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 (RAS-MAPK) signaling pathway. Previous neuroimaging studies in TS and
NS have shown neuroanatomical variations relative to typically developing (TD) 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 TD girls, all 5–12 years of age, using univariate and multivariate
data-driven analyses.
Results
We found divergent neuroanatomical phenotypes between groups, despite high behavioral
similarities. TS was associated with smaller whole-brain cortical surface area (SA)
(p=<0.0001) whereas NS was associated with smaller whole-brain cortical thickness
(CT) (p=.013) relative to TD. TS was associated with larger subcortical volumes (left amygdala,
p=0.002; right hippocampus, p=0.002) whereas NS was associated with smaller subcortical volumes (bilateral caudate,
p0.003; putamen, p<0.001; pallidum, p<0.001; right hippocampus, p=0.015). Multivariate analyses also showed diverging brain phenotypes in terms of SA
and CT, with SA outperforming CT at group separation.
Conclusion
TS and NS have syndrome-specific brain phenotypes, despite their behavioral similarities.
Our observations suggest that neuroanatomical phenotypes better reflect the different
genetics etiologies of TS and NS and may be superior biomarkers relative to behavioral
phenotypes.
Key words
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Article Info
Publication History
Accepted:
August 25,
2022
Received in revised form:
July 20,
2022
Received:
April 11,
2022
Publication stage
In Press Journal Pre-ProofFootnotes
Conflict of interest statement: All authors report no biomedical financial interests or potential conflicts of interest.
Identification
Copyright
© 2022 Published by Elsevier Inc on behalf of Society of Biological Psychiatry.
