Abstract
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.
Original language | English |
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Pages (from-to) | 1766-1774 |
Number of pages | 9 |
Journal | Movement Disorders |
Volume | 28 |
Issue number | 13 |
DOIs | |
Publication status | Published - Nov 2013 |
Externally published | Yes |
Keywords
- Focal dystonia
- Mediational endophenotype
- Phenotype
- Putamen
- Temporal discrimination