Cerebral growth in Fragile X syndrome: review and comparison with Down syndrome

Neuroimaging studies have shown selective changes in brain size in Fragile X syndrome (FraX), which include reductions in the posterior cerebellar vermis, age-dependent increases in hippocampal volume, and enlarged caudate nucleus and thalamus. Contrasting with these limbic and subcortical anomalies, much less is known about the neocortex in FraX. The present study attempted to examine cerebral and lobar-level volumetric changes in young males with FraX (2-7 years), by comparing groups of subjects with full mutation (FM) and mosaicism (Mos) with both age-matched controls and subjects with developmental language delay (DLD) and Down syndrome (DS). For this purpose, we used high resolution (i.e, SPGR) MRI scans and semi-automated methods for segmenting (tissue class) and parcellating (i.e., Talairach) the brain. In agreement with previous studies, we found no changes in overall brain or cerebrum size in FraX. Nevertheless, boys with FM FraX had relative reductions in temporal lobe volume (primarily gray matter) and relative preservation/enlargement of parietal white matter volume. While temporal lobe reductions were not specific, since they were also observed in DLD and DS subjects, parietal preservation/enlargement was only seen in FraX. The relevance of these preliminary findings was emphasized by comparisons between FraX groups, which revealed more marked changes in FM FraX than in Mos FraX (i.e., gene dosage). While cross-sectional analyses revealed marked age-dependent decreases in DS, a group showing marked global and lobar volumetric reductions, there were no changes over time in FraX. These neuroimaging data are discussed in the context of FraX neurobiology and other developmental disorders.