Abstract
Rett syndrome (RTT) is a neurological disorder caused by mutations in the MECP2 gene. It is characterized by apparently normal early neurodevelopment followed by psychomotor regression between 6 and 18 months. There is no cure, and treatment is multidisciplinary, focusing on improving quality of life and functionality. This study aims to characterize RTT patients and evaluate clinical patterns, interventions, and outcomes. A retrospective cohort study was conducted of children diagnosed with RTT and a pathogenic MECP2 variant, followed at a Portuguese tertiary pediatric hospital from 2010 to 2024. Electronic medical records were reviewed, and epidemiological and clinical data were collected. Twelve RTT patients were followed (91.7% female). The median age at symptom onset was 15 months, and at diagnosis, 35 months. Seven patients (58.3%) had classic RTT. Molecular analysis identified 10 different MECP2 variants, all de novo mutations. Epilepsy and constipation were the most common comorbidities. Five patients (41.7%) were wheelchair-dependent, and two required non-invasive respiratory support. Almost all patients received physical, occupational, and speech therapies. The median number of chronic medications per patient was two, primarily anticonvulsants. The median number of medical specialties per patient was two, with neuropediatrics and neurodevelopmental pediatrics being the most frequent. CONCLUSIONS: RTT prevalence remained stable over 20 years, with a decreased median age at diagnosis, likely due to increased awareness and genetic testing. No clear genotype-phenotype correlation was found. RTT diagnosis remains based on clinical features, particularly neurodevelopmental regression. A multidisciplinary approach was critical, with patients receiving various therapies and support. This study provides valuable insights into RTT in Portugal, contributing to global knowledge. WHAT IS KNOWN: • Rett syndrome is a rare neurodevelopmental disorder primarily affecting females, characterized by regression of motor and communication skills. • Limited long-term data exist on clinical progression and functional outcomes in pediatric Rett syndrome. WHAT IS NEW: • A decreasing age at diagnosis was observed, likely reflecting increased awareness and access to genetic testing. • In an era of promising clinical trials for potential curative treatments, an individualized, multidisciplinary approach remains the standard of care in most countries, including Portugal.