XXY (Klinefelter syndrome): A pediatric quantitative brain magnetic resonance imaging case-control study

OBJECTIVE. An extra X chromosome in males (XXY), known as Klinefelter syndrome, is associated with characteristic physical, cognitive, and behavioral features of variable severity. The objective of this study was to examine possible neuroana-tomical substrates of these cognitive and behavioral features during childhood and adolescence. METHODS. MRI brain scans were acquired for 42 XXY and 87 healthy XY age-matched control males. We compared these 2 groups on regional brain volumes and cortical thickness. RESULTS. Total cerebral volume and all lobar volumes except parietal white matter were significantly smaller in the XXY group, whereas lateral-ventricle volume was larger. Consistent with the cognitive profile, the cortex was significantly thinner in the XXY group in left inferior frontal, temporal, and superior motor regions. CONCLUSION. The brain-imaging findings of preferentially affected frontal, temporal, and motor regions and relative sparing of parietal regions are consistent with observed cognitive and behavioral strengths and weaknesses in XXY subjects.