ORIGINAL RESEARCH n NEURORADIOLOGY Radiology: Volume 286: Number 1—January 2018 n radiology.rsna.org 217 1 From the Departments of Radiology (J.P.O., O.A.G., S.S.N., P.M.) and Neurology (P.B., N.P., T.T., E.H.S.), University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA 94158; Department of Biostatistics, Columbia University, New York, NY (Q.C., J.L., D.D.); Department of Medicine and Pediatrics, Baylor School of Medicine, Houston, Tex (J.V.H.); Department of Radiology, Children’s Hospital of Philadelphia, Philadelphia, Pa (J.I.B., T.P.R.); and Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, Mass (R.B.). Received December 23, 2016; revision requested February 21, 2017; revision received April 20; accepted May 5; final version accepted May 12. Address correspondence to E.H.S. (e-mail: sherre@ neuropeds.ucsf.edu). 2 Current address: Department of Radiology, University of Washington, Seattle, Wash. Study supported by Simons Foundation (SFARI A118077). q RSNA, 2017 Purpose: To identify developmental neuroradiologic findings in a large cohort of carriers who have deletion and duplication at 16p11.2 (one of the most common genetic causes of autism spectrum disorder [ASD]) and assess how these features are associated with behavioral and cognitive outcomes. Materials and Methods: Seventy-nine carriers of a deletion at 16p11.2 (referred to as deletion carriers; age range, 1–48 years; mean age, 12.3 years; 42 male patients), 79 carriers of a duplication at 16p11.2 (referred to as duplication carriers; age range, 1–63 years; mean age, 24.8 years; 43 male patients), 64 unaffected family members (referred to as familial noncarriers; age range, 1–46 years; mean age, 11.7 years; 31 male participants), and 109 population control participants (age range, 6–64 years; mean age, 25.5 years; 64 male participants) were enrolled in this cross-sectional study. Participants underwent structural mag- netic resonance (MR) imaging and completed cognitive and behavioral tests. MR images were reviewed for development- related abnormalities by neuroradiologists. Differences in frequency were assessed with a Fisher exact test corrected for multiple comparisons. Unsupervised machine learning was used to cluster radiologic features and an association between clusters and cognitive and behavioral scores from IQ testing, and parental measures of development were tested by using analysis of covariance. Volumetric analysis with automated seg- mentation was used to confirm radiologic interpretation. Results: For deletion carriers, the most prominent features were dys- morphic and thicker corpora callosa compared with familial noncarriers and population control participants (16%; P , .001 and P , .001, respectively) and a greater likelihood of cerebellar tonsillar ectopia (30.7%; P , .002 and P , .001, re- spectively) and Chiari I malformations (9.3%; P , .299 and P , .002, respectively). For duplication carriers, the most salient findings compared with familial noncarriers and population control participants were reciprocally thinner corpora callosa (18.6%; P , .003 and P , .001, respectively), decreased white matter volume (22.9%; P , .001, and P , .001, respectively), and increased ventricular volume (24.3%; P , .001 and P , .001, respectively). By comparing cognitive assessments to im- aging findings, the presence of any imaging feature associated with deletion carriers indicated worse daily living, communica- tion, and social skills compared with deletion carriers without any radiologic abnormalities (P , .005, P , .002, and P , .004, respectively). For the duplication carriers, presence of decreased white matter, callosal volume, and/or increased ven- tricle size was associated with decreased full-scale and verbal IQ scores compared with duplication carriers without these findings (P , .007 and P , .004, respectively). Conclusion: In two genetically related cohorts at high risk for ASD, re- ciprocal neuroanatomic abnormalities were found and de- termined to be associated with cognitive and behavioral impairments. q RSNA, 2017 Online supplemental material is available for this article. Julia P. Owen, PhD 2 Polina Bukshpun, BA Nicholas Pojman, BS Tony Thieu, MS Qixuan Chen, PhD Jihui Lee, MS Debra D’Angelo, MS Orit A. Glenn, MD Jill V. Hunter, MD Jeffrey I. Berman, PhD Timothy P. Roberts, PhD Randy Buckner, PhD Srikantan S. Nagarajan, PhD Pratik Mukherjee, MD, PhD Elliott H. Sherr, MD, PhD Brain MR Imaging Findings and Associated Outcomes in Carriers of the Reciprocal Copy Number Variation at 16p11.2 1 This copy is for personal use only. To order printed copies, contact reprints@rsna.org