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

Glucose transporter 1 deficiency syndrome (GLUT1-DS) is due to heterozygous mutation of the glucose transporter type 1 gene (GLUT1/SLC2A1). GLUT1-DS is characterized by movement disorders, including paroxysmal exercise-induced dystonia (PED), as well as seizures, mental retardation and hypoglycorrhachia. Tremor was recently shown to be part of the phenotype, but its clinical and electrophysiological features have not yet been described in detail, and GLUT1 tremor reports are rare. We describe two patients, a young woman and her mother, who were referred to us for tremor. We also systematically review published cases of GLUT1-DS with tremor (14 cases, including ours), focusing on clinical features. In most cases (10/14), the tremor, which involved the limbs and voice, fulfilled clinical criteria for dystonic tremor (DT), occurring in body areas affected by dystonia. Tremor was the only permanent symptom in 2 cases. Recordings, reported here for the first time, showed an irregular 6- to 8.5-Hz tremor compatible with DT in our two patients. These findings show that tremor, and particularly DT, may be a presenting symptom of GLUT1-DS. Patients who present with dystonic tremor, with or without mental retardation, seizures, movement disorders and/or a family history, should therefore be screened for GLUT1-DS.
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PMID:Dystonic tremor caused by mutation of the glucose transporter gene GLUT1. 2122 16

Primary monogenic forms of dystonia manifest solely or mainly with dystonia; they have been linked to a number of genes and loci and assigned "DYT" numbers. The pure dystonia syndrome early-onset primary dystonia (DYT1) manifests with dominantly-inherited generalized dystonia, often with focal onset in a limb. DYT1 is caused by a GAG deletion in the TOR1A gene. Mutations in the THAP1 gene cause DYT6, a form of pure dystonia that primarily involves cranio-cervical and upper limb muscles. Patients with the dystonia plus syndrome DYT5 display levodopa-responsive dystonia sometimes associated with tremor or parkinsonism (DYT5a, mutations in GCH1); a more severe phenotype with psychomotor involvement can be seen in recessive forms (DYT5b with TH mutations, SPR-deficiency syndrome). Other forms of dystonia plus syndromes include myoclonic dystonia (DYT11) and rapid-onset dystonia-parkinsonism (DYT12). Finally, paroxysmal exertion-induced dystonia (DYT18, GLUT1 deficiency) is caused by mutations in the SLC2A1 gene (DYT9 and DYT18). It is part of the paroxysmal dystonia group and manifests with paroxystic movements sometimes associated with seizures and psychomotor developmental delay.
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PMID:Overview of primary monogenic dystonia. 2216 20

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