The frequency of symptomatic dystonia in relatives of patients with idiopathic focal dystonia (IFD) is higher than expected from epidemiologic studies implying that genetic factors may be involved. Perception of the vibration-induced illusion of movement (VIIM) is subnormal in patients with IFD compared with healthy volunteers and the abnormality corrects with volitional fatigue of the vibrated arm. The aim of the study was to establish the heritability of the abnormality of VIIM. The perception of illusion of movement elicited by vibration of the biceps brachii tendon before and after fatigue of the muscles was investigated in 30 patients with torticollis, 57 of their first degree relatives, and 19 healthy volunteers. VIIM did not change after fatigue in healthy controls. Before fatiguing the muscles, patients' perception of VIIM was less than healthy controls, (P < 0.01, unpaired t-test). After fatigue, the illusion of movement perceived by patients increased, so that it did not differ any more from that of the healthy control subjects (P < 0.05, repeated measures ANOVA). First degree relatives' response to vibration varied; 45% of parents, 60.7% of siblings, and 63.6% of children had an "abnormal" response to vibration compared with 21% of healthy volunteers. In contrast to patients' response, the "abnormality" did not correct after volitional fatigue of the vibrated arm. The results suggest that abnormal VIIM may represent an endophenotypic marker for IFD, which interacts with other factors including central motor learning and compensation mechanisms in the expression of the dystonic phenotype.

Background: Perception of vibration induced illusionary movement (VIIM) is subnormal in dystonic patients, suggesting abnormal sensory-motor processing in patients with idiopathic focal dystonia. Objective: To examine the effects of fatigue on VIIM in patients with idiopathic torticollis. Methods: An illusionary sensation of arm extension was evoked by an 80 Hz transcutaneous vibratory stimulus applied to the biceps brachii tendon while the arm was restrained. Blindfolded patients attempted to copy the perceived movement of the vibrated arm with the opposite (tracking) arm and the change in elbow angle of the tracking arm was quantified over 45 seconds. The tasks were repeated following volitional fatigue of the vibrated arm. Results: The subnormal perception of VIIM perceived by patients with torticollis, occurring bilaterally and remote from the location of dystonic symptoms, was corrected by fatigue of the vibrated arm compared with prefatigue values (mean (SEM): 19.04°(1.76)°v 24.25°(2.41°); p = 0.01, paired t test). Conclusions: While a combination of central or peripheral factors may be involved in the correction of abnormal perception of the vibration induced illusion of movement in dystonia, subnormal elasticity of muscle spindles could be implicated in the impaired perception of vibration induced illusionary movement and may predispose an individual towards developing idiopathic focal dystonia.

Dystonia represents a genetically and clinically heterogeneous disorder, characterized by abnormal and sustained muscle contractions and rigid postures. At least 15 different loci (DYT1-DYT15) have been identified in dystonia. Adult-onset idiopathic focal dystonia affecting specific parts of the body, such as the eye (blepharospasm), neck (cervical dystonia), and hand (writer's cramp), is mostly associated with the DYT7 locus, which was originally mapped to chromosome 18p by genomewide linkage analysis in a large family showing autosomal dominant inheritance. We have identified a family in which the mother is affected with dystonia and the son shows signs of dystonia. Using fluorescent BAC probes spanning 18p, we were able to identify a deletion in these two individuals, spanning the entire short arm of 18p. This deletion is accompanied by a centric fusion involving chromosome 14. The 18p deleted region spans 15 megabases of DNA, with a number of interesting DYT7 candidate genes, including genes involved in G-protein-coupled signaling (GNAL), cell death (CIDEA), muscle development (MYOM1 and MRLM), mitochondrial activity (NDUFV2), and neuronal function (ADYCAP1, TGIF, DAP-1, and AFG3L2).