Abstract
Rett syndrome (RTT) is a rare neurodevelopmental disorder characterized by severe cognitive, social, and physical impairments resulting from de novo mutations in the X-chromosomal methyl-CpG binding protein gene 2 (MECP2). While there is still no cure for RTT, exploring up-to date neurofunctional diagnostic markers, discovering new potential therapeutic targets, and searching for novel drug efficacy evaluation indicators are fundamental. Multiple neuroimaging studies on brain structure and function have been carried out in RTT-linked gene mutation carriers to unravel disease-specific imaging features and explore genotype-phenotype associations. Here, we reviewed the neuroimaging literature on this disorder. MRI morphologic studies have shown global atrophy of gray matter (GM) and white matter (WM) and regional variations in brain maturation. Diffusion tensor imaging (DTI) studies have demonstrated reduced fractional anisotropy (FA) in left peripheral WM areas, left major WM tracts, and cingulum bilaterally, and WM microstructural/network topology changes have been further found to be correlated with behavioral abnormalities in RTT. Cerebral blood perfusion imaging studies using single-photon emission CT (SPECT) or PET have evidenced a decreased global cerebral blood flow (CBF), particularly in prefrontal and temporoparietal areas, while magnetic resonance spectroscopy (MRS) and PET studies have contributed to unraveling metabolic alterations in patients with RTT. The results obtained from the available reports confirm that multimodal neuroimaging can provide new insights into a complex interplay between genes, neurotransmitter pathway abnormalities, disease-related behaviors, and clinical severity. However, common limitations related to the available studies include small sample sizes and hypothesis-based and region-specific approaches. We, therefore, conclude that this field is still in its early development phase and that multimodal/multisequence studies with improved post-processing technologies as well as combined PET–MRI approaches are urgently needed to further explore RTT brain alterations.
Highlights
The postnatal stage is a significantly dynamic brain growth and development period characterized by both macrostructural and microstructural changes
We have summarized a few imaging literature studies on Rett syndrome (RTT) with methyl-CpG binding protein gene 2 (MECP2) mutations and compared various imaging modalities to clarify their strengths and weaknesses (Table 2)
We have attempted to summarize the findings from the conducted MRI to PET studies over the past few decades on RTT with MECP2 mutations
Summary
The postnatal stage is a significantly dynamic brain growth and development period characterized by both macrostructural and microstructural changes. As a severe neurological disease, Rett syndrome (RTT) leads to neurodevelopmental abnormalities in this crucial period, primarily arising from de novo mutations in the X-chromosomal methyl-CpG binding protein gene 2 (MECP2) [3–5]. The application of neuroimaging to RTT has been explored for decades. Various imaging techniques have been used to answer the fundamental questions about the biological basis of RTT and to characterize in vivo disease pathology. Neuroimaging studies on RTT provide essential insights into anatomical, functional, metabolic, and dynamic changes in the brain reflecting the biological effects of MECP2 mutations and allow to monitor future therapeutic outcomes. The present article reviews the current applications of multimodal neuroimaging to RTT and provides potential future directions in this field
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
