Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Presently, 17 distinct monogenic primary dystonias referred to as dystonias 1- 4, 5a,b, 6-8, 10-13 and 15-18 (loci DYT 1-4, 5a,b, 6-8, 10-13, 15-18) have been recognized. Twelve forms are inherited as autosomal dominant, four as autosomal recessive and one as an X-linked recessive trait. Three additional autosomal dominant forms (DYT9, DYT19 and DYT20) might exist based on linkage mapping to regions apparently different from, yet in close proximity to or overlapping with the known loci DYT18, DYT10 and DYT8. Clinically, this group of movement disorders includes pure dystonias and dystonia plus syndromes. In addition, dyskinesias (paroxysmal dystonias), although phenotypically distinct from classical dystonias, are discussed within this group. In pure dystonias, dystonia is occasionally accompanied by tremor. In dystonia plus syndromes, dystonia as the prominent sign concurs with other movement abnormalities such as myoclonus and parkinsonism. In the dyskinesias, dystonia occurs as a paroxysmal sign in association with other movement anomalies and sometimes seizures. While gross neuropathological changes are absent in most primary dystonias, including the paroxysmal forms, striking morphological alterations are found in some, such as in the X-linked dystonia-parkinsonism syndrome (DYT3). Neuropathological findings at the microscopic level have also been reported in several cases of dystonia 1 and 5, both of which were previously thought to be morphologically normal. One locus, DYT14 had been erroneously assigned, by linkage mapping, in a family with dystonia 5. There are two forms of dystonia 5, one autosomal dominant and one autosomal recessive. These forms are designated here as dystonia 5a and dystonia 5b (DYT5a, DYT5b), respectively. The disease gene has been identified in 10 primary dystonias, seven autosomal dominant (TOR1A/DYT1, GCH1/DYT5a, THAP1/DYT6, PNKD1/MR-1/DYT8, SGCE/DYT11, ATP1A3/DYT12 and SLC2A1/DYT18), two autosomal recessive (TH/DYT5b and PRKRA/DYT16) and one X-chromosomal recessive (TAF1/DYT3). This article summarizes all known aspects on each of the monogenic primary dystonias, including phenotype, neuropathology, imaging, inheritance, mapping, molecular genetics, molecular pathology, animal models and treatment. Suggestions for the diagnostic procedure in primary dystonias are given. Although much is now known about the molecular basis of primary dystonias, treatment of patients is still mainly symptomatic. The only exceptions are dystonias 5a and 5b with their excellent long-term response to L-dopa substitution.
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PMID:The monogenic primary dystonias. 1957 24

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

Recent consensus on the definition, phenomenology and classification of dystonia centres around phenomenology and guides our diagnostic approach for the heterogeneous group of dystonias. Current terminology classifies conditions where dystonia is the sole motor feature (apart from tremor) as 'isolated dystonia', while 'combined dystonia' refers to dystonias with other accompanying movement disorders. This review highlights recent advances in the genetics of some isolated and combined dystonic syndromes. Some genes, such as ANO3, GNAL and CIZ1, have been discovered for isolated dystonia, but they are probably not a common cause of classic cervical dystonia. Conversely, the phenotype associated with TUBB4A mutations expanded from that of isolated dystonia to a syndrome of hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC syndrome). Similarly, ATP1A3 mutations cause a wide phenotypic spectrum ranging from rapid-onset dystonia-parkinsonism to alternating hemiplegia of childhood. Other entities entailing dystonia-parkinsonism include dopamine transporter deficiency syndrome (SLC63 mutations); dopa-responsive dystonias; young-onset parkinsonism (PARKIN, PINK1 and DJ-1 mutations); PRKRA mutations; and X-linked TAF1 mutations, which rarely can also manifest in women. Clinical and genetic heterogeneity also characterizes myoclonus-dystonia, which includes not only the classical phenotype associated with epsilon-sarcoglycan mutations but rarely also presentation of ANO3 gene mutations, TITF1 gene mutations typically underlying benign hereditary chorea, and some dopamine synthesis pathway conditions due to GCH1 and TH mutations. Thus, new genes are being recognized for isolated dystonia, and the phenotype of known genes is broadening and now involves different combined dystonia syndromes.
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PMID:Isolated and combined dystonia syndromes - an update on new genes and their phenotypes. 2564 88