The Evaluation Of Environmental Factors In The Disease Penetrance Of Cervical Dystonia (P2.043)

Objective To examine the contribution of environmental risk factors to disease penetrance of cervical dystonia. Background Adult onset primary torsion dystonia (AOPTD) is a poorly penetrant autosomal dominant disorder. Most (85 -90%) gene carriers for AOPTD are non-manifesting despite having reached an adequate age for penetrance. It is hypothesized that genetic, epigenetic and environmental factors may exert protective or deleterious effects on penetrance of AOPTD. By examining environmental exposure history in cervical dystonia patients and in their similarly aged unaffected siblings we may determine the role of environment in disease penetrance. Methods A case-control, multi-centre, prospective study was performed using a 124- question standardised questionnaire collecting information on demographics and on a range of environmental exposures in patients with cervical dystonia and their unaffected siblings. The control population comprised unaffected siblings who were age- matched (-5 years/ +10 years) and, where possible, also gender- matched to their proband. Results We report the results of data collected from 67 matched sibling- pairs. Univariate logistic regression analysis showed a significant association between history of all car accidents p=0.008 (car accidents without hospitalisation p=0.046, OR 2.33, 95% CI 1.01-5.36; car accidents with hospitalisation p=0.006, 0R 5.3, 95% CI 1.59- 17.62), all surgical procedures (p=0.027, OR 5.8, 95% CI 1.22- 27.60), and ever having depression (p=0.025, OR 2.77, 95% CI 1.44- 6.77) and proband status. A multivariate model was fitted which showed that car accidents that required hospitalisation remained significantly associated with case status (p=0.013, OR 6.0, 95% CI 1.45- 28.86). Conclsuion Car accidents are often associated with soft tissue trauma, particularly minor neck trauma and likely act to increase risk of development of cervical dystonia in genetically predetermined individuals. We further propose that examination of environmental differences in unaffected relatives who carry an endophenotype (an abnormal temporal discrimination threshold) for gene carriage might strengthen findings in future environmental studies in dystonia. Disclosure: Dr. Molloy has nothing to disclose. Dr. Kimmich has nothing to disclose. Dr. Williams has nothing to disclose. Dr. Molloy has nothing to disclose. Dr. Moore has nothing to disclose. Dr. Healy has nothing to disclose. Dr. Lynch has received personal compensation for activities with Abbott, Boehringer Ingelheim Pharmaceuticals Inc., Lundbeck Research USA, Inc., Orion, Bayer Schering, Biogen Idec, and Medtronic Inc. Dr. Walsh has nothing to disclose. Dr. Reilly has nothing to disclose. Dr. O9Riordan has nothing to disclose. Dr. Hutchinson has received personal compensation for activities with Biogen Idec, Novartis, Bayer Schering, AbbVie, and Merck Serono. Dr. Hutchinson has received personal compensation in an editorial capacity for the Multiple Sclerosis Journal.