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

Abstract

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. Rett syndrome (RTT), a neurodevelopmental disorder occurring in 1 of 10,000 female births, 1-5 is characterized by apparently normal psychomotor development during the first 6 -18 months of life followed by regression (loss of purposeful hand use and spoken communication skills), social withdrawal, cognitive impairment, gait dysfunction, 6 and stereotypic hand movements, a hallmark of RTT. 7 Mutations in the methyl-CpG-binding protein 2 gene (MECP2), located at Xq28, account for approximately 95% of individuals with RTT. 8,9 Among the more than 250 different pathogenic mutations, the 8 most common point mutations account for about 60% of individuals with RTT. Small deletions in the C-terminal region of MeCP2 represent an additional 7%-9% and large-scale deletions represent 8%-10%. 10The spectrum of clinical severity for individuals with RTT correlates with specific mutations. Little is known about the impact of RTT on quality of life (QOL). In anticipation of clinical trials, it is essential to understand the applicability of a general QOL measure, particu-

Evaluation of Current Pharmacological Treatment Options in the Management of Rett Syndrome: From the Present to Future Therapeutic Alternatives.

“…Continued clinical research is required to limit the severity of RTT, but also to continue to increase the quality of life for RTT patients and their families. 144 In addition, we have brought attention, summarized in the Table, to the pre-clinical development of novel pharmacological agents that have been effective in ameliorating symptoms in mouse and cell culture models of RTT. We focused on three potential treatment strategies, but several other alternatives exist.…”

Neurobiologically-based treatments in Rett syndrome: opportunities and challenges

“…In neurodevelopmental disorders, functioning is typically captured by adaptive behavior scales [27] or instruments measuring activities of daily living [132], both providing a more direct view of the actual capacity and level of independence of the patients. QoL has been studied at the level of individuals with RTT [133] and their caretakers [134] using the Child Health Questionnaire 50 and the Optum SF-36v2 Health Survey, respectively. Interestingly, while in children and adolescents with RTT clinical severity was directly correlated with poor physical QoL, motor function was inversely correlated with psychosocial QoL.…”

Conceptualizing a quality of life framework for girls with Rett syndrome using qualitative methods

“…The generic Child Health Questionnaire (CHQ) [Waters et al, 2000] has been used to measure QOL of children with Rett syndrome [Lane et al, 2011]. Children with more severe impairments had poorer physical QOL scores but better psychosocial QOL scores, possibly because these children were less likely to exhibit challenging behaviors [Lane et al, 2011]. These data provide us with the first leads on QOL in children with Rett syndrome.…”

“…Interviews with parents of children with autism spectrum disorder [Tavernor et al, 2013] and cerebral palsy [Young et al, 2007] have suggested that generic child QOL measures are unlikely to account for the condition-specific characteristics and needs of children with disabilities. The generic Child Health Questionnaire (CHQ) [Waters et al, 2000] has been used to measure QOL of children with Rett syndrome [Lane et al, 2011]. Children with more severe impairments had poorer physical QOL scores but better psychosocial QOL scores, possibly because these children were less likely to exhibit challenging behaviors [Lane et al, 2011].…”