Ferreira Mariana Cortez, De Beir Joana, Barreto Maria Inês, Ribeiro Joana Afonso, Pereira Cristina, Oliveira Guiomar
Child Developmental Centre, Hospital Pediátrico de Coimbra, Unidade Local de Saúde de Coimbra, Coimbra, Portugal.
Clinical Academic Center of Coimbra, Hospital Pediátrico de Coimbra, Unidade Local de Saúde de Coimbra, Coimbra, Portugal.
Eur J Pediatr. 2025 Jul 3;184(7):465. doi: 10.1007/s00431-025-06291-6.
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.
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.
• 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.
• 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.
雷特综合征（RTT）是一种由MECP2基因突变引起的神经发育障碍。其特征是早期神经发育明显正常，随后在6至18个月之间出现精神运动发育倒退。目前尚无治愈方法，治疗是多学科的，重点是提高生活质量和功能。本研究旨在对RTT患者进行特征描述，并评估临床模式、干预措施和结局。对2010年至2024年在葡萄牙一家三级儿科医院随访的诊断为RTT且携带致病性MECP2变异的儿童进行了一项回顾性队列研究。查阅了电子病历，并收集了流行病学和临床数据。共随访了12例RTT患者（91.7%为女性）。症状出现的中位年龄为15个月，诊断时的中位年龄为35个月。7例患者（58.3%）患有典型RTT。分子分析鉴定出10种不同的MECP2变异，均为新发突变。癫痫和便秘是最常见的合并症。5例患者（41.7%）依赖轮椅，2例需要无创呼吸支持。几乎所有患者都接受了物理治疗、职业治疗和言语治疗。每位患者慢性药物的中位数量为两种，主要是抗惊厥药。每位患者涉及的医学专科中位数量为两个，神经儿科和神经发育儿科最为常见。
RTT的患病率在20年中保持稳定，诊断时的中位年龄有所下降，这可能是由于认识提高和基因检测增加所致。未发现明确的基因型-表型相关性。RTT的诊断仍然基于临床特征，特别是神经发育倒退。多学科方法至关重要，患者接受了各种治疗和支持。本研究为葡萄牙的RTT提供了有价值的见解，有助于全球知识积累。
• 雷特综合征是一种罕见的神经发育障碍，主要影响女性，其特征是运动和沟通技能倒退。• 关于儿童雷特综合征临床进展和功能结局的长期数据有限。
• 观察到诊断年龄下降，这可能反映了认识提高和基因检测机会增加。• 在有潜在治愈性治疗的临床试验前景广阔的时代，包括葡萄牙在内的大多数国家，个体化的多学科方法仍然是标准治疗。
