Aberrant white matter microstructure in children with 16p11.2 deletions
Julia P Owen1, Yi Shin Chang, Nicholas J Pojman
1Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California 94107, Program in Bioengineering, Department of Neurology, University of California, San Francisco, San Francisco, California 94158, Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, Simons Foundation, New York, New York 10010, Departments of Pediatrics and Medicine, Columbia University Medical Center, New York, New York 10032, and Center for Brain Science, Harvard University, Cambridge, Massachusetts 02138.
Children with 16p11.2 deletions show unique white matter changes, including increased axial diffusivity (AD), impacting cognition. These distinct microstructural alterations may explain cognitive impairments in this genetic condition.
Area of Science:
- Neuroimaging
- Genetics
- Developmental Neuroscience
Background:
- Copy number variants (CNVs) at the 16p11.2 locus, including deletions, are linked to neuropsychiatric disorders like autism and schizophrenia.
- Abnormal white matter microstructure is a common feature in these neurodevelopmental disorders.
Purpose of the Study:
- To investigate white matter microstructural integrity in children with 16p11.2 deletions using diffusion MRI.
- To correlate white matter alterations with cognitive function in deletion carriers.
Main Methods:
- Diffusion magnetic resonance imaging (dMRI) and tract-based spatial statistics (TBSS) were employed.
- Neurite orientation dispersion and density imaging (NODDI) was used for detailed microstructural analysis.
- Comparison between 16p11.2 deletion carriers and typically developing controls.
Main Results:
- Deletion carriers exhibited increased axial diffusivity (AD) in major white matter tracts (e.g., corpus callosum, internal/external capsules).
- Higher AD correlated with lower nonverbal IQ in deletion carriers.
- Distinct white matter alterations, including decreased fiber orientation dispersion, were observed, differing from other neurodevelopmental disorders.
Conclusions:
- 16p11.2 deletion is associated with a unique, widespread pattern of aberrant white matter microstructure.
- These microstructural changes may underlie the cognitive impairments observed in individuals with this CNV.
- The findings differentiate 16p11.2 deletion syndrome from other neurodevelopmental conditions with overlapping phenotypes.
