Rett syndrome (RTT, MIM 312750) is an X-linked neurodevelopmental disorder which occurs in 1. 09/10,000 females. RTT individuals with R168X, R294X, and C-terminal methyl-CpG-binding protein 2 (MECP2) mutations have been observed to be less likely to have seizure onset before 4 years of age. Partial and generalized seizures are reported to occur in RTT. Video-electroencephalogram (EEG) studies have been performed in RTT individuals with a history of seizures. Early onset of seizures is reported to be linked to the combined MECP2 mutations and brain-derived neurotrophic factor (BDNF) polymorphisms. In addition to efficacy in treatment of seizures and potential side effects, antiepileptic drugs (AEDs) may improve non-epileptic behaviors, such as anxiety and breathing dysrhythmia, commonly observed in RTT. A changing epilepsy phenotype has been described in individuals with X-linked cyclin-dependent kinase-like 5 (CDKL5) mutations. The pathogenesis of epilepsy in CDKL5 mutations may be similar to that of MECP2 mutations.