Altered Brain Structure in Infants with Turner Syndrome

Turner syndrome (TS) is a genetic disorder affecting approximately 1:2000 live-born females. It results from partial or complete X monosomy and is associated with a range of clinical issues including a unique cognitive profile and increased risk for certain behavioral problems. Structural neuroimaging studies in adolescents, adults, and older children with TS have revealed altered neuroanatomy but are unable to identify when in development differences arise. In addition, older children and adults have often been exposed to years of growth hormone and/or exogenous estrogen therapy with potential implications for neurodevelopment. The study presented here is the first to test whether brain structure is altered in infants with TS. Twenty-six infants with TS received high-resolution structural MRI scans of the brain at 1 year of age and were compared to 47 typically developing female and 39 typically developing male infants. Results indicate that the typical neuroanatomical profile seen in older individuals with TS, characterized by decreased gray matter volumes in premotor, somatosensory, and parietal-occipital cortex, is already present at 1 year of age, suggesting a stable phenotype with origins in the prenatal or early postnatal period

Early Abnormalities in Social, Attentional, and Working Memory Circuits in Infants with Turner Syndrome

pp. 1962–1971 of this journal issue entitled: Proceedings from the Turner Resource Network symposium: The crossroads of health care research and health care deliveryAdults and children with Turner syndrome differ from typical female individuals with 46,XX karyotype in key components of neural circuits for social cognition and working memory. Specifically, imaging studies demonstrate reductions in somatosensory cortex and inferior parietal lobule, enlargement of the amygdalae and insular and orbitofrontal cortex, altered white matter microstructure and disrupted frontoparietal circuitry in women with Turner syndrome. Altered activation of the amygdala and caudate during cognitive tasks also has been reported. What is not known is when in development these relationships arise. This knowledge gap is important, as it limits our ability to determine the appropriate type and timing of behavioral interventions and hormone therapies. Imaging of infants with Turner syndrome showed decreased gray matter volumes in parietal cortex and increased gray matter volumes in insular cortex when compared to female controls, consistent with findings in older children. This suggests a stable phenotype, with origins in the prenatal or early postnatal period. Infants with Turner syndrome did not exhibit widespread changes in white matter microstructure that have been reported in older children, suggesting that early interventions might prevent or ameliorate atypical white matter development in Turner syndrome. At 1 year of age, functional connectivity maps revealed reduced fronto-parietal connectivity in infants with Turner syndrome, and increased connectivity with the insula. At age 2, functional connectivity maps revealed a lack of typical connectivity between caudate and frontal lobe in infants with Turner syndrome. Extensive negative correlations with middle temporal gyrus were present in infants with Turner syndrome, but not in controls. Additional studies are needed to examine longitudinal changes in brain structure and function in Turner syndrome, relate clinical variables (such as genetic and hormonal variation) to brain development, and test whether individual variation in neuroimaging phenotypes predicts cognitive outcomes

The impact of X-chromosome loss on brain structure and function in infancy

Session 12 - The X chromosome in neurodevelopmental disordersMany childhood-onset behavioral disorders are male-biased, including autism spectrum disorders, attention-deficit hyperactivity disorder, and early onset persistent antisocial behavior. It has been hypothesized that these differences result from sex chromosome effects on the development of brain structure and function. Behavioral and neuroimaging studies of individuals with partial or complete X monosomy (Turner Syndrome or TS) provide an unparalleled opportunity to test this hypothesis. However, all studies of TS to date have been carried out in adults and older children. The study presented here is the first to test whether brain structure and function is altered in infants with TS. Our central hypothesis was that infants with TS would show altered gray matter volumes, anatomical connectivity, and functional connectivity in the neural circuits for social cognition and executive function. High-resolution structural magnetic resonance imaging revealed that infants with TS had decreased gray matter volumes in parietal cortex and increased gray matter volumes in insular cortex compared to XX females. Findings are highly similar to neuroanatomical studies of older children with TS, suggesting a stable phenotype with origins in the prenatal or early postnatal period. Diffusion tensor imaging (DTI) revealed that infants with TS did not exhibit the extensive reductions in FA seen in older children, but did show focal reductions in FA in several regions, suggesting that global reductions in FA arise after two years of age. Resting state functional connectivity analyses suggested reduced fronto-parietal connectivity in infants with TS, a lack of typical connectivity between caudate and frontal lobe, and increased connectivity with the insula. Results provide new insight into the impact of X-chromosome loss on neurodevelopment in early life