1 —GTP cyclohydrolase 1 [ 42 ]; GNAL —guanine nucleotide-binding protein alpha-activating activity polypeptide, olfactory type [ 20 ]; KMT2B —lysine-specific methyltransferase 2B [ 43 ]; LRRK2 —leucine-rich repeat kinase 2 [ 15 ]; PANK2 —pantothenate kinase 2 [ 44 ]; PRKRA —protein kinase, interferon-inducible double-stranded RNA-dependent activator [ 17 ]; RAB12 —RAS-associated protein RAB12 [ 45 ]; REEP4 —receptor expression-enhancing protein 4 [ 16 ]; SGCE —sarcoglycan, epsilon [ 46 ]; SPR —sepiapterin reductase [ 47 ]; SYNE1 —spectrin repeat-containing nuclear envelope protein 1 [ 15 ]; TH —tyrosine hydroxylase [ 48 ]; THAP1 —THAP domain-containing protein 1 [ 49 ]; TOR1A —torsin 1A [ 50 ]; TUBB4A —tubulin, beta-4A [ 51 ]; VPS16 —VPS16 core subunit of corvet and HOPS complexes [ 52 ]; VPS41 —VPS41 subunit of HOPS complex [ 21 ]; WDR45 —WD repeat-containing protein 45 [ 53 ]. …”

Dystonia Diagnosis: Clinical Neurophysiology and Genetics

“…Moreover, diurnal fluctuations of parkinsonian symptoms due to circadian variations in dopamine concentration are more pronounced in DYT/PARK-GCH1 than in DYT/PARK-TH [ 80 ]. An adjunctive feature may help in differential diagnosis among the two forms: the presence of hypotonia is suggestive of DYT/PARK-TH, while in DYT/PARK-GCH1 hyperreflexia has been described [ 81 ]. The coexistence of non-motor features orients towards the diagnosis of DYT/PARK-GCH1, while a more complex clinical picture, with autonomic disturbances, ptosis, and oculogyric crisis is suggestive of DYT/PARK-TH.…”