ArticlePsychiatry research. Neuroimaging2025
Neuroanatomical alterations in young boys and adolescents with Klinefelter syndrome.
Article in Psychiatry research. Neuroimaging, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Klinefelter syndrome (KS, 47,XXY) is a common sex chromosome aneuploidy in males that is characterized by pubertal developmental delays and a wide range of alterations in cognitive, social and emotional functioning. The neural bases of these behavioral symptoms, however, are unclear. A total of 130 boys and adolescents, including 67 males with KS (11.5 ± 2.8 years) and 63 typically developing (TD; control) males (10.6 ± 2.8 years) underwent MRI scanning and pubertal assessment. Group differences in regional gray matter volume was examined using voxel-based morphometry while controlling for age at scan and total gray matter volume. Thresholded statistical significance maps indicated widespread reductions in frontal and temporal and cerebellar gray matter in males with KS relative to TD males, as well as increases in parietal and occipital gray matter. Secondary analyses explored potential associations between GMV in these regions and pubertal development. Lower testicular volume was a significant predictor of reduced GMV in frontal, temporal and cerebellar subregions, even after accounting for group status (KS, TD). Taken together, these findings add support for a neuroanatomical phenotype of KS and provide initial evidence for a role of pubertal development in KS-associated differences in gray matter structure. Future studies that examine the influence of testosterone supplementation on GMV in males with KS are warranted.
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