Alterations in white matter pathways in Angelman syndrome

Dev Med Child Neurol. 2011 Apr;53(4):361-7. doi: 10.1111/j.1469-8749.2010.03838.x. Epub 2010 Dec 1.


Aim: Angelman syndrome is a neurogenetic disorder characterized by severe intellectual disability, absent speech, seizures, and outbursts of laughter. The aim of this study was to utilize diffusion tensor imaging (DTI) to examine alterations in white matter pathways in Angelman syndrome, with an emphasis on correlations with clinical severity.

Method: DTI was used to examine the arcuate fasciculus (AF), uncinate fasciculus (UF), inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFOF), and the corpus callosum (CC). We enrolled 14 children aged 8 to 17 years (mean age 10y 8mo; SD 2y 7mo) with Angelman syndrome (seven male; seven female) and 13 typically developing children, aged 8 to 17 years, for comparison (five male; eight female; mean age 12y; SD 2y 9mo). Individuals with Angelman syndrome were assessed using standardized measures of development, language, and behaviour.

Results: The children with Angelman syndrome exhibited lower fractional anisotropy and increased radial diffusivity values than the comparison group for the AF, UF, ILF, and CC (p < 0.006 corrected for multiple comparisons). They also had lower fractional anisotropy values for the IFOF and higher radial diffusivity values for the left IFOF (p < 0.006). Additionally, children with Angelman syndrome had significantly higher apparent diffusion coefficient values in the AF, CC, ILF, and the left IFOF (p < 0.006). Significant correlations were noted between DTI parameters and some of the clinical assessment outcomes (e.g. language, socialization, cognition) for three of the temporal pathways (AF, UF, ILF; p < 0.05).

Interpretation: Changes in DTI parameters in individuals with Angelman syndrome suggest decreased/delayed myelination, decreased axonal density or diameter, or aberrant axonal organization. Our findings suggest a generalized white matter alteration throughout the brain in those with Angelman syndrome; however, only the alterations in temporal white matter pathways were associated with language and cognitive and social functioning.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Analysis of Variance
  • Angelman Syndrome / genetics
  • Angelman Syndrome / pathology*
  • Anisotropy
  • Brain / pathology*
  • Child
  • Chromosomes, Human, Pair 15 / genetics
  • Corpus Callosum / pathology
  • Diffusion Tensor Imaging / methods
  • Female
  • Functional Laterality
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Nerve Fibers, Myelinated / pathology*
  • Neural Pathways / pathology*
  • Psychological Tests
  • Statistics as Topic