title: White matter microstructural abnormalities in girls with chromosome 22q11.2 deletion syndrome, Fragile X or Turner syndrome as evidenced by diffusion tensor imaging.
abstract: Children with chromosome 22q11.2 deletion syndrome (22q11.2DS), Fragile X syndrome (FXS), or Turner syndrome (TS) are considered to belong to distinct genetic groups, as each disorder is caused by separate genetic alterations. Even so, they have similar cognitive and behavioral dysfunctions, particularly in visuospatial and numerical abilities. To assess evidence for common underlying neural microstructural alterations, we set out to determine whether these groups have partially overlapping white matter abnormalities, relative to typically developing controls. We scanned 101 female children between 7 and 14years old: 25 with 22q11.2DS, 18 with FXS, 17 with TS, and 41 aged-matched controls using diffusion tensor imaging (DTI). Anisotropy and diffusivity measures were calculated and all brain scans were nonlinearly aligned to population and site-specific templates. We performed voxel-based statistical comparisons of the DTI-derived metrics between each disease group and the controls, while adjusting for age. Girls with 22q11.2DS showed lower fractional anisotropy (FA) than controls in the association fibers of the superior and inferior longitudinal fasciculi, the splenium of the corpus callosum, and the corticospinal tract. FA was abnormally lower in girls with FXS in the posterior limbs of the internal capsule, posterior thalami, and precentral gyrus. Girls with TS had lower FA in the inferior longitudinal fasciculus, right internal capsule and left cerebellar peduncle. Partially overlapping neurodevelopmental anomalies were detected in all three neurogenetic disorders. Altered white matter integrity in the superior and inferior longitudinal fasciculi and thalamic to frontal tracts may contribute to the behavioral characteristics of all of these disorders.
authors.affiliation: Imaging Genetics Center, Laboratory of Neuro Imaging, Dept. of Neurology, University of California Los Angeles, School of Medicine, Los Angeles, CA 90095, USA.
authors.forename: Julio
authors.initials: J
authors.lastname: Villalon-Reina
authors.affiliation: Imaging Genetics Center, Laboratory of Neuro Imaging, Dept. of Neurology, University of California Los Angeles, School of Medicine, Los Angeles, CA 90095, USA.
authors.forename: Neda
authors.initials: N
authors.lastname: Jahanshad
authors.affiliation: Stress, Cognition, and Affective Neuroscience Laboratory, Department of Psychology, University of New Orleans, New Orleans, LA, 70148.
authors.forename: Elliott
authors.initials: E
authors.lastname: Beaton
authors.affiliation: Laboratory of Neuro Imaging, Dept. of Neurology, University of California Los Angeles, School of Medicine, Los Angeles, CA 90095, USA.
authors.forename: Arthur W
authors.initials: AW
authors.lastname: Toga
authors.affiliation: Imaging Genetics Center, Laboratory of Neuro Imaging, Dept. of Neurology, University of California Los Angeles, School of Medicine, Los Angeles, CA 90095, USA. Electronic address: thompson@loni.ucla.edu.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Thompson
authors.affiliation: Dept. of Psychiatry and Behavioral Sciences, University of California, Davis, Sacramento, CA, 95618, USA; MIND Institute, Dept. of Psychiatry and Behavioral Sciences, University of California, Davis, Sacramento, CA, 95618, USA.
authors.forename: Tony J
authors.initials: TJ
authors.lastname: Simon
mesh_terms: D058165:22q11 Deletion Syndrome / Q000473:pathology*; D000293:Adolescent; D016880:Anisotropy; D001921:Brain / Q000473:pathology*; D002648:Child; D056324:Diffusion Tensor Imaging; D005260:Female; D005600:Fragile X Syndrome / Q000473:pathology*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D009434:Neural Pathways / Q000473:pathology; D014424:Turner Syndrome / Q000473:pathology*
keywords: Connectivity; Diffusion tensor imaging; Genetic diseases; Neurodevelopmental diseases