Corpus callosum morphology and ventricular size in chromosome 22q11.2 deletion syndrome

Abstract

In this paper, novel methods were used to map the corpus callosum morphology of children with chromosome 22q11.2 deletion syndrome in order to further investigate changes to that structure and to examine their possible effects on cognitive function. The callosal profiles were extracted from the centermost MRI midsagittal slice by supervised thresholding and the structure's boundary and midline were computed automatically. Difference analysis was based on non-rigid registration, in which a template image is warped to conform to the shape of each corpus callosum in the sample. Boundaries and midlines were registered to a template and the results used to determine the average callosal shapes for children with the deletion and for controls. Point-wise registration also enabled the detailed evaluation of callosal curvature, width, area and length. Significant differences between the two groups were found in shape, size and bending angle. Results showed group differences that were concentrated in the anterior part of the structure, more specifically in the rostrum, which was larger and longer in the group with the syndrome. Correlation analyses showed that ventricular enlargement does not fully account for callosal morphology differences in children with the deletion. However, areal measurements did reveal important relationships between changes in callosal morphology and cognitive function. These novel findings reveal intricate relationships between genetic and disease-specific factors in the callosal anatomy and the potential impact of those changes on cognitive functions. KeywordsChildren; chromosome 22q11.2 deletion syndrome; cognition; corpus callosum; morphology; image registration 1) INTRODUCTIONChromosome 22q11.2 deletion syndrome (DS22q11.2) results from a 1.5 -3Mb microdeletion on the long (q) arm of chromosome 22 (Driscoll, 1992a(Driscoll, , 1992b and encompasses the phenotypes of DiGeorge (DiGeorge, 1965), Velocardiofacial (Shprintzen, 1978) and * Corresponding Author Av. Dom José Gaspar, 500, PPGEE, Belo Horizonte, MG, Brazil, 30535-610 Phone: +5531 33194305 Fax: +5531 33194225 e-mail: alexei@grasp.cis.upenn.edu Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptConotruncal Anomaly Face (Burn, 1993) syndromes, and some cases of Cayler Cardiofacial syndrome (Giannotti, 1994) and Opitz G/BBB syndrome (McDonald-McGinn, 1995). Prevalence is thought to be around 1 in 4000 to 1 in 7000 live births (Burn, 1996). Following characterization of a range of medical manifestations ...

A new account of the neurocognitive foundations of impairments in space, time, and number processing in children with chromosome 22q11.2 deletion syndrome

“…Having demonstrated (Simon et al 2005a) that children with DS22q11.2 could not perform as well as TD controls children, we used a new task requiring children to simply choose the larger of a pair of objects, either bars varying in length differences of 1 to 7cm or Arabic numbers varying in numerical differences of 1 to 7. . Our results (Simon et al 2007) show both a significant increase in response time for all distances and significantly greater response times with increasing number in the DS22q11.2 group. Slopes for distances 1−5 indicated were significantly larger for the DS22q11.2 than the TD group (p=.001); DS22q11.2 97.86ms/distance vs. TD 45.43ms/distance for blocks and 100.29ms/distance vs. 30.88ms/distance for numbers.…”

“…We recently reported (Machado et al 2007) that at least one change in the corpus callosum (its area) relates quite differently to performance on the attentionally demanding counting part of the enumeration task described earlier in children with DS22q11.2 than in TD controls. This suggests that affected children may be using a different, and atypical, cortical network to complete this task and this may partially explain their difficulties.…”

“…Campbell's (2006) study used a manual tracing technique and reported significantly larger ventricular volumes in children with the deletion than in the controls. Machado (2007) reported that the ventricles from the same children Simon's (2005c) whole brain study were segmented using a semiautomated method and, again, significantly larger volumes were found in children with the deletion.…”

Increased corpus callosum volume in children with chromosome 22q11.2 deletion syndrome is associated with neurocognitive deficits and genetic polymorphisms

“…Previous studies in children with 22q11DS had examined the area of the CC in the mid-sagittal plane, [20][21][22] but differences in fiber density within the CC can result in asymmetries that, in turn, can affect area measurements. 34 Volumetric measurements are less subject to such variances and would thus be more accurate.…”

“…19 We previously reported that the CC area was larger in children with 22q11DS, compared with typically developing children, 20 replicated by others. [21][22][23] Relatively little is known about the association between the CC size and the neurocognitive/psychiatric manifestations of 22q11DS, with one report of an association between ADHD and smaller CC area 21 and another of faster enumeration skills with a larger CC. 22 Our main objective in this study was to examine volumetric differences in the CC in children with 22q11DS in relationship to neuropsychological manifestations and specific functional singlenucleotide polymorphisms (SNPs) within the COMT (rs4680 or Val 158 Met ), ZDHHC8 (rs175174), PRODH (rs450046) and UFD1L (rs5992403) genes, within the corresponding 1.5-Mb interval of the 22q11.2 region.…”