Abstract

AOPTD is autosomal dominant; the frequency of apparently sporadic cases may reflect low penetrance (12–15%). Sensory abnormalities in unaffected relatives may indicate nonmanifesting gene carriage. An ideal endophenotype in an autosomal dominant disorder should be found in all cases, 50% of first degree relatives and no controls. The TDT is the shortest time interval at which two stimuli are detected to be asynchronous. We aimed to assess the frequency of temporal discrimination threshold (TDT) abnormities in sporadic adult-onset primary torsion dystonia (AOPTD) patients and their first degree relatives. TDTs were examined in 23 sporadic Cervical Dystonia patients, 24 of their first degree relatives (10 siblings and 14 offspring) and 51 controls using visual (2 LED lights), tactile (nonpainful electrical stimulation) and mixed (1 LED, 1 electrical) stimuli. The mean TDT in controls <50 years was 24.45 ms and >50 years was 30.87 ms. The upper limit of normal was defined as control mean +2.5 SD. In the 23 cervical dystonia patients, TDT abnormalities were detected in 100% of cases. Abnormal TDTs were found in 11/24 (44%) of first degree relatives (5/10 siblings and 6/14 offspring). None of the control subjects had abnormal TDTs. The frequency of abnormalities in sporadic patients and relatives approach the ideal values for an autosomal dominant endophenotype; this supports the hypothesis that all of these cases are genetically determined with poor penetrance of the phenotype.