Surface‐based morphometry reveals distinct cortical thickness and surface area profiles in Williams syndrome

Abstract

Morphometric investigations of brain volumes in Williams syndrome (WS) consistently show significant reductions in gray matter volume compared to controls. Cortical thickness (CT) and surface area (SA) are two constituent parts of cortical gray matter volume that are considered genetically distinguishable features of brain morphology. Yet, little is known about the independent contribution of cortical CT and SA to these volumetric differences in WS. Thus, our objectives were: (i) to evaluate whether the microdeletion in chromosome 7 associated with WS has a distinct effect on CT and SA, and (ii) to evaluate age-related variations in CT and SA within WS. We compared CT and SA values in 44 individuals with WS to 49 age- and sex-matched typically developing controls. Between-group differences in CT and SA were evaluated across two age groups: young (age range 6.6-18.9 years), and adults (age range 20.2-51.5 years). Overall, we found contrasting effects of WS on cortical thickness (increases) and surface area (decreases). With respect to brain topography, the between-group pattern of CT differences showed a scattered pattern while the between-group surface area pattern was widely distributed throughout the brain. In the adult subgroup, we observed a cluster of increases in cortical thickness in WS across the brain that was not observed in the young subgroup. Our findings suggest that extensive early reductions in surface area are the driving force for the overall reduction in brain volume in WS. The age-related cortical thickness findings might reflect delayed or even arrested development of specific brain regions in WS.

PTPN11 Gain-of-Function Mutations Affect the Developing Human Brain, Memory, and Attention

“…One possible explanation for these differential effects is that distinct genetic influences control SA and CT development (Panizzon et al 2009;Rimol et al 2010;Winkler et al 2010). Moreover, this pattern of increased CT and decreased SA has been reported in other neurogenetic conditions such as Williams syndrome (Green et al 2016), 22q11.2 deletion syndrome (Schmitt et al 2001), TS (Lepage et al 2013), and Down syndrome (Lee et al 2015). Of note, such differences were not reported in Neurofibromatosis 1 (Violante et al 2013).…”

Abnormal Cortical Thickness Is Associated With Deficits in Social Cognition in Patients With Myotonic Dystrophy Type 1

“…In particular, we found both positive and negative correlations between CTG triplet expansion size and cortical thickness. In several genetic conditions, such as Down syndrome (38), Williams syndrome (39), and Prader-Willi syndrome (40), but also in neurodevelopmental disorders such as autism (41), both increased and decreased gray matter volumes were found. In these studies, compensation brain mechanisms were hypothesized.…”

White matter alterations in Williams syndrome related to behavioral and motor impairments

“…Individuals with WS were found to have less average gray and WM volume in several brain regions, as well as some areas with significant volume increase (Figure 2) (Campbell et al, 2009; Green et al, 2016).…”