Purpose: Rett syndrome (RTT), an X-linked, dominant neurodevelopmental disorder caused by mutations in the methyl-CpG-binding protein 2 (MECP2) gene, presents with acquired microcephaly, autistic regression, hand usage loss, and stereotypies. Epilepsy is frequent and has been reported to correlate with mutation type, general disease severity, and BDNF polymorphism. Our purpose was a comprehensive description of epilepsy features and course in RTT.
Methods: Retrospective review of charts and electroencephalography (EEG) studies in 97 patients with RTT.
Results: Seventy-two percent of patients had epilepsy, appearing at a median age of 3 years. According to age of onset, we divided patients into three groups: 6 with early epileptic variant (0-1 year), 42 with early epilepsy (1-5 years), and 20 with late epilepsy (after 5 years). Early epileptic variant had severe seizure types in the first year of life, followed by a typical RTT picture; all were MECP2 negative. Early epilepsy and late epilepsy groups were similar with respect to Rett-related symptoms, but seizures were better controlled in the second group (p < 0.05). Epileptiform activity appeared earlier and was more confluent in the early epilepsy group, including nine patients with electrical status epilepticus during sleep (ESES) versus one in the late epilepsy group (p < 0.05). No correlation was found between epilepsy onset or severity and genotype. BDNF val/met polymorphism correlated with earlier onset of seizures (p < 0.05).
Discussion: Epilepsy appears earlier than described previously, frequently during the regression stage. Early age of onset predicts a more severe course of seizures. ESES is common among those with early onset epilepsy. BDNF polymorphism was the only genetic correlate with seizure onset, whereas MECP2 mutation type and location did not influence epilepsy.