Drug-resistant epilepsy and epileptic phenotype-EEG association in MECP2 mutated Rett syndrome.
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.


CONCLUSIONS
These observations could be of help in the practical management and family counseling.
Buoni
Sabrina
S
Pediatrics Neuropsychiatric Unit, Azienda Ospedaliera Universitaria Senese, Policlinico Le Scotte, Siena, Italy.
Zannolli
Raffaella
R
Felice
Claudio De
CD
Saponari
Simona
S
Strambi
Mirella
M
Dotti
Maria Teresa
MT
Castrucci
Elena
E
Corbini
Letizia
L
Orsi
Alessandra
A
Hayek
Joseph
J
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance; D004569:Electroencephalography / Q000379:methods; D004827:Epilepsy / Q000209:etiology* / Q000235:genetics; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D012189:Retrospective Studies; D015518:Rett Syndrome / Q000150:complications* / Q000235:genetics*; D055815:Young Adult
C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2