Clinical severity and quality of life in children and adolescents with Rett syndrome.

OBJECTIVE: The clinical features and genetics of Rett syndrome (RTT) have been well studied, but examination of quality of life (QOL) is limited. This study describes the impact of clinical severity on QOL among female children and adolescents with classic RTT. METHODS: Cross-sectional and longitudinal analyses were conducted on data collected from an NIH-sponsored RTT natural history study. More than 200 participants from 5 to 18 years of age with classic RTT finished their 2-year follow-up at the time of analysis. Regression models after adjustment for their MECP2 mutation type and age at enrollment were used to examine the association between clinical status and QOL. RESULTS: Severe clinical impairment was highly associated with poor physical QOL, but worse motor function and earlier age at onset of RTT stereotypies were associated with better psychosocial QOL; conversely, better motor function was associated with poorer psychosocial QOL. CONCLUSIONS: Standard psychosocial QOL assessment for children and adolescents with RTT differs significantly with regard to their motor function severity. As clinical trials in RTT emerge, the Child Health Questionnaire 50 may represent one of the important outcome measures.

Epilepsy and the natural history of Rett syndrome.

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.