Neurodevelopment of Williams Syndrome Williams

Neurodevelopment of Williams Syndrome

Williams Syndrome is a genetic neurodevelopmental disorder that is rare and is only recently being understood by science. is a genetic neurodevelopmental disorder that is rare and occurs in only one in 7,500 live births. This condition stems from a deletion, or genetic aberration which results in a missing hormone, on chromosome 7q11.23 and causes the individual to display physical and neuropsychological profile characteristics. Also included in the gene deletion is gene ELN, which is the gene responsible for coding important elastic protein, elastin, in connective tissues that are especially present in the larger blood vessels in the body such as the aorta. According to Bellugi et al. (2007) "Language represents a relative strength compared to other intellectual abilities. Within visual cognition, face recognition appears remarkably 'spared', whereas other aspects of visual-spatial functioning are severely impaired." The work of Chiang et al. (2007) informs this study that in WS: "...occipital areas, parietal lobe regions close to the temporo-pariental junction, the splenium and posterior body of the corpus callosum, thalamus and basal ganglia and midbrain were disproportionately reduced." This study is informed by the work of Bhattacharjee (2005) that since researchers and scientists discovered in the early part of the 1990s decade that WS is caused by a deletion of partial section of one copy of chromosome 7 that there has been an attempt to identify the roles that different genes within that specific section play in brain development and functioning. Bhattacharjee relates that: "The uniform and well-defined cognitive features shared by those with WS have convinced some researchers that the disorder offers a window into the genetic basis of the human mind." (2007)

NEURODEVELOPMENT of WILLIAMS SYNDROME

STATEMENT of PROBLEM

Williams Syndrome is a genetic neurodevelopmental disorder that is rare and is only recently being understood by science. Recent studies have shown that brain volume differences exist in WS patients and normally developed individuals.

INTRODUCTION

Williams Syndrome (WS) is a genetic neurodevelopmental disorder that is rare and occurs in only one in 7,500 live births. This condition stems from a deletion, or genetic aberration which results in a missing hormone, on chromosome 7q11.23 and causes the individual to display physical and neuropsychological profile characteristics. Also included in the gene deletion is gene ELN, which is the gene responsible for coding important elastic protein, elastin, in connective tissues that are especially present in the larger blood vessels in the body such as the aorta. Individuals with Williams syndrome generally have cardiac abnormalities of a specific nature, hypersensitivity to sound and facial features characteristic of this syndrome. Mild to moderate intellectual impairments are experienced by those with Williams syndrome and even more pronounced impairments in terms of performance than in terms of the verbal IQ.

I. AFFECT, SOCIAL BEHAVIOR and PERSONALITY CHARACTERISTICS of WS

Williams Syndrome has been the focus of a twenty-year program of research conducted and reported in the work of Bellugi et al. (2007) entitled: "Affect, Social Behavior, and the Brain in Williams Syndrome" which relates that this program of research "has outlined an unusual profile of cognitive dissociations in WS: Language represents a relative strength compared to other intellectual abilities. Within visual cognition, face recognition appears remarkably 'spared', whereas other aspects of visual-spatial functioning are severely impaired." Bellugi et al. state that the characterizations of Williams Syndrome personality include: "...hypersociability, including overfriendliness and heightened approachability toward others, combined with anxiety relating to new situations and objects and a difficulty in forming and maintaining friendships with peers." (2007) it is related by Bellugi et al. that the language proficiency of individuals with WS often impresses strangers. Bellugi et al. (2007) reports that the work of Losh, Bellugi, Reilly and Anderson (2000) "...asked 30 children with WS and a typically developing control group matched for gender and chronological age (4-12) to tell a story from the wordless picture book 'Frog, Where Are You?'. The transcribed stories were coded separately for grammar and for the social and affective use of language" (2007) and specifically for evaluative language which is stated to refer "...to language reflecting the narrator's attitude or perspective, including attributing emotions or motivations to characters using intensifiers (really, very, so) and sound effects, direct quotes and character speed. A new category called 'audience hookers' referring to other devices to capture and maintain the listener's attention was developed for the evaluative-language coding system to characterize a language function unique to WS. " (2007) Results show that while the WS individuals made more grammatical errors than did their typical peers in terms of evaluative devices "their stories contained significantly more social and affective evaluative devices." (Bellugi, et al., 2007)

Frequency of Social-Evaluation Devices

Source: Bellugi et al. (2007)

II. BRAIN DIFFERENCES in INDIVIDUALS WITH WS

The work of Buattacharjee (2005) entitled: "Friendly Faces and Unusual Minds" published in the Journal of Science states that: "The uniform and well-defined cognitive features shared by those with WS have convinced some researchers that the disorder offers a window into the genetic basis of the human mind. Since the discovery in the early 1990s that the syndrome is caused by the deletion of a tiny section of one copy of chromosome 7, researchers have attempted the syndrome is caused by the deletion of a tiny section of one copy of chromosome 7, researchers that have attempted to identify the roles that are the different genes within that section play in the development and functioning of the brain." (Bhattacharjee, 2005)

The work of Ming-Chang Chiang et al. (2007) entitled: "3D Pattern of Brain Abnormalities in Williams Syndrome Visualized Using Tenor-Based Morphometry" states that a study was conducted through application of tenor-based morphometry (TBM) for the detection and automatic quantification of "...subtle and distributed patterns of brain volume differences between 41 WS and 39 normal subjects." Chiang et al. states that in the TBM approach "all images were nonlinearly deformed to match a preselected brain image, which acts as a template. Then, the Jacobian determinant" or the local expansion factors "of the deformation fields is used to gauge the local volume differences between the individual images and the template, and these can be analyzed statistically to identify group differences or localized volume increases or reductions at the voxel level." (Chiang, et al. 2007) Images derived from this study are shown in the following figure.

Brain (Left to Right) Highest TQS (a WS subject), the lowest TQS (a control subject)

Source: Chiang et al. (2007)

Results of the study show that the "total brain volume was 13% smaller in WS than control subjects. Voxelwise comparison was conducted and the study states findings that "in WS subjects, the volume of prefrontal and orbito-frontal areas, the anterior cingulate gyrus, inferior parietal regions at the parieto-occipital junction, the superior temporal gyrus, amygdale and part of the hippocampus (generally on the right side), fusiform gyrum, and cerebellum were relatively preserved. However occipital areas, parietal lobe regions close to the temporo-pariental junction, the splenium and posterior body of the corpus callosum, thalamus and basal ganglia and midbrain were disproportionately reduced in WS." (Chiang, 2007)

The work of Schultz (2001) entitled: "Genetics of Childhood Disorders: XXVI. Williams Syndrome and Brain -- Behavior Relationships" published in the Journal of the American Academy of Child and Adolescent Psychiatry relates that recent magnetic resonance imaging (MRI) morphometric evidence provides a possible physiological basis for strengths in language and also for the heightened interest in music, and, in some cases, savant-like musical skill. Despite brain volumes that are about 15% smaller than normal, the superior temporal gyrus, an area that encompasses primary auditory cortex and association regions important for the elaboration of auditory inputs necessary for both language and music processing, is approximately normal volume in people with WS." (Schultz, 2001) There have not been thus far any published functional neuroimaging studies in WS. According to Schultz (2001) "Alterations of function in this brain region may subserve the high rate of hyperacusis in WS and could also be related to language and music perceptual processes. In addition, preliminary structural MRI evidence suggests an exaggerated leftward asymmetry of the planum temporale, a cortical region buried in the depth of the sylvian fissure along the posterior aspect of the superior temporal gyrus. A leftward asymmetry of planum temporale has been linked to normal hemispheric dominance for language, and in musicians with perfect pitch there appears to be even more pronounced leftward asymmetry of this region than is typical. The associations between language, music, and superior aspects of the temporal lobe may be just one of many examples of this nature in the brains of people with WS. A more general hypothesis is that variations in the integrity of diverse brain regions, each with discrete functions within larger networks, provide the physiological bases for the specific strengths and weaknesses in WS." (Schultz, 2001) Schultz (2001) states that converging evidence exists that "the WS brain is a mosaic of spared and affected systems and that the patterns of spared and affected brain networks will correlate and predict the WS cognitive and social-affective profile. This not only serves as a model for understanding the functional and structural independence of discrete brain systems, but as more is learned about the function of genes in the WS critical region, there is the promise of being able to delineate the ontological progression of genes to brain organization to phenotypic function." (Schultz, 2001)