Funding agencies: Dystonia Ireland and the Health Research Board, Ireland (CSA-2012-5).
The endophenotype and the phenotype: Temporal discrimination and adult-onset dystonia
Article first published online: 9 OCT 2013
© 2013 Movement Disorder Society
Volume 28, Issue 13, pages 1766–1774, November 2013
How to Cite
Hutchinson, M., Kimmich, O., Molloy, A., Whelan, R., Molloy, F., Lynch, T., Healy, D. G., Walsh, C., Edwards, M. J., Ozelius, L., Reilly, R. B. and O'Riordan, S. (2013), The endophenotype and the phenotype: Temporal discrimination and adult-onset dystonia. Mov. Disord., 28: 1766–1774. doi: 10.1002/mds.25676
Relevant conflicts of interest/financial disclosures: Nothing to report.
Full financial disclosures and author roles may be found in the online version of this article.
- Issue published online: 13 NOV 2013
- Article first published online: 9 OCT 2013
- Manuscript Accepted: 16 AUG 2013
- Manuscript Revised: 6 AUG 2013
- Manuscript Received: 18 NOV 2012
- focal dystonia;
- temporal discrimination;
- mediational endophenotype;
The pathogenesis and the genetic basis of adult-onset primary torsion dystonia remain poorly understood. Because of markedly reduced penetrance in this disorder, a number of endophenotypes have been proposed; many of these may be epiphenomena secondary to disease manifestation. Mediational endophenotypes represent gene expression; the study of trait (endophenotypic) rather than state (phenotypic) characteristics avoids the misattribution of secondary adaptive cerebral changes to pathogenesis. We argue that abnormal temporal discrimination is a mediational endophenotype; its use facilitates examination of the effects of age, gender, and environment on disease penetrance in adult-onset dystonia. Using abnormal temporal discrimination in unaffected first-degree relatives as a marker for gene mutation carriage may inform exome sequencing techniques in families with few affected individuals. We further hypothesize that abnormal temporal discrimination reflects dysfunction in an evolutionarily conserved subcortical-basal ganglia circuit for the detection of salient novel environmental change. The mechanisms of dysfunction in this pathway should be a focus for future research in the pathogenesis of adult-onset primary torsion dystonia. © 2013 International Parkinson and Movement Disorder Society