The reference OMIM entry for this protein is 128100

Dystonia 1, torsion, autosomal dominant; dyt1
Dystonia musculorum deformans 1
Early-onset torsion dystonia; eotd

A number sign (#) is used with this entry because of evidence that torsion dystonia-1 (DYT1) is caused by heterozygous mutation in the TOR1A gene (605204), encoding the ATP-binding protein torsin-A, on chromosome 9q34.

DESCRIPTION

'Dystonia' describes a neurologic condition characterized by involuntary, sustained muscle contractions affecting one or more sites of the body; 'torsion' refers to the twisting nature of body movements observed in dystonia. Dystonia has been classified as primary (dystonia as the sole or major symptom) or secondary (a symptom of another disorder), and by age of onset, muscle groups affected, and mode of inheritance (Muller and Kupke, 1990; Nemeth, 2002).

CLINICAL FEATURES

Primary torsion dystonia (also known as 'idiopathic' torsion dystonia; ITD) usually begins in childhood or adolescence with involuntary posturing of the trunk, neck, or limbs (Marsden et al., 1976; Nemeth, 2002). Some patients have a myostatic picture, such as was described by Wechsler and Brock (1922). Johnson et al. (1962) described an extensively affected French-Canadian family. Age of onset of affected family members ranged from 6 to 42 years and severity of the disease varied considerably, with early-onset cases being severely affected. Minor manifestations interpreted as 'formes frustes' were found in some family members. In a large North American family of non-Jewish ancestry, Brin et al. (1989) found that age of onset ranged from 4 to 43 years (mean 14.4, median 10.0). Generalization occurred within a median time of 3 years and occurred earlier in cases with onset in the leg. One 6.5-year-old was unable to walk within 3 months of onset. Batshaw et al. (1985) described a patient with severe simulated torsion dystonia as the main feature of Munchausen syndrome. Bressman et al. (1994) analyzed the haplotype of 174 Ashkenazi Jewish individuals affected with torsion dystonia. In this group, there were 90 carriers of the haplotype and 70 noncarriers. The authors found very striking differences in the phenotype between carriers and noncarriers. The age of onset in carriers was 12.5 years versus 36.5 years in the noncarriers. In 94% of carriers, symptoms began in a limb but only rarely in the neck and larynx. In contrast, the neck, larynx, or other cranial muscles were the site of onset in 79% of noncarriers. Discriminant analysis of limb onset, leg involvement, and age at onset distinguished haplotype carriers from noncarriers with 90% accuracy. In 23 of the 70 noncarriers, the disease was familial and included brachial, cervical, laryngeal, and facial dystonia. Cheng et al. (1996) studied 49 probands with cervical or cranial dystonia with age of onset greater than 12 years and with a positive family history. They found that age of onset of clinical symptoms was earlier by an average of 21.25 years in the second generation than in the first, and suggested that an unstable trinucleotide repeat may be involved in adult-onset primary cranial or cervical dystonia. Grundmann et al. (2003) stated that most cases of early-onset generalized dystonia are caused by a 3-bp deletion in the DYT1 gene (delE302/303; 605204.0001). They reported 6 patients with dystonia caused by the 3-bp deletion who exhibited wide phenotypic variability: 2 had classic early-onset primary generalized dystonia, 2 had multifocal dystonia (1 with cranial and cervical muscle involvement), and 2 had only writer's cramp with mild progression. Kostic et al. ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 128100 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).