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Clinical and functional outcomes in pediatric patients with Rett syndrome: a 15-year retrospective study
Mariana Cortez Ferreira1, Joana De Beir2, Maria Inês Barreto2,3,4
1Child Developmental Centre, Hospital Pediátrico de Coimbra, Unidade Local de Saúde de Coimbra, Coimbra, Portugal. marianasoferreira@gmail.com.
Insights
Rett syndrome (RTT) patients show neurodevelopmental regression due to MECP2 gene mutations. Early diagnosis and multidisciplinary care, including therapies, are crucial for managing RTT symptoms and improving quality of life.
Area of Science:
- Neurology
- Genetics
- Pediatrics
Background:
- Rett syndrome (RTT) is a rare neurodevelopmental disorder affecting females, characterized by motor and communication skill regression.
- Limited long-term data exist on clinical progression and functional outcomes in pediatric RTT.
Purpose of the Study:
- To characterize RTT patients in Portugal.
- To evaluate clinical patterns, interventions, and outcomes in RTT.
- To analyze epidemiological and clinical data for RTT patients.
Main Methods:
- Retrospective cohort study of RTT patients with pathogenic MECP2 variants.
- Data collected from electronic medical records at a Portuguese tertiary pediatric hospital (2010-2024).
- Review of epidemiological, clinical, and molecular data.
Main Results:
- Twelve RTT patients (91.7% female) were analyzed; median onset at 15 months, diagnosis at 35 months.
- Epilepsy and constipation were common comorbidities; 41.7% were wheelchair-dependent.
- Ten different de novo MECP2 variants were identified; no clear genotype-phenotype correlation found.
Conclusions:
- RTT prevalence remained stable, with a decreased median age at diagnosis.
- Diagnosis relies on clinical features, especially neurodevelopmental regression.
- A multidisciplinary approach with therapies is critical for RTT management.
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.
