Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027066 (myoclonus)
 4,275 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dystonias can be classified as primary or secondary, as dystonia-plus syndromes, and as heredodegenerative dystonias. Their prevalence is difficult to determine. In our experience 80-90% of all dystonias are primary. About 20-30% of those have a genetic background; 10-20% are secondary, with tardive dystonia and dystonia in cerebral palsy being the most common forms. If dystonia in spastic conditions is accepted as secondary dystonia, this is the most common form of all dystonia. In primary dystonias, the dystonic movements are the only symptoms. In secondary dystonias, dystonic movements result from exogenous processes directly or indirectly affecting brain parenchyma. They may be caused by focal and diffuse brain damage, drugs, chemical agents, physical interactions with the central nervous system, and indirect central nervous system effects. Dystonia-plus syndromes describe brain parenchyma processes producing predominantly dystonia together with other movement disorders. They include dopa-responsive dystonia and myoclonus-dystonia. Heredodegenerative dystonias are dystonic movements occurring in the context of other heredodegenerative disorders. They may be caused by impaired energy metabolism, impaired systemic metabolism, storage of noxious substances, oligonucleotid repeats and other processes. Pseudodystonias mimic dystonia and include psychogenic dystonia and various orthopedic, ophthalmologic, vestibular, and traumatic conditions. Unusual manifestations, unusual age of onset, suspect family history, suspect medical history, and additional signs may indicate nonprimary dystonia. If they are suspected, etiological clarification becomes necessary. Unfortunately, potential etiologies are legion. Diagnostic algorithms can be helpful. Treatment of nonprimary dystonias, with few exceptions, does not differ from treatment of primary dystonias. The most effective treatment for focal and segmental dystonias is local botulinum toxin injections. Deep brain stimulation of the globus pallidus internus is effective for generalized dystonia. Antidystonic drugs, including anticholinergics, tetrabenazine, clozapine, and gamma-aminobutyric acid receptor agonists, are less effective and often produce adverse effects. Dopamine is extremely effective in dopa-responsive dystonia. The Bertrand procedure can be effective in cervical dystonia. Other peripheral surgery, including myotomy, myectomy, neurotomy, rhizotomy, ramizectomy, and accessory nerve neurolysis, has largely been abandoned. Central surgery other than deep brain stimulation is obsolete. Adjuvant therapies, including orthoses, physiotherapy, ergotherapy, behavioral therapy, social support, and support groups, may be helpful. Analgesics should also be considered where appropriate.
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PMID:Nonprimary dystonias. 2149 5

Progressive dystonias are a clinically and genetically heterogeneous group of movement disorders. In the primary forms, dystonia is the only sign of the disease, and the cause is either unknown or genetic. In the secondary forms, dystonia is usually only one of several disease manifestations and the cause may be genetic or due to other insults. Monogenic defects have been found to underlie many forms of dystonia syndromes, which are designated DYT1-20. Dystonias with known genes include DYT1 and DYT6 dystonia, presenting as isolated torsion dystonia, as well as DYT5 (dopa-responsive dystonia), DYT11 (myoclonus-dystonia), and DYT12 (rapid-onset dystonia-parkinsonism), where dystonia occurs in conjunction with other types of movement disorders. All of these conditions follow an autosomal dominant mode of inheritance, usually develop in childhood or early adolescence, and show an initially progressive course with stabilization in early adulthood. In secondary dystonias, there are often atypical features and additional neurological signs, such as prominent tongue and perioral involvement, pyramidal signs, ataxia, oculomotor abnormalities, or cognitive disturbances. Acquired brain lesions typically affect the putamen, thalamus, or globus pallidus and cause contralateral hemidystonia. Dystonia can be part of the clinical syndrome in many heredodegenerative disorders, or may be drug-induced or psychogenic.
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PMID:Progressive dystonia. 2362 12

While Hermann Oppenheim probably described the first cases of genetic (DYT1) dystonia in 1911, the 'modern history' of dystonia genetics dates back to 1994 when mutations in the GTP cyclohydrolase I gene were discovered to cause dopa-responsive dystonia. Due to the advent of next-generation sequencing, the field of dystonia genetics has been evolving very rapidly over the past two years, resulting in the reporting of 'DYT1-25' and, for the first time, in the identification of genes associated with adult-onset focal/segmental dystonia. However, three of these putative new genes still await independent confirmation (TUBB4/DYT4; CIZ1/DYT23; ANO3/DYT24) and only 11 'DYT' genes have been unequivocally demonstrated to cause different forms of dystonia. Based on a recent consensus approach, dystonias are subdivided on clinical grounds into isolated (with or without tremor) and combined (with other movement disorders) forms. Confirmed genes for isolated dystonias include TOR1A/DYT1; THAP1/DYT6; GNAL/DYT25. In the combined forms, dystonia is accompanied by parkinsonism (GCH1/DYT5a; TH/DYT5b; ATP1A3/DYT12; TAF1/DYT3) or myoclonus (SGCE/DYT11). Persistent and paroxysmal forms are distinguished according to their temporal pattern. The paroxysmal forms of dystonia/dyskinesias present with a mixed pattern of hyperkinetic movement disorders (PRRT2/DYT10; MR-1/DYT8; SLC2A1/DYT18).
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PMID:Genetics in dystonia. 2426 66

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.
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PMID:Expanding the Spectrum of Dopa-Responsive Dystonia (DRD) and Proposal for New Definition: DRD, DRD-plus, and DRD Look-alike. 2998 92


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