Adolescent brain development in girls with Turner syndrome

• Published in: Human brain mapping 2023-07, Vol.44 (10), p.4028-4039
• Main Authors: Lozano Wun, Vanessa, Foland‐Ross, Lara C., Jo, Booil, Green, Tamar, Hong, David, Ross, Judith L., Reiss, Allan L.
• Format: Article
• Language: English
• Subjects: Adolescents; Amygdala; Aneuploidy; Brain; Brain - diagnostic imaging; Chromosomes; Cognitive ability; Estrogens; Female; Genetic disorders; Girls; gray matter; Gray Matter - diagnostic imaging; Haploinsufficiency; Hormonal effects; Humans; Magnetic Resonance Imaging; Monosomy; neurodevelopment; Phenotypes; puberty; sex chromosome; Sex chromosomes; Substantia grisea; Surface area; Temporal lobe; Thickness; Turner syndrome; Turner Syndrome - diagnostic imaging; Turner Syndrome - psychology; Turner's syndrome
• ISSN: 1065-9471; 1097-0193
• DOI: 10.1002/hbm.26327

Turner syndrome (TS) is a common sex chromosome aneuploidy in females associated with various physical, cognitive, and socio‐emotional phenotypes. However, few studies have examined TS‐associated alterations in the development of cortical gray matter volume and the two components that comprise this measure—surface area and thickness. Moreover, the longitudinal direct (i.e., genetic) and indirect (i.e., hormonal) effects of X‐monosomy on the brain are unclear. Brain structure was assessed in 61 girls with TS (11.3 ± 2.8 years) and 55 typically developing girls (10.8 ± 2.3 years) for up to 4 timepoints. Surface‐based analyses of cortical gray matter volume, thickness, and surface area were conducted to examine the direct effects of X‐monosomy present before pubertal onset and indirect hormonal effects of estrogen deficiency/X‐monosomy emerging after pubertal onset. Longitudinal analyses revealed that, whereas typically developing girls exhibited normative declines in gray matter structure during adolescence, this pattern was reduced or inverted in TS. Further, girls with TS demonstrated smaller total surface area and larger average cortical thickness overall. Regionally, the TS group exhibited decreased volume and surface area in the pericalcarine, postcentral, and parietal regions relative to typically developing girls, as well as larger volume in the caudate, amygdala, and temporal lobe regions and increased thickness in parietal and temporal regions. Surface area alterations were predominant by age 8, while maturational differences in thickness emerged by age 10 or later. Taken together, these results suggest the involvement of both direct and indirect effects of X‐chromosome haploinsufficiency on brain development in TS. Surface‐based analyses of cortical gray matter volume, thickness, and surface area were conducted using an accelerated longitudinal design in girls ages 4–17 years with Turner syndrome (TS; 45, XO) and typical development (TD). Statistical analyses revealed that whereas TD girls exhibited normative declines in gray matter structure throughout adolescence, this pattern was reduced or inverted in girls with TS. Findings suggest the involvement of both direct and indirect effects of the X‐chromosome on brain development.