Rett Syndrome Study Finds Brain Changes Before Symptoms Begin

Researchers at Texas Children's Hospital's Duncan Neurological Research Institute and Baylor College of Medicine have identified early brain-cell changes in mouse models of Rett syndrome before visible symptoms appear, offering a clearer window into how the rare genetic neurological disorder begins. The study, published in Science Advances, focused on the effects of MECP2 mutations, which disrupt how genes are regulated in brain cells and are the main cause of Rett syndrome, a condition that mostly affects girls and can lead to loss of speech, purposeful hand movement, motor control and social engagement after early infancy. By studying brain cells before disease signs emerged, the researchers found a core group of dysfunctional genes involved in communication between neurons, suggesting that disrupted synaptic signalling may be one of the earliest steps in the disease process. They also identified vulnerable brain-cell types, including specialised hippocampal interneurons, that appear especially sensitive to MECP2 malfunction, while even genetically normal neighbouring cells showed changes in gene activity because of the surrounding diseased environment. The discovery is important because it shifts attention from treating Rett syndrome only after symptoms appear to understanding the earliest biological triggers, creating possible future opportunities to track disease progression, measure treatment effects and one day intervene before major brain-function loss takes hold.