Expanding the Spectrum of Dopa-Responsive Dystonia (DRD) and Proposal for New Definition: DRD, DRD-plus, and DRD Look-alike

Abstract

Previously, we defined DRD as a syndrome of selective nigrostriatal dopamine deficiency caused by genetic defects in the dopamine synthetic pathway without nigral cell loss. DRD-plus also has the same etiologic background with DRD, but DRD-plus patients have more severe features that are not seen in DRD because of the severity of the genetic defect. However, there have been many reports of dystonia responsive to dopaminergic drugs that do not fit into DRD or DRD-plus (genetic defects in the dopamine synthetic pathway without nigral cell loss). We reframed the concept of DRD/DRD-plus and proposed the concept of DRD look-alike to include the additional cases described above. Examples of dystonia that is responsive to dopaminergic drugs include the following: transportopathies (dopamine transporter deficiency; vesicular monoamine transporter 2 deficiency); SOX6 mutation resulting in a developmentally decreased number of nigral cells; degenerative disorders with progressive loss of nigral cells (juvenile Parkinson's disease; pallidopyramidal syndrome; spinocerebellar ataxia type 3), and disorders that are not known to affect the nigrostriatal dopaminergic system (DYT1; GLUT1 deficiency; myoclonus-dystonia; ataxia telangiectasia). This classification will help with an etiologic diagnosis as well as planning the work up and guiding the therapy.

Dopamine receptor D2 and ankyrin repeat domain containing one in temporomandibular disorder of adolescents

“…Neurotransmitters, such as cortisol, serotonin, epinephrine, and dopamine, influence a cascade of physiological reactions in the body and emotional states . Especially in adolescence, neurotransmitters are essential to guarantee the homeostasis of a body that is undergoing a period of great physical, emotional, and behavioural changes, fundamental for the entrance of the adolescent into adult life.…”

“…Dopamine is responsible for the transduction of nerve signals, and for this, specific proteins are required . Since these proteins are encoded by the DRD2 and ANKK1 genes, both are strong candidates to be studied in situations in which stress, anxiety, and pain are present.…”

“…The DRD2 protein is encoded by Dopamine Receptor D2 ( DRD2 ) and Ankyrin Repeat Domain Containing One (ANKK1) genes that have similar pattern of association . Genetic polymorphisms in these genes have been associated with sleep disturbances, acute, chronic pain, myofascial pain, and migraine .…”

Current therapies and therapeutic decision making for childhood‐onset movement disorders

“…These neurotransmitter conditions are the reason all children with unexplained dystonia or akinesia should have a l ‐dopa trial, particularly in the context of a normal MRI and suggestive clinical features, as above. Complete dopa responsiveness is suggestive of a primary neurotransmitter condition and sometimes other monogenic disorders such as PARKIN deletions; however, varying dopamine responsiveness can be observed in some other genetic nonprogressive disorders (DNAJC12, DYT11, paroxyxmal kinesigenic and nonkinesigenic dyskinesia, and pyruvate dehydrogenase complex deficiency), genetic‐progressive disorders (ataxia telangiectasia, chorea acanthocytosis, DJ‐1, FBX07, Kufor‐Rakeb disease, nuclear inclusion body disease, PINK1, pantothenate kinase associated neurodegeneration, PLA2G6 associated neurodegeneration, pontocerebellar hypoplasia type 2, SCA2, SCA3, SOX6, SPG11, and xeroderma pigmentosum), and, to a lesser extent, in acquired disorders such as movement disorders with lupus, organophosphate poisoning, subacute sclerosing panencephalitis, postencephalitic dystonia, or extrapontine myelinolysis. The role of l ‐dopa in management of dystonic cerebral palsy (CP) is questionable and results from previous studies are contradictory …”

Diagnosing Unusual Presentations of Dopa-Responsive Conditions: Thinking on your Feet

“…1,2 To add to this repertoire, several phenotypes have been described in the literature as being "dopa-responsive" which may or may not be associated with selective nigrostriatal dopamine deficiency but respond remarkably well to dopaminergic drugs. 2 In a recent review, Lee et al have tried to segregate these disorders into DRD, DRD-plus and a third group called DRD-look-alike. 2 The DRD and DRD-plus group involve nigrostriatal dopaminergic pathways with the difference being in their clinical presentation.…”