Abnormal Language Pathway in Children With Angelman Syndrome

Abstract

Angelman Syndrome is a genetic disorder characterized by pervasive developmental disability with failure to develop speech. We examined the basis for severe language delay in Angelman Syndrome patients using diffusion tensor imaging. Magnetic Resonance Imaging/diffusion tensor imaging was performed in seven genetically confirmed Angelman Syndrome children (age:70±26 months, five males) and four age-matched controls to investigate the microstructural integrity of arcuate fasciculus and other major association tracts. Six of seven Angelman Syndrome children had unidentifiable left arcuate fasciculus while all controls had identifiable arcuate fasciculus. The right arcuate fasciculus was absent in six of seven Angelman Syndrome children and one of four controls. Diffusion tensor imaging color map suggested aberrant morphology of the arcuate fasciculus region. Other association tracts, including uncinate fasciculus, inferior-fronto-occipital fasciculus, inferior-longitudinal fasciculus, and corticospinal tract, were identifiable but showed decreased fractional anisotropy in Angelman Syndrome children. Increased apparent diffusion coefficient was seen in all tracts except uncinate fasciculus when compared to controls. Angelman Syndrome patients have global impairment of white matter integrity in association tracts, particularly, the arcuate fasciculus which shows severe morphological changes. This could be due to a potential problem with axon guidance during brain development possibly due to loss of UBE3A gene expression.

Autism spectrum disorder: neuropathology and animal models

“…Dendrites in layer III and V neurons of the visual cortex are shorter, less complex, and have fewer spines [176]. MRI and diffusion tensor imaging studies have revealed impaired white matter integrity in subjects with Angelman’s syndrome [281, 354, 388], likely due to a delay in myelination [146]. Similar to the observation of small brain size in human samples from Angelman’s syndrome, the total brain weight, as well as the weight of the cortex and cerebellum, is lower in a mouse model with maternal Ube3a deleted ( Ube3a m−/p+ ) [181].…”

Diffusion Tensor Imaging Studies on Arcuate Fasciculus in Stroke Patients: A Review

“…Diffusion tensor tractography (DTT), derived from DTI, allows for three-dimensional reconstruction and estimation of the AF (Catani et al, 2005; Nucifora et al, 2005; Glasser and Rilling, 2008). Therefore, DTI has been employed in many studies for evaluation of the AF in various brain pathologies, including stroke (Yamada et al, 2007; Breier et al, 2008, 2011; Hosomi et al, 2009; Rauschecker et al, 2009; Schlaug et al, 2009; Zhang et al, 2010; Kim et al, 2011; Kwon and Jang, 2011; Marchina et al, 2011; Song et al, 2011; Wilson et al, 2011; Kim and Jang, 2013; Kummerer et al, 2013; Yeatman and Feldman, 2013). …”

Relationship between aberrant brain connectivity and clinical features in Angelman Syndrome: A new method using tract based spatial statistics of DTI color-coded orientation maps

“…In an effort to relate brain anatomy to clinical phenotype in AS, our group(Wilson BJ et al, 2010; Wilson BJ et al, 2011)and subsequently others(Peters et al, 2011) have studied the major brain tracts using diffusion tensor imaging (DTI) with tractography and have shown very consistent abnormalities in various cortical association tracts, including the arcuate fasciculus thus accounting for the virtual absence of speech in these individuals.…”