Brain white matter abnormalities associated with copy number variants.

Area of Science:

• Neuroimaging
• Genetics
• Pediatric Neurology

Background:

• White matter (WM) signal abnormalities on brain MRI are observed in various neurodevelopmental disorders.
• Specific patterns of WM changes can assist in diagnosing these conditions.

Purpose of the Study:

• To characterize WM changes in microdeletion/microduplication syndromes.
• To identify common MRI patterns associated with these genetic conditions.

Main Methods:

• Retrospective analysis of brain MRIs from 13 pediatric patients with neurodevelopmental disorders and WM abnormalities.
• Blind interpretation of MRI scans by a pediatric neuroradiologist.
• Review of clinical and genetic data.

Main Results:

• Common findings included multifocal, periventricular WM signal abnormalities and WM volume loss.
• Dysgenesis of the corpus callosum was present in most patients (12/13).
• Clinical features frequently observed were global developmental delay, hypotonia, and epilepsy.

Conclusions:

• Chromosomal micro-rearrangement syndromes often present with similar, nonspecific MRI patterns of WM changes and corpus callosum dysgenesis.
• The presence of these MRI findings in children with global developmental delay should prompt consideration of chromosomal abnormalities.
• Chromosomal microarray analysis is recommended for diagnosing these conditions.