A case-control study of brain structure and behavioral characteristics in 47,XXX syndrome.

Trisomy X, the presence of an extra X chromosome in females (47,XXX), is a relatively common but under-recognized chromosomal disorder associated with characteristic cognitive and behavioral features of varying severity. The objective of this study was to determine whether there were neuroanatomical differences in girls with Trisomy X that could relate to cognitive and behavioral differences characteristic of the disorder during childhood and adolescence. MRI scans were obtained on 35 girls with Trisomy X (mean age 11.4, SD 5.5) and 70 age- and sex-matched healthy controls. Cognitive and behavioral testing was also performed. Trisomy X girls underwent a semi-structured psychiatric interview. Regional brain volumes and cortical thickness were compared between the two groups. Total brain volume was significantly decreased in subjects with Trisomy X, as were all regional volumes with the exception of parietal gray matter. Differences in cortical thickness had a mixed pattern. The subjects with Trisomy X had thicker cortex in bilateral medial prefrontal cortex and right medial temporal lobe, but decreased cortical thickness in both lateral temporal lobes. The most common psychiatric disorders present in this sample of Trisomy X girls included anxiety disorders (40%), attention-deficit disorder (17%) and depressive disorders (11%). The most strongly affected brain regions are consistent with phenotypic characteristics such as language delay, poor executive function and heightened anxiety previously described in population-based studies of Trisomy X and also found in our sample.

Are there differences in brain morphometry between twins and unrelated singletons? A pediatric MRI study.

Twins provide a unique capacity to explore relative genetic and environmental contributions to brain development, but results are applicable to non-twin populations only to the extent that twin and singleton brains are alike. A reason to suspect differences is that as a group twins are more likely than singletons to experience adverse prenatal and perinatal events that may affect brain development. We sought to assess whether this increased risk leads to differences in child or adolescent brain anatomy in twins who do not experience behavioral or neurological sequelae during the perinatal period. Brain MRI scans of 185 healthy pediatric twins (mean age = 11.0, SD = 3.6) were compared to scans of 167 age- and sex-matched unrelated singletons on brain structures measured, which included gray and white matter lobar volumes, ventricular volume, and area of the corpus callosum. There were no significant differences between groups for any structure, despite sufficient power for low type II (i.e. false negative) error. The implications of these results are twofold: (1) within this age range and for these measures, it is appropriate to include healthy twins in studies of typical brain development, and (2) findings regarding heritability of brain structures obtained from twin studies can be generalized to non-twin populations.