Brain development in school-age and adolescent girls: Effects of Turner syndrome, estrogen therapy and genomic imprinting

Abstract Background The study of Turner syndrome offers a unique window of opportunity for advancing scientific knowledge of how X chromosome gene imprinting, epigenetic factors, hormonal milieu and chronologic age affects brain development in females. Methods Here, we describe brain growth trajectories in 55 girls with Turner syndrome (TS) and 53 typically developing (TD) girls (258 MR image datasets total) spanning 5 years. Using novel non-parametric and mixed effects analytic approaches we evaluate influences of X-chromosome genomic imprinting and hormone replacement therapy on brain development. Results Parieto-occipital gray and white matter regions show slower growth during typical pubertal timing in TS relative to TD girls. In contrast, some basal ganglia, cerebellar and limited cortical areas showed enhanced volume growth with peaks around 10 years of age. Conclusions The parieto-occipital finding suggests that girls with TS may be particularly vulnerable for altered brain development during adolescence. Basal ganglia regions may be relatively preserved in TS due to their maturational growth prior to, or early in typical pubertal years. Taken together, our findings indicate particular brain regions are more vulnerable to TS genetic and hormonal effects during puberty. These specific alterations in neurodevelopment may be more likely to affect long-term cognitive-behavioral outcomes in young girls with this common genetic condition.