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.