Rett syndrome is a severe and progressive developmental encephalopathy of genetic origin caused by a mutation in the MECP2 gene, a gene involved in synaptic functioning and dendritic integration of neuronal structures. It is an X-linked condition, so the disease is primarily present in women. Rett syndrome constitutes one of the most common genetic causes of severe intellectual disability in the world with a prevalence of more than 350,000 patients, corresponding to 1 in 10 girls in 20,000. Patients have normal early development , followed by psychomotor regression which occurs between the ages of 6 and 18 months. This disease is currently incurable. However, various phase II and III clinical trials of neuroprotective agents and phase I/II gene therapy trials aimed at restoring MECP2 expression are ongoing worldwide. CHU Sainte-Justine was elected to initiate the first gene therapy trial in adult patients with Rett Syndrome (REVEAL study, Taysha). A pediatric phase is to come in case of good tolerance in adults. The evaluation of these clinical trials is mainly based on clinical scores: behavior, motor skills, communication, convulsions, breathing habits and sleep. Electrophysiological measurements will provide better characterization of potential biomarkers linked to the progression of the disease, thus allowing an in-depth understanding of therapeutic responses in patients. Furthermore, these measurements will contribute to deepening our knowledge of the biology of neuronal network dysfunction associated with Rett syndrome.
