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Published on: September 20, 2024
Drug-resistant epilepsy and epileptic phenotype-EEG association in MECP2 mutated Rett syndrome
Sabrina Buoni1, Raffaella Zannolli, Claudio De Felice
1Pediatrics Neuropsychiatric Unit, Azienda Ospedaliera Universitaria Senese, Policlinico Le Scotte, Siena, Italy.
Objective:
To determine in MECP2-mutated Rett syndrome (RTT [MIM 312750]): (1) the prevalence of drug-resistant epilepsy (DRE); (2) whether the presence of DRE is related to the abnormal EEG patterns or to the particular MECP2 mutant genotype.
Methods:
Retrospective survey of a large population of patients (n=154) evaluated between 1978 to 2007 (May) at the Child Psychiatry and Neurology Unit of Siena (Italy) with both clinical and genetic (i.e. MECP2 mutated) diagnoses of RTT. Some subjects were followed for up to 20 years. Among those, cases with epilepsy were first selected for study; within that group, cases with DRE were identified and studied. The association between clinical severity of their epilepsy and quantitative or qualitative scores of EEG severity was tested using rank coefficients (Spearman's rho values). The relationship between DRE and RTT genotype category (i.e. gene deletion, gene duplication, early truncating mutation, late truncating mutation, and missense mutation) or a specific MECP2 genotype was tested using the chi-square test. A p-value <0.05 (two sided) was considered to indicate statistical significance.
Results:
Prevalence of DRE was 16% (i.e. 16 DRE out of 100 MECP2-mutated RTT epileptic patients). No significant relationship was found between clinical severity of DRE and quantitative (p=0.9190) or qualitative EEG scores (p=0.1511). In addition, no significant relationship was found between the DRE and the RTT genotype category (chi-square=1.147, DF=4, p=0.8867), or a specific MECP2 genotype (chi-square=30.958, DF=39, p=0.8173).
Conclusions:
Although RTT MECP2-mutated patients suffer from a serious and progressive encephalopathy, it is "epileptogenic" but not "DREgenic" as they have a decreased risk (16%) for DRE compared to the general epileptic population (DRE: 20-40%). The presence of DRE is not related to abnormal EEG findings or a particular MECP2 mutant genotype.
Significance:
These observations could be of help in the practical management and family counseling.
Insights
Drug-resistant epilepsy (DRE) is less common in MECP2-mutated Rett syndrome (RTT) patients than in the general epileptic population. DRE occurrence in RTT is not linked to specific EEG patterns or MECP2 gene mutations.
Area of Science:
- Neurology
- Genetics
- Epileptology
Background:
- Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by mutations in the MECP2 gene.
- Epilepsy is a common comorbidity in RTT, significantly impacting patient prognosis and quality of life.
- Drug-resistant epilepsy (DRE) presents a therapeutic challenge, necessitating a deeper understanding of its prevalence and associated factors in specific patient populations.
Purpose of the Study:
- To investigate the prevalence of DRE in patients with MECP2-mutated RTT.
- To determine if DRE in RTT is associated with specific electroencephalogram (EEG) abnormalities.
- To explore the relationship between DRE and distinct MECP2 mutation genotypes in RTT.
Main Methods:
- A retrospective analysis was conducted on 154 patients diagnosed with MECP2-mutated RTT.
- Patients with epilepsy were identified, and within this group, those with DRE were specifically studied.
- Statistical analyses, including Spearman's rho and chi-square tests, were employed to assess associations between DRE, EEG findings, and MECP2 genotypes.
Main Results:
- The prevalence of DRE was found to be 16% among MECP2-mutated RTT patients with epilepsy.
- No significant correlation was observed between the clinical severity of DRE and quantitative or qualitative EEG scores.
- The study found no significant relationship between DRE and the category of RTT genotype or specific MECP2 mutations.
Conclusions:
- MECP2-mutated RTT is associated with a lower risk of DRE (16%) compared to the general epileptic population (20-40%).
- The presence of DRE in RTT is not influenced by abnormal EEG findings or specific MECP2 genotypes.
- These findings can aid in the clinical management and family counseling for individuals with RTT and epilepsy.
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