Influence of X Chromosome and Hormones on Human Brain Development: A Magnetic Resonance Imaging and Proton Magnetic Resonance Spectroscopy Study of Turner Syndrome

Background Women with Turner syndrome (TS; 45,X) lack a normal second X chromosome, and many are prescribed exogenous sex and growth hormones (GH). Hence, they allow us an opportunity to investigate genetic and endocrine influences on brain development. Methods We examined brain anatomy and metabolism in 27 adult monosomic TS women and 21 control subjects with volumetric magnetic resonance imaging and magnetic resonance spectroscopy. Results In TS women, regional gray matter volume was significantly smaller in parieto-occipital cortex and caudate nucleus and larger in cerebellar hemispheres. White matter was reduced in the cerebellar hemispheres, parieto-occipital regions, and splenium of the corpus callosum but was increased in the temporal and orbitofrontal lobes and genui of corpus callosum. Women with TS had a significantly lower parietal lobe concentration of N-acetyl aspartate, and higher hippocampal choline. Also, among women with TS, there were significant differences in regional gray matter volumes and/or neuronal integrity, depending upon parental origin of X chromosome and oxandrolone and GH use. Conclusions X chromosome monosomy, imprinting and neuroendocrine milieu modulate human brain development—perhaps in a regionally specific manner.