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. 2012 Aug 1:8:38.
doi: 10.1186/1744-9081-8-38.

Atlas-based white matter analysis in individuals with velo-cardio-facial syndrome (22q11.2 deletion syndrome) and unaffected siblings

Petya D Radoeva  1 , Ioana L Coman, Kevin M Antshel, Wanda Fremont, Christopher S McCarthy, Ashwini Kotkar, Dongliang Wang, Robert J Shprintzen, Wendy R Kates
Affiliations

Atlas-based white matter analysis in individuals with velo-cardio-facial syndrome (22q11.2 deletion syndrome) and unaffected siblings

Petya D Radoeva et al. Behav Brain Funct. .

Abstract

Background: Velo-cardio-facial syndrome (VCFS, MIM#192430, 22q11.2 Deletion Syndrome) is a genetic disorder caused by a deletion of about 40 genes at the q11.2 band of one copy of chromosome 22. Individuals with VCFS present with deficits in cognition and social functioning, high risk of psychiatric disorders, volumetric reductions in gray and white matter (WM) and some alterations of the WM microstructure. The goal of the current study was to characterize the WM microstructural differences in individuals with VCFS and unaffected siblings, and the correlation of WM microstructure with neuropsychological performance. We hypothesized that individuals with VCFS would have decreased indices of WM microstructure (fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD)), particularly in WM tracts to the frontal lobe, and that these measures would be correlated with cognitive functioning.

Methods: Thirty-three individuals with VCFS (21 female) and 16 unaffected siblings (8 female) participated in DTI scanning and neuropsychological testing. We performed an atlas-based analysis, extracted FA, AD, and RD measures for 54 WM tracts (27 in each hemisphere) for each participant, and used MANOVAs to compare individuals with VCFS to siblings. For WM tracts that were statistically significantly different between VCFS and siblings (pFDR <0.05), we assessed the correlations between DTI and neuropsychological measures.

Results: In VCFS individuals as compared to unaffected siblings, we found decreased FA in the uncinate fasciculus, and decreased AD in multiple WM tracts (bilateral superior and posterior corona radiata, dorsal cingulum, inferior fronto-occipital fasciculus, superior longitudinal fasciculus, superior cerebellar peduncle, posterior thalamic radiation, and left anterior corona radiata, retrolenticular part of the internal capsule, external capsule, sagittal stratum). We also found significant correlations of AD with measures of executive function, IQ, working memory, and/or social cognition.

Conclusions: Our results suggest that individuals with VCFS display abnormal WM connectivity in a widespread cerebro-anatomical network, involving tracts from/to all cerebral lobes and the cerebellum. Future studies could focus on the WM developmental trajectory in VCFS, the association of WM alterations with psychiatric disorders, and the effects of candidate 22q11.2 genes on WM anomalies.

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Figures

Figure 1
Figure 1
White matter tracts analyzed in the current report represented on the FA map of one individual with VCFS. Abbreviations: ACR: Anterior corona radiata; ALIC: Anterior limb of the internal capsule; BCC: Body of the corpus callosum; CGC: Cingulum (cingulate gyrus); CGH: Cingulum (hippocampus); EC: External capsule; Fx: Fornix (column and body of the fornix); GCC: Genu of the corpus callosum; IFO: Inferior fronto-occipital fasciculus; PLIC: Posterior limb of the internal capsule; PTR: Posterior thalamic radiation; SCR: Superior corona radiata; SS: Sagittal stratum; RLIC: Retrolenticular part of the internal capsule. For the full list of WM tracts analyzed in the current study, see the List of Abbreviations.
Figure 2
Figure 2
Significant Differences in Fractional Anisotropy ( pFDR < 0.05) in individuals with VCFS vs. siblings in the left and right uncinate fasciculi (UNC, L and UNC, R respectively). Error bars show SE.
Figure 3
Figure 3
Significant Differences in Axial Diffusivity ( pFDR < 0.05) in individuals with VCFS (black) vs. siblings (grey) in the (A) left; or (B) right sides of the brain. Error bars show SE. Abbreviations: SCP: Superior cerebellar peduncle; PTR: Posterior thalamic radiation; ACR: Anterior corona radiata; SCR: Superior corona radiata; PCR: Posterior corona radiata; CGC: Cingulum (cingulate gyrus); SLF: Superior longitudinal fasciculus; IFO: Inferior fronto-occipital fasciculus; SS: Sagittal stratum; EC: External capsule; RLIC: Retrolenticular part of the internal capsule.
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References

    1. Shprintzen RJ, Golding-Kushner KJ. Velo-Cardio-Facial Syndrome, Volume I (Genetic Syndromes and Communication Disorders) Plural Publishing Inc; 2008.
    1. Swillen A, Devriendt K, Legius E, Eyskens B, Dumoulin M, Gewillig M, Fryns JP. Intelligence and psychosocial adjustment in velocardiofacial syndrome: a study of 37 children and adolescents with VCFS. J Med Genet. 1997;34(6):453–458. doi: 10.1136/jmg.34.6.453. - DOI - PMC - PubMed
    1. Antshel KM, Fremont W, Kates WR. The neurocognitive phenotype in velo-cardio-facial syndrome: a developmental perspective. Dev Disabil Res Rev. 2008;14(1):43–51. doi: 10.1002/ddrr.7. - DOI - PubMed
    1. Kates WR, Miller AM, Abdulsabur N, Antshel KM, Conchelos J, Fremont W, Roizen N. Temporal lobe anatomy and psychiatric symptoms in velocardiofacial syndrome (22q11.2 deletion syndrome) J Am Acad Child Adolesc Psychiatr. 2006;45(5):587–595. doi: 10.1097/01.chi.0000205704.33077.4a. - DOI - PubMed
    1. Aneja A, Fremont WP, Antshel KM, Faraone SV, AbdulSabur N, Higgins AM, Shprintzen R, Kates WR. Manic symptoms and behavioral dysregulation in youth with velocardiofacial syndrome (22q11.2 deletion syndrome) J Child Adolesc Psychopharmacol. 2007;17(1):105–114. doi: 10.1089/cap.2006.0023. - DOI - PubMed

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