Extragenetic factors and clinical penetrance of DYT1 dystonia: an exploratory study

Martino, D; Gajos, A; Gallo, V; Cif, L; Coubes, P; Tinazzi, M; Schneider, SA; Fiorio, M; Zorzi, G; Nardocci, N; Ben-Shlomo, Y; Edwards, MJ; Bhatia, KP; (2013) Extragenetic factors and clinical penetrance of DYT1 dystonia: an exploratory study. Journal of neurology, 260 (4). pp. 1081-1086. ISSN 0340-5354 DOI: https://doi.org/10.1007/s00415-012-6765-2

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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 a dagger 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 a dagger 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.

Item Type: Article
Faculty and Department: Faculty of Public Health and Policy > Dept of Social and Environmental Health Research
Research Centre: Centre for Global Non-Communicable Diseases (NCDs)
PubMed ID: 23212755
Web of Science ID: 317351900017
URI: http://researchonline.lshtm.ac.uk/id/eprint/989814


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