Abstract
Factors modifying the clinical penetrance of DYT1 dystonia are incompletely defined. Particularly, the contribution of extragenetic factors has been subject to only limited investigation and remains largely unexplored. A possible effect of childhood infections has been proposed, and the effect of other factors, such as perinatal adversity and trauma, has not been systematically investigated. We performed an exploratory analysis of the exposure to perinatal adversity, childhood infections, general anaesthesia and trauma comparing 39 manifesting carriers of the ∆GAG mutation, 23 non-manifesting carriers and 48 non-carriers from a multi-centre European series of 28 families with DYT1 dystonia, by means of a self-completed questionnaire and clinical interview. Detailed information on perinatal adversities (pre-term birth, complications at natural delivery, urgent caesarean section), previous childhood infections, and prior general anaesthesia or physical trauma was recorded. A positive association between a history of complications of vaginal delivery and manifestation of dystonia was detected, which was not confounded by age, gender, or education level (odds ratio 8.47, 95 % confidence interval 1.45–49.4, p = 0.02). We could not observe any significant association between presence of dystonia and the other investigated variables. Comparing non-manifesting carriers to non-carriers, the presence of the ∆GAG mutation per se was not associated with any of the environmental exposures explored. Perinatal adversities might modulate the clinical penetrance of DYT1 dystonia; their interaction with known genetic factors modifying penetrance of this condition should be investigated in new, larger collaborative studies.
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The authors do not have any conflict of interest related to the research covered in the article.
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We state that the present study has been approved by the local ethics committee and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. As stated also in the Subjects and Methods section, all subjects gave their written informed consent prior to their inclusion in the study.
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D. Martino and A. Gajos are joint first authors.
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Martino, D., Gajos, A., Gallo, V. et al. Extragenetic factors and clinical penetrance of DYT1 dystonia: an exploratory study. J Neurol 260, 1081–1086 (2013). https://doi.org/10.1007/s00415-012-6765-2
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DOI: https://doi.org/10.1007/s00415-012-6765-2