Bars indicate means and 95% confidence intervals. ANOVA indicates analysis of variance; HFM, healthy family member (of patients with musician’s dystonia); HM, healthy musician; MHD, musician’s hand dystonia.
Schmidt A, Jabusch H, Altenmüller E, Kasten M, Klein C. Challenges of Making Music: What Causes Musician’s Dystonia?. JAMA Neurol. 2013;70(11):1456-1459. doi:10.1001/jamaneurol.2013.3931
Musician’s dystonia, a task-specific movement disorder, affects 1% to 2% of professional musicians and is thought to be environmentally acquired, related to years of practice.1,2 Indeed, professional musicians will have spent more than 10 000 hours on the instrument by the age of 20 years.3 Recently, a clustering of different types of dystonia was reported in the families of patients with musician’s dystonia, suggesting also a genetic contribution to the disease.4 However, the underlying molecular genetic factors are currently unknown. We here investigated in a case-control design whether intensive practice or other environmental factors are associated with musician’s dystonia in combination with genetic susceptibility.
For this report, we compared 110 patients with musician’s hand dystonia with 99 healthy professional musicians (similar environment) and 61 healthy first-degree family members of the affected musicians, who, on average, share half of the genetic information with the former (similar genetic background). We studied the time spent on fine motor tasks, such as playing the instrument, writing or typing, and other potential environmental triggers,2 using structured personal interviews, neurological examination, and questionnaires.4 The study was approved by the local ethics committee and all subjects gave written informed consent. Details on the recruitment of the study sample and measurements are listed in the Table. Continuous variables were compared using analysis of variance and t tests, and categorical variables using χ2 tests supplemented with 95% confidence intervals. All tests were 2-sided, with a significance level of 0.05 and performed using IBM SPSS Statistics version 20 (SPSS Inc.
Characteristics of musicians with dystonia were consistent with earlier reports2 including predominance of males and soloists and increased frequency of positive family history compared with healthy musicians (Table). Before dystonia onset, patients had spent a mean (SD) of 26 329 (14 459) hours on their instruments and 41 834 (18 587) hours on all fine motor tasks combined with the affected hand(s). Healthy musicians had spent a nearly equal number of hours on fine motor tasks before reaching the mean age at onset of their affected counterparts. While both groups of musicians had carried out more fine motor tasks than healthy family members (mean [SD], 28 202 [16 168] hours; P < .001), patients with dystonia had started playing their instruments later (mean [SD], 10.0 [4.7] years) compared with the healthy musicians (mean [SD], 7.7 [2.2] years; P < .001; Table; Figure). The average annual practice time before the individual/mean onset of dystonia was comparable between both groups of musicians. Any potential environmental trigger within 6 months before dystonia onset was reported by 35% of the patients. Also, 79% of healthy musicians and 28% of healthy family members reported potential triggers during their lives (Table).
Our results were consistent with a complex etiologic disease model1,2 combining genetic susceptibility and environmental factors. Suggesting a genetic association, patients with dystonia had been exposed to a similar environment regarding practice time and comprised significantly more familial cases compared with the healthy musicians. In support of an environmental association, affected musicians had spent significantly more hours on all fine motor tasks than their healthy first-degree family members who shared a similar genetic background. Intriguingly, an early age at first practice was correlated with a lower risk for developing musician’s dystonia. This finding is in keeping with previous data on the use-dependent increase of related cortical brain representations in musicians, the size of which correlates with age at first practice, possibly reflecting a protective effect.5
A limitation of our study included the cross-sectional design precluding causal inferences despite biological plausibility. Furthermore, retrospective assessment of triggers may be subject to recall bias; therefore, rather than performing a direct comparison of the trigger frequencies, we documented their presence in all groups. Both limitations could be addressed by prospective study designs, a challenging but feasible task, given that there are a registered 176 200 professional musicians in the United States alone.6
Corresponding Author: Christine Klein, MD, Institute of Neurogenetics, University of Lübeck, Maria-Goeppert-Str 1, 23562 Lübeck, Germany (email@example.com).
Author Contributions: Dr Klein had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: All authors.
Acquisition of data: Schmidt, Jabusch, Altenmüller, Klein.
Analysis and interpretation of data: All authors.
Drafting of the manuscript: All authors.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Schmidt, Kasten.
Obtained funding: Schmidt, Jabusch, Altenmüller, Klein.
Study supervision: Schmidt, Jabusch, Altenmüller, Klein.
Conflict of Interest Disclosures: Dr Schmidt received research grants from the University of Lübeck for genetics research. Dr Jabusch is chairman and professor employed by the University of Music Carl Maria von Weber, Dresden, Germany. He is co-investigator of the research project Clinical and Molecular Genetics of Musician’s Dystonia partially described in this article and funded by the Dystonia Medical Research Foundation and the Bachmann-Strauss Dystonia & Parkinson's Foundation Inc. He contributed to a continuing medical education course funded by Merz Pharma GmbH, Germany. Dr Altenmüller is chairman and professor employed by the University of Music and Drama, Hanover, Germany. He serves on the editorial board of the following journals: Journal of Interdisciplinary Music Studies, Medical Problems of Performing Artists, Musicae Scientiae, and Music and Medicine. He receives research grants from the German Research Foundation (Al 269/5-3 and Al 269/7-3), the European Marie Curie Actions, the Lichtenberg Scholarship Program of Lower Saxony, and the Dystonia Medical Research Foundation. He receives royalties from the publication of the book Music, Motor Control, and the Brain, published by Oxford University Press, 2006. He received honoraria for teaching courses on the application of Botulinum-toxin A from Allergan (Botox), Ipsen Pharma (Dysport), and Desitin/Merz (Xeomin). Dr Kasten received funding from the Michael J. Fox Foundation for a 2-year postdoctoral fellowship (2004-2006), a junior research stipend for congress travel expenses (2005), a research grant from the University of Lübeck (2007), a travel grant from the Melvin Yahr Foundation (2009), and a grant from the German Research Foundation (DFG; KA3729/2-1). Dr Klein is a member of the editorial board of Neurology and has served as editor of the Continuum Issue Neurogenetics 2008 and as faculty at the Annual Meetings of the American Academy of Neurology since 2004. She received consulting fees from Boehringer Ingelheim and Centogene and honoraria for speaking from Boehringer Ingelheim and Merz Pharma. Dr Klein is the recipient of a career development award from the Hermann and Lilly Schilling Foundation. Her work is funded by the Volkswagen Foundation, the Deutsche Forschungsgemeinschaft, and the Possehl Foundation; she has received institutional support from the University of Lübeck for genetics research.
Funding/Support: This work was partially supported by the Dystonia Medical Research Foundation, the Bachmann Strauss Dystonia and Parkinson Foundation, the Dystonia Coalition, and the Deutsche Forschungsgemeinschaft.
Role of the Sponsor: The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Additional Contributions: We thank the patients and control subjects for their participation in the study.