Objective To examine the age-related frequency of an abnormal temporal discrimination threshold (TDT) in unaffected first-degree relatives of patients with adult onset primary torsion dystonia (AOPTD).

Background AOPTD is an autosomal dominant condition with markedly reduced penetrance. The mean age of onset in cervical dystonia is 41 years. TDT is the shortest time interval at which two separate stimuli are detected to be asynchronous. An abnormal TDT is found in 50% of unaffected first-degree relatives of AOPTD patients and considered an endophenotype.

Methods TDTs were examined in 61 healthy control subjects and 144 unaffected first-degree relatives of AOPTD patients, using visual and tactile stimuli. Standardised Z-scores were calculated for all subjects; a Z-score greater than 2.5 was considered abnormal.

Results 65/144 (45%) of unaffected first-degree relatives had abnormal TDTs (Z-score >2.5). Abnormal TDTs were found in 19/69 (28%) of relatives 18–39 years, in 19/33 (58%) of relatives 40–49 years and in 12/20 (60%) of relatives 50–59 years of age. The frequency was significantly higher in relatives over 40 years (61%) than in those under 40 years (28%) (p=<0.0001).

Conclusion Abnormal temporal discrimination shows age-related penetrance, becoming fully penetrant after the age of 40 years. Thus a normal TDT can only be determined as not indicating non-manifesting gene carriage in relatives older than 40 years of age. The age-related penetrance of the endophenotype is similar to that of the phenotype and suggests that it is mediational in nature.