title: Intellectual disability and cognitive ability in Darier disease: Swedish nation-wide study.
abstract: BACKGROUND
  Darier disease is an autosomal dominant skin disorder caused by mutations in the ATP2A2 gene. Anecdotal reports suggest a relationship between Darier disease and intellectual disabilities, but these reports are based on small clinical samples and limited by absence of control populations.
  
  
  OBJECTIVE
  To examine the risk of intellectual disability and subclinical impairments in cognitive ability in Darier disease.
  
  
  METHODS
  We conducted a matched cohort study based on Swedish Population-, Patient- and Conscript Registers. The risk of being diagnosed with intellectual disability was estimated in 770 individuals with Darier disease, compared with matched comparison individuals without Darier disease. Associations were examined with risk ratios from conditional logistic regressions. In addition, we analysed test-based cognitive ability data (i.e. IQ data) from the Swedish conscript examination, for a subset of patients without diagnosed intellectual disability.
  
  
  RESULTS
  Individuals with Darier disease had a sixfold increased risk of being diagnosed with intellectual disability (risk ratio 6.2, 95% confidence interval 3.1-12.4). For conscripted individuals with Darier disease but no diagnosed intellectual disability, mean cognitive ability scores were about half a standard deviation lower than for comparison subjects.
  
  
  CONCLUSIONS
  Darier disease is associated with intellectual disability and subclinical impairments in cognitive ability. The Darier-causing mutations merit further attention in molecular genetic research on intellectual disability and cognitive ability.
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Cederlöf
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
authors.forename: R
authors.initials: R
authors.lastname: Karlsson
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Larsson
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.|Lung and Allergy Unit, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Almqvist
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
authors.forename: P K E
authors.initials: PK
authors.lastname: Magnusson
authors.affiliation: Department of Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Nordlind
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.|Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Landén
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Lichtenstein
mesh_terms: D000293:Adolescent; D003072:Cognition Disorders / Q000453:epidemiology / Q000209:etiology*; D007644:Darier Disease / Q000453:epidemiology / Q000523:psychology*; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008607:Intellectual Disability / Q000453:epidemiology / Q000209:etiology*; D008297:Male; D012307:Risk Factors; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics; D013548:Sweden / Q000453:epidemiology; D055815:Young Adult
chemical_list: D005819:Genetic Markers; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506946:ATP2A2 protein, human