This study examined the relationships among MECP2
mutations, clinical severity, and psychosocial and physical aspects of QOL for individuals with classic RTT. QOL assessment, in general, has received increased attention in recent years with respect to its potential as a useful metric in the conduct of clinical trials. The CHQ-PF50 has been shown to perform effectively in the pediatric age range for both general medical problems11,12
and disorders affecting the central and peripheral nervous systems. The latter include studies on individuals with cerebral palsy13,14
and, more recently, for neurofibromatosis,15
inherited peripheral neuropathies,16
and very low birth weight preterm birth.17
In each neurologic scenario, the CHQ-PF50 was able to detect adverse effects on QOL, suggesting that it could be a useful outcome measure for determining efficacy in clinical trials. This is particularly relevant to RTT as the emergence of credible pharmacologic interventions is widely anticipated.
Therefore, in the present study, both cross-sectional and longitudinal analyses showed that higher scores on the CSS and MBA significantly decreased the CHQ-PF50 physical summary scores. This result suggests that worse clinical status is associated with worse QOL in the physical domain. This finding is not surprising, given that more severe motor impairments most likely impair the ability to carry out motor functions, thereby negatively influencing the physical QOL. However, we also found that higher scores on the CSS were related to better scores on the CHQ-PF50 psychosocial domain, which suggests that participants with worse clinical status tend to have better psychosocial functioning. This finding may seem somewhat counterintuitive. However, it may be that severe clinical impairments (such as very low motor functioning) inhibit those individuals with RTT from being able to engage in negative behaviors such as aggression or self-injury that would otherwise adversely affect their psychosocial QOL. In fact, our in-depth investigation highlighted the fact that worse motor functioning along with earlier age at onset of RTT stereotypies was the area of clinical status that accounted for higher CHQ-PF50 PsS scores. In addition, we did not find any change over time in measurements of clinical severity and QOL during the 2-year course of the study. This may be because developmental change is slow in RTT and may suggest that investigators should lengthen follow-up time for studies.
Family life satisfaction in RTT families has not been reported. A single study from 2006 found that the most important predictors of physical and mental health in mothers of children with Rett syndrome were child behavior, caregiver demands, and family function.20
The CHQ-PF50 assesses Family Cohesion, which is independent of the composite physical and psychosocial scores. Family Cohesion correlates significantly with the PsS score but not with the PhS score. As such, the degree of motor impairment does not seem to affect family cohesion. The CHQ-PF50 does not capture parental stress directly. Rather, it looks at tension, conflict, and the ability of families to get along with one another, which might be perceived as causing stress. It has been suggested that early diagnosis may lead to better services, access to resources, or expectations of outcome. The principal advocacy group, the International Rett Syndrome Foundation, may fill the needs of families with children with recently diagnosed RTT to an extent not available previously, which might decrease family stress for some. We have no evidence to support this idea, however. One feature of RTT that is almost universal and could affect family QOL is sleep dysfunction, which would affect families across the spectrum of involvement.
Our findings may have implications for the applicability of the measures used in this study for individuals with RTT. Overall clinical status scores on both the CSS and the MBA showed significant relationships with the physical QOL score on the CHQ-PF50. This result probably suggests that both clinical status measures and the CHQ-PF50 perform well in this population. However, only the CSS was related to the psychosocial QOL score on the CHQ-PF50, which implies that the CSS, rather than the MBA, more strongly assesses clinical status factors that correlate with the psychosocial components of QOL. Conversely, it may be that the CHQ-PF50, which is a general measure of QOL, does not appropriately measure this construct in the population with RTT, particularly given the surprising finding that worse motor functioning on the CSS was related to better psychosocial QOL. For future research, it may be useful to develop RTT-specific measures of QOL.
The current study has several limitations worth noting. In this study, the CHQ-PF50 questionnaires were completed by parents, not the participants, which may increase the bias in the measurements. However, in that individuals with RTT have significant cognitive and fine motor impairments, the completion of this questionnaire by participants is not feasible. Another limitation of the current study is that statistical analyses were correlational in nature. Thus, we cannot determine whether a causal relation exists between the study variables.
Nevertheless, for children and adolescents with RTT, QOL is significantly related to clinical severity. Whereas poorer physical QOL is related to greater clinical severity, better psychosocial QOL is related to greater motor impairment. Conversely, poorer psychosocial QOL is related to better scores on our measure of clinical severity. As clinical trials in RTT emerge, the CHQ-PF50 may represent one of the important outcome measures.