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 14 years 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.

Complex Neurological Phenotype in Female Carriers of <b><i>NHE6</i></b> Mutations

“…Such deficits may be linked to the frontoparietal white and gray matter abnormalities [22, 25], consistent with the known localization of visuospatial and executive functions to the parietal and frontal regions, respectively. Alternatively, as the lateral and posterior cerebellar regions are involved in visuospatial and executive functions [26] and given the cerebellar atrophy observed in some CS probands [2], cerebellar involvement could be the underlying mechanism of impaired visuospatial and executive functioning in female carriers.…”

Abnormalities in brain white matter in adolescents with 22q11.2 deletion syndrome and psychotic symptoms

“…In fact, studies in school age children with 22q11DS report reduced FA and increased RD in the fornix (Deng et al 2015) and in the superior longitudinal fasciculi, the inferior longitudinal fasciculi, the splenium of the corpus callosum, and the corticospinal tract (Villalon-Reina et al 2013), which might be interpreted as abnormal myelination in 22q11DS in early childhood. In another study, where subjects of older age and a wider age range were included (10 thorough 26 years old), increased FA and reduced AD and RD were reported in several tracts in 22q11DS (Jalbrzikowski et al, 2014).…”

“…The syndrome is characterized by a copy number variation (CNV), namely a deletion of over 40 genes on one copy of chromosome 22 (Karayiorgou et al 1995; Murphy et al 1999). White matter abnormalities are present in 22q11DS and include reduced FA in interhemispheric connections, as well as across the frontal, parietal , temporal and limbic regions (Villalon-Reina et al 2013; Sundram et al 2010; Simon et al 2005; Barnea-Goraly et al 2003; Kates et al 2015; Perlstein et al 2014; Deng et al 2015; da Silva Alves et al 2011; Jalbrzikowski et al 2014; Radoeva et al 2012; Barnea-Goraly et al 2005) . Abnormalities in maturational trajectories of white matter development (based on cross-sectional data) have also been reported in children and young adults with 22q11DS (Jalbrzikowski et al 2014).…”

Brain Imaging and Neurodevelopment in HIV-uninfected Thai Children Born to HIV-infected Mothers

“…These findings add confidence that our methodologies had sufficient power to detect associations between brain measures and cognition. DTI studies of similar age groups and with similar or smaller sample sizes have successfully identified microstructural abnormalities in children with neurogenetic disorders 49 or behavior problems 50 . The differences observed in these studies highlight the power of DTI to identify neuroanatomical changes associated with childhood conditions and adds confidence that we had the power to identify differences in the current study.…”