Alterations in white matter pathways in Angelman syndrome
Open accessAbstract
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.
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MRI and diffusion tensor imaging studies have revealed impaired white matter integrity in subjects with Angelman syndrome, likely due to a delay in myelination.
“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].”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [281]
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- Authors
- PETERS, S. U., KAUFMANN, W. E., BACINO, C. A., ANDERSON, A. W., ADAPA, P., CHU, Z., YALLAMPALLI, R., TRAIPE, E., HUNTER, J. V., & WILDE, E. A.
- Affiliations
- Vanderbilt University (US)
- Kennedy Krieger Institute (US)
- Baylor College of Medicine (US)
- Corresponding author
- PETERS, SARIKA U
- ORCID
- Venue
- Developmental Medicine & Child Neurology
- Publisher
- Wiley
- Published
- 2010-12
- Volume
- 53
- Issue
- 4
- Pages
- 361-367
- ISSN
- 0012-1622 (ISSN-L)
- 1469-8749
- PMC
- PMC3059217
- OpenAlex
- W1584403666
- Cited by
- 69
- References
- 23
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 5 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 5 · 2019: 3 · 2018: 3 · 2017: 5 · 2016: 6 · 2015: 10 · 2014: 8 · 2013: 6 · 2012: 5
- FWCI
- 3.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Developmental Medicine & Child Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Angelman Syndrome Foundation
- National Institutes of Health (NIH U54, HD061222, RR019478)
- National Center for Research Resources (U54RR019478, RR-019478)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-061222, P30HD015052, U54HD061222)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- Angelman syndrome, white matter changes, arcuate fasciculus, uncinate fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, corpus callosum, fractional anisotropy, radial diffusivity, apparent diffusion coefficient, myelination, language development, intellectual disability, clinical severity
- MeSH terms
- Adolescent, Analysis of Variance, Brain, Child, Chromosomes, Human, Pair 15, Corpus Callosum, Female, Humans, Functional Laterality, Magnetic Resonance Imaging, Male, Nerve Fibers, Myelinated, Neural Pathways, Psychological Tests, Statistics as Topic, Anisotropy, Angelman Syndrome, Diffusion Tensor Imaging
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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