Charting Brain Structure in 22q11.2 Deletion Syndrome with Clinical Neuroimaging.

Area of Science:

• Neuroimaging
• Genetics
• Developmental Neuroscience

Background:

• 22q11.2 deletion syndrome (22q11DS) is a common genetic disorder associated with significant brain alterations and increased psychiatric risk.
• Existing research often excludes severely affected individuals, limiting understanding of neurobiological heterogeneity.
• Retrospective analysis of clinical MRI data offers a valuable approach to study brain structure in a broader 22q11DS population.

Purpose of the Study:

• To characterize brain structure deviations in 22q11DS using normative modeling.
• To develop 22q11DS-specific brain growth charts.
• To investigate the relationship between brain structure variations and cognitive outcomes in 22q11DS.

Main Methods:

• Utilized a cohort of 92 patients with 22q11DS and 252 matched controls.
• Applied normative modeling to calculate standardized deviation scores for brain imaging phenotypes.
• Correlated cortical deviations with gene expression data and developed syndrome-specific growth charts.

Main Results:

• Identified widespread brain deviations in 22q11DS, including reduced brain volumes and cortical surface area, and increased cortical thickness.
• Found significant convergence with existing ENIGMA-22q consortium data.
• Demonstrated that deviations from 22q11DS-specific growth charts correlate with cognitive outcomes, such as language scores.

Conclusions:

• Clinical MRI data can be effectively used to study brain structure in rare genetic disorders like 22q11DS.
• Syndrome-specific growth charts provide a novel method for quantifying within-syndrome variability.
• These growth charts hold prognostic value, linking individual brain structure to cognitive function.