Table 1.

A summary of the evidence from experimental clinical and laboratory studies suggesting that an abnormal TDT is a mediational endophenotype of cervical dystonia.

Sensitivity: the TDT is abnormal in more than 80–90% of patients with various idiopathic AOIFD phenotypes, and sensitivity is 97% in cervical dystonia (7)

Specificity: the specificity of an abnormal TDT is 98–100% (5, 7)

Autosomal dominant transmission: abnormal TDTs show autosomal dominant transmission in multiplex AOIFD families (8) and in families of sporadic cervical dystonia (9). Unaffected obligate heterozygotes have abnormal TDTs (8)

Age-related and gender-related penetrance: in unaffected first-degree female relatives, an abnormal TDT is fully penetrant by 48 years of age. In male relatives, there is 40% penetrance after 25 years of age (5)

Putaminal enlargement: unaffected relatives (of patients with cervical dystonia) with abnormal TDTs have larger putaminal volumes by VBM than relatives with normal TDTs (8). Putaminal enlargement is found in patients with blepharospasm (10) and musicians with task-related dystonia (11)

Putaminal activation: unaffected first-degree relatives (of patients with cervical dystonia) with abnormal TDTs have reduced putaminal activation in a temporal discrimination test compared to relatives with normal TDTs (5). Perceptual certainty in a temporal discrimination task is associated with putaminal activation; the putamen is involved early in a temporal processing task (12)

AOIFD, adult-onset isolated focal dystonia; TDT, temporal discrimination threshold; VBM, voxel-based morphometry.