To investigate the clinical characteristics, genetic features, and follow-up outcomes of children with MECP2 gene mutations.

A retrospective analysis was conducted on the clinical data of 15 children with MECP2 gene mutations diagnosed by molecular testing at the First Affiliated Hospital of Anhui Medical University from October 2017 to March 2025. Data collected included general information, clinical phenotypes, auxiliary examination results, treatment, and follow-up records. Whole-exome sequencing (WES) was performed to detect gene mutations in the children and their parents, with Sanger sequencing for verification and pedigree co-segregation analysis. Pathogenicity grading was performed according to the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines, combined with RTT diagnostic criteria and clinical staging for comprehensive evaluation. This study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Anhui Medical University (Approval No. PJ-2024-12-62), and all legal guardians of the subjects provided written informed consent.

① Among the 15 children, 11 were female and 4 were male. Ten cases met the diagnostic criteria for typical RTT, three were atypical RTT, and two did not meet the RTT diagnostic threshold (one case with pervasive developmental delay and regression, and one with autism spectrum disorder). All typical RTT cases exhibited developmental regression, loss of hand function and language ability, and associated with hand stereotyped movements. Male children showed significant clinical phenotypic heterogeneity. ②At initial diagnosis, six cases had coexisting epilepsy, two had only abnormal electroencephalogram (EEG), and three of the seven with normal EEG developed epilepsy during the course of the disease. At initial diagnosis, 2 cases exhibited abnormal cranial MRI findings. Among the 15 pediatric patients, 5 cases had nonsense mutations, 4 cases had missense mutations, 4 cases had frameshift/splicing site mutations, and 2 cases had copy number variations (CNV). Of these, 12 cases presented with novel mutations, and 3 cases were maternally inherited. According to the ACMG/AMP guidelines, all identified mutations were classified as pathogenic (L) or potentially pathogenic (LP), including a frameshift mutation (p.L383Profs*5) reported for the first time in this study. Among the 13 RTT patients, 10 were in stage Ⅱ at initial diagnosis, and 3 were in stage Ⅰ. Follow-up ranged from 2 to 96 months. Three male patients died, all exhibiting rapid disease progression with severe complications. The disease progression in 9 RTT patients was observed over time, with 1 case showing no progression and 2 cases with stable conditions (non-RTT). Among the 9 cases finally diagnosed with epilepsy, 3 cases were refractory epilepsy with poor prognosis, 4 cases had well-controlled epilepsy, and 2 cases had controlled epilepsy after short-term follow-up.

MECP2 gene mutations are associated with significant clinical phenotypic heterogeneity. Female patients predominantly present with classic RTT phenotypes, while male patients exhibit rapid disease progression and poor prognosis, manifesting as developmental delay or severe fatal encephalopathy. Epilepsy control is correlated with the degree of functional preservation.