title: Extragenetic factors and clinical penetrance of DYT1 dystonia: an exploratory study.
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.
authors.affiliation: Neuroscience and Trauma Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: D
authors.initials: D
authors.lastname: Martino
authors.forename: A
authors.initials: A
authors.lastname: Gajos
authors.forename: V
authors.initials: V
authors.lastname: Gallo
authors.forename: L
authors.initials: L
authors.lastname: Cif
authors.forename: P
authors.initials: P
authors.lastname: Coubes
authors.forename: M
authors.initials: M
authors.lastname: Tinazzi
authors.forename: S A
authors.initials: SA
authors.lastname: Schneider
authors.forename: M
authors.initials: M
authors.lastname: Fiorio
authors.forename: G
authors.initials: G
authors.lastname: Zorzi
authors.forename: N
authors.initials: N
authors.lastname: Nardocci
authors.forename: Y
authors.initials: Y
authors.lastname: Ben-Shlomo
authors.forename: M J
authors.initials: MJ
authors.lastname: Edwards
authors.forename: K P
authors.initials: KP
authors.lastname: Bhatia
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004421:Dystonia / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D004781:Environmental Exposure / Q000706:statistics & numerical data; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D007239:Infections / Q000150:complications; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D019683:Penetrance; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D018832:Molecular Chaperones; C108175:TOR1A protein, human