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

作者：Benjamin Jung, J. Eric Schmitt, Jakob Seidlitz, Jenna Schabdach, Shivaram Karandikar, T. Blaine Crowley, Lena Dorfschmidt, Ayan S. Mandal, Dabriel Zimmerman, Remo Williams, Smrithi Prem, Elizabeth Levitis, Margaret Gardner, K. Cyr, Viveknarayanan Padmanabhan, Jerome H. Taylor, Kosha Ruparel, Rune Bøen, Carrie E. Bearden, Christopher R. K. Ching, Bogdan Paşaniuc, Stewart A. Anderson, Daniel E. McGinn, Elaine H. Zackai, Beverly S. Emanuel, Sarah Hopkins, Madeline Chadehumbe, Karen Low, Tim Cole, Richard A. I. Bethlehem, Russell T. Shinohara, J. William Gaynor, David R. Roalf, Raquel E. Gur, Donna M. McDonald‐McGinn, Aaron Alexander‐Bloch · 发表于：medRxiv · 年份：2025 · DOI：10.1101/2025.11.25.25339898 · 被引用次数：2 · 研究领域：Congenital heart defects research、Williams Syndrome Research、Fetal and Pediatric Neurological Disorders

Background: 22q11.2 deletion syndrome (22q11DS) is a common microdeletion associated with widespread brain alterations and elevated risk for schizophrenia and other neuropsychiatric conditions. Prospective research studies often exclude individuals with severe cognitive impairment, medical comorbidities, or inability to tolerate research MRI without sedation, features common in 22q11DS. This limits both the generalizability of neuroimaging findings and our understanding of the full phenotypic spectrum. Moreover, while standard brain growth charts quantify deviation from typical development, they cannot identify patients who are disproportionately affected relative to their genetic peers, limiting clinical utility for risk stratification. Leveraging clinical MRI data offers a scalable approach to address these gaps. Methods: We analyzed 92 patients with 22q11DS (age 0.5-21 years, 49% female) and 252 matched clinical controls. Using normative modeling derived from 1,995 reference clinical scans, we quantified individual-level brain deviations from population norms. We validated clinical findings against the independent ENIGMA-22q research consortium, characterized rates of extreme structural deviations to assess within-syndrome heterogeneity, correlated spatial patterns of brain alterations with gene expression from the Allen Human Brain Atlas, and generated syndrome-specific growth charts to test whether deviations from syndrome-specific norms predicted cognitive and language ...