title: Sun exposure is an environmental factor for the development of blepharospasm.
abstract: BACKGROUND
  Adult-onset isolated focal dystonia may present with various phenotypes including blepharospasm and cervical dystonia. Although inherited in an autosomal dominant manner with a markedly reduced penetrance, environmental factors are considered important in disease penetrance and expression. We observed a marked variation by latitude in the reports of the frequency of patients with blepharospasm relative to those with cervical dystonia; we hypothesised that sun exposure is an environmental risk factor for the development of blepharospasm in genetically susceptible individuals.
  
  
  METHODS
  From published clinic cohorts and epidemiological reports, the ratio of the number of cases of blepharospasm to cervical dystonia (phenotype case ratio) at each study site was analysed with regard to latitude and measures of annual insolation. Meta-regression analyses of the phenotype case ratio to these environmental factors were performed.
  
  
  RESULTS
  The phenotype case ratio in 15 eligible study sites over 41° of latitude demonstrated a statistically significant inverse association with latitude (p=0.0004, R(2)=53.5%). There were significant positive associations between the phenotype case ratio and quarter-one (January-March) insolation (p=0.0005, R(2)=53%) and average annual insolation (p=0.003, R(2)=40%).
  
  
  CONCLUSIONS
  The increase in the blepharospasm: cervical dystonia case ratio with decreasing latitude and increasing insolation suggests that sunlight exposure is an environmental risk factor for the development of blepharospasm (rather than cervical dystonia) in individuals genetically susceptible to adult-onset dystonia.
authors.affiliation: Department of Neurology, St. Vincent's University Hospital, Dublin, Ireland School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: Anna
authors.initials: A
authors.lastname: Molloy
authors.affiliation: Department of Neurology, St. Vincent's University Hospital, Dublin, Ireland School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: Laura
authors.initials: L
authors.lastname: Williams
authors.affiliation: Department of Neurology, St. Vincent's University Hospital, Dublin, Ireland School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: Okka
authors.initials: O
authors.lastname: Kimmich
authors.affiliation: Trinity Centre for Bioengineering, Trinity College Dublin, Dublin, Ireland.
authors.forename: John S
authors.initials: JS
authors.lastname: Butler
authors.affiliation: Department of Neurology, St. Vincent's University Hospital, Dublin, Ireland School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: Ines
authors.initials: I
authors.lastname: Beiser
authors.affiliation: Department of Neurology, St. Vincent's University Hospital, Dublin, Ireland School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: Eavan
authors.initials: E
authors.lastname: McGovern
authors.affiliation: Department of Neurology, St. Vincent's University Hospital, Dublin, Ireland School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: Sean
authors.initials: S
authors.lastname: O'Riordan
authors.affiliation: Trinity Centre for Bioengineering, Trinity College Dublin, Dublin, Ireland.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Reilly
authors.affiliation: Department of Statistics, Trinity College Dublin, Dublin, Ireland Department of Mathematics and Statistics, University of Limerick, Limerick, Ireland.
authors.forename: Cathal
authors.initials: C
authors.lastname: Walsh
authors.affiliation: Department of Neurology, St. Vincent's University Hospital, Dublin, Ireland School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: Michael
authors.initials: M
authors.lastname: Hutchinson
mesh_terms: D001764:Blepharospasm / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D004777:Environment; D020022:Genetic Predisposition to Disease; D005843:Geography; D006801:Humans; D013472:Sunlight / Q000009:adverse effects*
keywords: DYSTONIA; EPIDEMIOLOGY; NEUROGENETICS