Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied a large family with a previously undescribed, autosomal dominant dystonia-parkinsonism syndrome. We chose to call the disorder "rapid-onset dystonia-parkinsonism" (RDP) based on the unusually rapid evolution of signs and symptoms. Affected individuals developed dystonia and parkinsonism between 14 and 45 years of age. The onset was acute in six individuals with the abrupt onset of symptoms over the course of several hours, and subacute in four others who had evolution over several days or weeks. Thereafter, progression of symptoms was usually very slow. Two had intermittent focal dystonia without parkinsonism, and one obligate gene carrier was asymptomatic at 68 years. CSF levels of homovanillic acid were decreased in the two individuals tested, but dopaminergic therapy provided only slight benefit. The DYT1 gene responsible for early-onset, generalized idiopathic torsion dystonia in Jewish and some non-Jewish families has been mapped to chromosome 9q34. Linkage analysis with three markers near the DYT1 gene showed several obligate recombinations, excluding DYT1 as a candidate gene for RDP. We believe RDP is unique and should be classified separately from other forms of hereditary dystonia-parkinsonism.
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PMID:Rapid-onset dystonia-parkinsonism. 825 63

A gene (DYT1) for idiopathic torsion dystonia (ITD) was mapped to chromosome 9q34 in non-Jewish and Jewish families; the dystonia in these families usually began in childhood, with the limb muscles affected first. The role of the DYT1 gene in adult-onset and cervical- or cranial-onset ITD is unknown. We examined 53 individuals from four generations of a non-Jewish North American family with adult-onset ITD. There were seven affected family members, with a mean age at onset of 28.4 years (range, 7 to 50 years). In six of the seven, the neck was affected first. All seven developed cervical dystonia, and dysarthria or dysphonia occurred in five. Linkage data excluded the region containing the DYT1 locus, indicating that DYT1 was not responsible for ITD in this family. This study provides evidence that a gene other than DYT1 is responsible for some cases of adult cervical-onset dystonia.
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PMID:A study of idiopathic torsion dystonia in a non-Jewish family: evidence for genetic heterogeneity. 830 75

Genetic haplotypes at five marker loci that are closely linked to the DYT1 gene on chromosome 9q were determined in 10 Ashkenazi Jewish patients with focal hand dystonia (eight with musician's cramp, two with writer's cramp). The founder haplotype associated with > 90% of cases generalized dystonia in the Ashkenazi Jewish population could not be constructed from any of the twenty chromosomes. Potential haplotypes were determined, and no common haplotype was discerned in these patients. These findings argue against a role for the founder mutation in the DYT1 gene in the etiology of occupational hand dystonia in this ethnic group. Further, if the DYT1 gene is involved in these later onset dystonias, there is no evidence for a common mutation in the Ashkenazic Jewish population. It appears that excessive, repetitive use, possibly in combination with ulnar neuropathy, may serve as the inciting cause of some focal dystonias.
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PMID:Haplotype analysis at the DYT1 locus in Ashkenazi Jewish patients with occupational hand dystonia. 868 86

A large German family with "myoclonic dystonia with lightning jerks responsive to alcohol" was identified. Eleven affected pedigree members and six obligate gene carriers from five generations were identified. A description of one branch of this pedigree was published in 1964. Our examination 30 years after the initial report confirms the clinical syndrome of a nonprogressive movement disorder characterized by myoclonic jerks affecting the proximal muscles and the muscles of the trunk, accompanied by mild dystonic features in some affected family members. Segregation analysis favors autosomal dominant inheritance with high, but incomplete, penetrance in males and much lower penetrance in females. Linkage analysis was performed using simple sequence repeat polymorphisms (CA repeats) closely associated with or spanning the chromosomal regions containing 15 candidate genes: the gene for early-onset generalized torsion dystonia, DYT1 (chromosome 9q34); the genes for subunits alpha 2, beta 1, and gamma 1 (chromosome 4p12-4q13); for alpha 1, alpha 6, beta 2, and gamma 2 (chromosome 5q31.1-5q31.3); for alpha 4, alpha 5, beta 3, and gamma 3 (chromosome 15q11-15q13); for rho 1 and rho 2 (chromosome 6q14-6q21) of the gamma-aminobutyric acid A receptor; and for the alpha subunit of the glycine receptor (chromosome 5q31). By a combination of pairwise and multipoint linkage analysis, it could be excluded that any of these candidate gene-bearing chromosomal regions contain the disease gene in this family. We also excluded major portions of three chromosomal regions syntenic with mouse chromosome 3, which carries the murine beta subunit of the glycine receptor.
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PMID:Linkage studies in alcohol-responsive myoclonic dystonia. 881 14

Clinical-genetic studies of idiopathic torsion dystonia (ITD) indicate that the DYT1 gene on chromosome 9q34 is responsible for most childhood limb-onset disease. The genetic basis of adult-onset ITD is less well studied. In most multiplex adult-onset ITD families, dystonia is limited to the cervical, cranial, or brachial muscles; in a few rare families, dystonia also involves the legs and trunk. Previous linkage studies have excluded the DYT1 locus in these atypical families. We studied two large non-Jewish families with adult-onset ITD limited to the cervical and brachial muscles and excluded the DYT1-containing region. This study further restricts the role of DYT1 to childhood limb-onset ITD and suggests that other genes are responsible for focal adult-onset ITD.
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PMID:Exclusion of the DYT1 locus in familial torticollis. 887 91

A large non-Jewish Italian family affected by idiopathic torsion dystonia with autosomal dominant transmission and almost complete penetrance is reported. The prevalent phenotype was characterised by early onset with cranial-cervical involvement and progression to a segmental distribution; progression to generalisation was also found. Among 45 people examined, 14 were considered definitely or probably affected by idiopathic torsion dystonia. Eight definitely affected members had mean age (SD) at onset of 15.6 (12.5); idiopathic torsion dystonia started in the cranial-cervical region in six of them, in the upper limbs in two; in four cases dystonia progressed to other body regions, in two cases a generalisation was seen. Linkage analysis with 9q34 markers excluded the region containing the DYT1 locus in this family; linkage to the dopa-responsive dystonia markers was also excluded. A comparison of the phenotype in the present family and other non-DYT1 families shows striking overlapping features differing from those of DYT1 idiopathic torsion dystonia.
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PMID:Non-DYT1 dystonia in a large Italian family. 912 Apr 48

Early-onset (< 28 years) primary dystonia in most Ashkenazi Jews is due to a single founder mutation in the DYT1 gene on chromosome 9q34, as determined by very strong linkage disequilibrium with a haplotype of 9q34 alleles at surrounding marker loci. The role of this mutation in individuals with secondary causes for dystonia has never been tested, although environmental insults, such as neuroleptic exposure or perinatal asphyxia, are proposed to precipitate dystonia in genetically predisposed individuals. We assessed 9q34 haplotypes in 40 Ashkenazi patients with secondary dystonia; 25 had early onset of symptoms, including 15 with exposure to neuroleptic medication or perinatal asphyxia. Of the 25 patients with early onset, 9 were considered phenocopies of DYT1 having normal examinations except for dystonia, normal radiographic and other laboratory studies, and onset in a limb or the neck. Only one individual whose dystonia developed in the setting of a measles infection carried the associated haplotype. Our findings indicate that clinical diagnostic criteria that include historical information to detect tardive dystonia and perinatal asphyxia discriminate primary dystonia due to the DYT1 founder mutation. We found no evidence that the DYT1 founder mutation contributes to secondary dystonia.
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PMID:Secondary dystonia and the DYTI gene. 919 68

We report three members of a single family with an apparently autosomal dominant, nonparoxysmal, hyperkinetic movement disorder with onset in adolescence. The proband, a 56-year-old woman, manifested dystonia, tremor and myoclonus; one of her daughters exhibited myoclonus with tremor, and the other demonstrated myoclonus with chorea later accompanied by tremor and dystonia. The slowly progressive but not debilitating symptoms were restricted to the head, arms and hands and were only moderately affected by alcohol. Laboratory investigations failed to identify any abnormality, and linkage analysis excluded the region containing the DYT1 locus, indicating that the gene responsible for idiopathic torsion dystonia was not implicated in this family. While this disorder shares manifestations with myoclonic dystonia, essential myoclonus and benign chorea, the marked intrafamilial heterogeneity and the sex-limited phenotype expressed only in females of two generations appear to be unique.
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PMID:Intrafamilial heterogeneity of movement disorders: report of three cases in one family. 926 60

Early-onset torsion dystonia is a movement disorder, characterized by twisting muscle contractures, that begins in childhood. Symptoms are believed to result from altered neuronal communication in the basal ganglia. This study identifies the DYT1 gene on human chromosome 9q34 as being responsible for this dominant disease. Almost all cases of early-onset dystonia have a unique 3-bp deletion that appears to have arisen idependently in different ethnic populations. This deletion results in loss of one of a pair of glutamic-acid residues in a conserved region of a novel ATP-binding protein, termed torsinA. This protein has homologues in nematode, rat, mouse and humans, with some resemblance to the family of heat-shock proteins and Clp proteases.
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PMID:The early-onset torsion dystonia gene (DYT1) encodes an ATP-binding protein. 928 96

Idiopathic cervical dystonia (ICD) is the most common form of adult-onset focal dystonia. Previously, disagreement existed about whether ICD was a psychiatric illness, but the disorder is now viewed as a neurological illness and large clinical series have clarified the clinical features of the disease. At the time of diagnosis, extracervical dystonia is found in approximately 20% of patients, and there may be a concomitant head or hand tremor. Importantly, adult-onset ICD does not become generalized, although there may be segmental spread and pain may increase independently of the dystonia. While 10-20% of patients may experience remission, nearly all patients relapse within 5 years and are left with persistent disease. The aetiology of ICD is unknown, but there has been much progress in clarifying the genetic abnormality in families with inherited adult-onset cervical dystonia; linkage to chromosome 18p has been demonstrated in one family, and the DYT1 locus has been excluded in two other families. Painful trauma may be involved in the pathogenesis of ICD. Painful stimuli are received and processed by the basal ganglia, and the synaptic changes provoked by pain may lead to the abnormal physiology underlying dystonia. Consistent with this idea are experiments which demonstrate that altered sensory input leads to plasticity of the motor cortex, and those that explore the 'tonic vibration reflex' in patients with dystonia. Another theory suggests that a primary vestibular abnormality is responsible for ICD. Botulinum toxin is the most effective treatment for ICD. Roughly 75% of patients improve, and a response is generally seen within the first week. However, many questions remain regarding the optimal technique of administration. The development of neutralizing antibodies occurs in at least 5-10% of patients, and appears to be related both to dosage and to the interval between treatments. Side-effects are generally mild and result from the action of the toxin in the periphery. If the response to botulinum toxin is not adequate, anticholinergics, benzodiazepines, baclofen and other medications are used as adjunctive therapy. Surgical therapies are available for the treatment of ICD but are reserved for patients refractory to conservative measures.
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PMID:Current concepts on the clinical features, aetiology and management of idiopathic cervical dystonia. 957 84


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