Cytogenetic location: 2q14.3-q21.3 Genomic coordinates (GRCh38): 2:121,600,000-136,100,000Dystonia-21 (DYT21) is an autosomal dominant form of pure torsion d...
Cytogenetic location: 2q14.3-q21.3 Genomic coordinates (GRCh38): 2:121,600,000-136,100,000
Dystonia-21 (DYT21) is an autosomal dominant form of pure torsion dystonia, a movement disorder characterized by sustained muscle contractions causing twisting and repetitive movements and abnormal postures (summary by Norgren et al., 2011).
▼ Clinical Features
Forsgren et al. (1988) reported a large Swedish kindred with autosomal dominant inheritance of dystonia. Blepharospasm and torticollis were prevalent in affected persons. The mean age of onset of the disease was 31 years, and the disease progressed from focal manifestations to generalized symptoms within 8 years.
Norgren et al. (2011) provided follow-up of the Swedish family reported by Forsgren et al. (1988), which now had 16 individuals diagnosed with torsion dystonia. The age at onset ranged between 13 and 50 years, but most had onset around age 25 years. The dystonia was mixed and included 6 patients with generalized dystonia, 7 with multifocal dystonia, 2 with segmental dystonia, and 1 with focal dystonia. All patients presented with upper body involvement of the head (mainly blepharospasm), neck, and upper limbs (hands). Two patients presented with spasmodic dysphonia. Deep brain stimulation of the pallidus was effective treatment in 4 individuals.
The transmission pattern of dystonia in the Swedish family reported by Forsgren et al. (1988) and Norgren et al. (2011) was consistent with autosomal dominant inheritance with incomplete, but high, penetrance.
By linkage analysis of a Swedish family with autosomal dominant pure dystonia, Norgren et al. (2011) identified a locus on chromosome 2q14.3-q21.3 (maximum lod score of 5.59 for marker D2S1260). The candidate region was 3.6 to 8.9 Mb long, depending on the disease status of 1 individual carrying a centromeric recombination. Mutation analysis was performed on 22 genes in the candidate region, but no pathogenic mutations were identified.