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. 2010 Mar 16;74(11):909-12.
doi: 10.1212/WNL.0b013e3181d6b852.

Epilepsy and the natural history of Rett syndrome

D G Glaze  1 , A K Percy, S Skinner, K J Motil, J L Neul, J O Barrish, J B Lane, S P Geerts, F Annese, J Graham, L McNair, H-S Lee
Affiliations

Epilepsy and the natural history of Rett syndrome

D G Glaze et al. Neurology. .

Abstract

Background: Rett syndrome (RTT) is a neurodevelopmental disorder primarily seen in females, most with a mutation in MECP2. Epilepsy has been reported in 50%-80%. Previous reports were based on small sample sizes or parent-completed questionnaires, or failed to consider the impact of specific MECP2 mutations.

Methods: The Rare Disease Consortium Research Network for RTT is an NIH-funded project to characterize the clinical spectrum and natural history of RTT in advance of clinical trials. Evaluations include clinical status (classic vs atypical RTT), MECP2 mutations, clinical severity, and presence, frequency, and treatment of seizures.

Results: Enrollment as of June 2008 is 602; 528 (88%) meet clinical criteria for classic RTT. Of these, 493 (93%) have MECP2 mutations. Age range was 8 months to 64 years. A total of 360 (60%) were reported to have seizures, including 315 (60%) classic and 45 (61%) atypical RTT. Physician assessment of the 602 indicated that 48% had seizures. There was no significant difference in seizure occurrence by race/ethnicity. A significant age impact for seizures was seen and seizures were infrequent before age 2 years. MECP2 mutations most frequently associated with epilepsy were T158M (74%) and R106W (78%), and less frequently R255X and R306C (both 49%). Individuals with seizures had greater overall clinical severity, and greater impairment of ambulation, hand use, and communication.

Discussion: Seizures are common in Rett syndrome, have an age-related onset and occurrence, vary by mutation, and are associated with greater clinical severity. This information represents a key consideration for designing clinical trials.

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Figures

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Figure 1 Occurrence of epilepsy at first visit
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Figure 2 Frequency of epilepsy in Rett syndrome by age
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Figure 3 Frequency of epilepsy in Rett syndrome by mutation type
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References

    1. Hagberg B, Hanefield F, Percy A, Skjeldel O. An update on clinically applicable diagnostic criteria in Rett syndrome. Eur J Pediatr Neurol 2002;6:293–297. - PubMed
    1. Neul J, Fang J, Barrish J, et al. Specific mutations in methyl-CpG-binding protein 2 confer different severity in Rett syndrome. Neurology 2008;70:1311–1321. - PMC - PubMed
    1. Fitzgerald PM, Jankovic J, Glaze DG, Schultz RJ, Percy AK. Extrapyramidal involvement in Rett syndrome. Neurology 1990;40:293–295. - PubMed
    1. Nadia BB, Isabelle G, Rima N, et al. Parental view of epilepsy in Rett syndrome. Brain Dev 2008;30:126–130. - PubMed
    1. Jian L, Nagarajan L, de Klerk N, Ravine D, Christodoulou J, Leonard H. Seizures in Rett syndrome: an overview from a one-year calendar study. Eur J Paediatr Neurol 2007;11:310–317. - PMC - PubMed

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