Abstract
Background
Turner syndrome (TS) and Noonan syndrome (NS) are distinct genetic conditions with
highly similar physical and neurodevelopmental phenotypes. TS is caused by X chromosome
absence, whereas NS results from genetic mutations activating the Ras–mitogen-activated
protein kinase signaling pathway. Previous neuroimaging studies in individuals with
TS and NS have shown neuroanatomical variations relative to typically developing individuals,
a standard comparison group when initially examining a clinical group of interest.
However, none of these studies included a second clinical comparison group, limiting
their ability to identify syndrome-specific neuroanatomical phenotypes.
Methods
In this study, we compared the behavioral and brain phenotypes of 37 girls with TS,
26 girls with NS, and 37 typically developing girls, all ages 5 to 12 years, using
univariate and multivariate data-driven analyses.
Results
We found divergent neuroanatomical phenotypes between groups, despite high behavioral
similarities. Relative to the typically developing group, TS was associated with smaller
whole-brain cortical surface area (p ≤ .0001), whereas NS was associated with smaller whole-brain cortical thickness (p = .013). TS was associated with larger subcortical volumes (left amygdala, p = .002; right hippocampus, p = .002), whereas NS was associated with smaller subcortical volumes (bilateral caudate,
p ≤ .003; putamen, p < .001; pallidum, p < .001; right hippocampus, p = .015). Multivariate analyses also showed diverging brain phenotypes in terms of
surface area and cortical thickness, with surface area outperforming cortical thickness
at group separation.
Conclusions
TS and NS have syndrome-specific brain phenotypes, despite their behavioral similarities.
Our observations suggest that neuroanatomical phenotypes better reflect the different
genetic etiologies of TS and NS and may be superior biomarkers relative to behavioral
phenotypes.
Keywords
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Article info
Publication history
Published online: September 06, 2022
Accepted:
August 25,
2022
Received in revised form:
July 20,
2022
Received:
April 11,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
