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Intellectual disability and cognitive ability in Darier disease: Swedish nation-wide study

Journal article
Authors M. Cederlof
R. Karlsson
H. Larsson
C. Almqvist
P. K. E. Magnusson
K. Nordlind
Mikael Landén
P. Lichtenstein
Published in British Journal of Dermatology
Volume 173
Issue 1
Pages 155-158
ISSN 0007-0963
Publication year 2015
Published at Institute of Neuroscience and Physiology
Pages 155-158
Language en
Links dx.doi.org/10.1111/bjd.13740
Keywords MAJOR AFFECTIVE-DISORDER, ATP2A2 MUTATIONS, FAMILIAL COSEGREGATION, KERATOSIS-FOLLICULARIS, MENTAL-RETARDATION, CLINICAL-FEATURES, PHENOTYPE, ASSOCIATION, GENE, Dermatology
Subject categories Dermatology and Venereal Diseases

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. Objectives 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.

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