Brain structural alterations in young girls with Rett syndrome: A voxel-based morphometry and tract-based spatial statistics study

Abstract

Rett syndrome (RTT) is a neurodevelopmental disorder caused by loss-of-function variants in the MECP2 gene, currently with no cure. Neuroimaging is an important tool for obtaining non-invasive structural and functional information about the in vivo brain. Multiple approaches to magnetic resonance imaging (MRI) scans have been utilized effectively in RTT patients to understand the possible pathological basis. This study combined developmental evaluations with clinical severity, T1-weighted imaging, and diffusion tensor imaging, aiming to explore the structural alterations in cohorts of young girls with RTT, idiopathic autism spectrum disorder (ASD), or typical development. Voxel-based morphometry (VBM) was used to determine the voxel-wised volumetric characteristics of gray matter, while tract-based spatial statistics (SPSS) was used to obtain voxel-wised properties of white matter. Finally, a correlation analysis between the brain structural alterations and the clinical evaluations was performed. In the RTT group, VBM revealed decreased gray matter volume in the insula, frontal cortex, calcarine, and limbic/paralimbic regions; TBSS demonstrated decreased fractional anisotropy (FA) and increased mean diffusivity (MD) mainly in the corpus callosum and other projection and association fibers such as superior longitudinal fasciculus and corona radiata. The social impairment quotient and clinical severity were associated with these morphometric alterations. This monogenic study with an early stage of RTT may provide some valuable guidance for understanding the disease pathogenesis. At the same time, the pediatric-adjusted analytic pipelines for VBM and TBSS were introduced for significant improvement over classical approaches for MRI scans in children.

Evidence Synthesis of Gene Therapy and Gene Editing from Different Disorders—Implications for Individuals with Rett Syndrome: A Systematic Review

“…Unlike TSC, where there are apparent neuroanatomical signs, whether this approach would be feasible for individuals with RTT is unclear. In a study of 28 girls with RTT (mean age (years) ± SD: 3.5 ± 1.25 years), MRI revealed structural brain abnormalities such as decreased grey matter in the insula, frontal cortex and limbic regions [97]. Diffusion MRI of Rett brains may also allow for finer details of brain microstructure to be revealed at various stages of development [98].…”

Metformin Induces MeCP2 in the Hippocampus of Male Mice with Sex-Specific and Brain-Region-Dependent Molecular Impact

“…Mice from all experimental groups were euthanized at P49 and the liver and 4 brain regions (frontal cortex, cerebellum, thalamus, and hippocampus) were dissected as previously reported [17]. These selected brain regions have been reported to contribute to RTT symptoms and/or mechanism of disease, including the frontal cortex [18], cerebellum [19], thalamus [20], and hippocampus [21].…”