White matter microstructure in a genetically defined group at increased risk of autism symptoms, and a comparison with idiopathic autism: an exploratory study.

Marcia N Goddard,Sophie Van Rijn,Hanna Swaab,Serge A R B Rombouts

doi:10.1007/s11682-015-9496-z

Marcia N Goddard, Sophie Van Rijn + Show 2 more

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https://doi.org/10.1007/s11682-015-9496-z

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Abstract

Klinefelter syndrome (47,XXY) is associated with physical, behavioral, and cognitive consequences. Deviations in brain structure and function have been reported, but structural characteristics of white matter have barely been assessed. This exploratory diffusion tensor imaging study assessed white matter microstructure in boys with 47,XXY compared with non-clinical, male controls. Additionally, both similarities and differences between 47,XXY and autism spectrum disorders (ASD) have been reported in cognition, behavior and neural architecture. To further investigate these brain-behavior pathways, white matter microstructure in boys with 47,XXY was compared to that of boys with ASD. Fractional anisotropy (FA), radial diffusivity (Dr), axial diffusivity (Da), and mean diffusivity (MD) were assessed in 47,XXY (n = 9), ASD (n = 18), and controls (n = 14), using tract-based spatial statistics. Compared with controls, boys with 47,XXY have reduced FA, coupled with reduced Da, in the corpus callosum. Boys with 47,XXY also have reduced Dr. in the left anterior corona radiata and sagittal striatum compared with controls. Compared with boys with ASD, boys with 47,XXY show reduced Da in the right inferior fronto-occipital fasciculus. Although this study is preliminary considering the small sample size, reduced white matter integrity in the corpus callosum may be a contributing factor in the cognitive and behavioral problems associated with 47,XXY. In addition, the differences in white matter microstructure between 47,XXY and ASD may be important for our understanding of the mechanisms that are fundamental to behavioral outcome in social dysfunction, and may be targeted through intervention.

Highlights

IntroductionBoys with 47,XXY (often referred to as Klinefelter syndrome) are born with an extra X chromosome
Boys with 47,XXY are born with an extra X chromosome
To illustrate, elevated incidences of bipolar disorder, attention-deficit/ hyperactivity disorder, and autism spectrum disorders are found among individuals with 47,XXY (Bishop et al 2011; Bruining et al 2009; Cederlof et al 2014; Tartaglia et al 2010; van Rijn and Swaab 2011)

Summary

Introduction

Boys with 47,XXY (often referred to as Klinefelter syndrome) are born with an extra X chromosome. It affects approximately 1 in 650 newborns (Bojesen et al 2003) and it is not associated with marked facial or physical abnormalities, a range of physical, behavioral, and cognitive consequences may be present, to varying degrees (Giltay and Maiburg 2010; Groth et al 2013). Cognitive problems associated with 47,XXY are heterogeneous and range from subtle to quite pronounced. Intellectual functioning at the lower end of the normal range, language impairment, and executive dysfunction are among the most often reported cognitive characteristics of 47,XXY

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