J Pediatr. 2006 Mar;148(3):347-52
Rett syndrome in Australia: a review of the epidemiology
Laurvick CL, de Klerk N, Bower C, Christodoulou J, Ravine D, Ellaway C, Williamson S, Leonard H.
Telethon Institute for Child Health Research, Centre for Child Health Research, The University of Western Australia, Perth
Abstract
OBJECTIVE: To examine the prevalence, cumulative incidence, and survival in an Australian cohort with Rett syndrome (RTT). STUDY DESIGN: The Australian Rett Syndrome Database is a longitudinal data collection that included 276 verified female cases at the end of 2004. Survival was calculated using the Kaplan-Meier product limit method, and cumulative incidence was determined using the complement of the Kaplan-Meier method. RESULTS: Most cases (88.4%) have had MECP2 mutation testing, with positive results in 73%. The prevalence of RTT was .88 per 10,000 females in 5- to 18-year-olds, and the cumulative incidence was 1.09 per 10,000 females by 12 years of age. The cumulative incidence by the age of 5 years increased from .39 per 10,000 in the 1980 to 1984 cohort to .76 per 10,000 in birth cohorts beyond 1984. Survival was 77.8% at 25 years, compared with 99.96% survival in the Australian female population. Pneumonia (10/25) was the most common cause of death. CONCLUSIONS: The availability of genetic testing has contributed to the changing pattern and timing of RTT diagnosis in Australia. Girls with RTT have worse survival compared with the general female population. When more data are available, it will be possible to evaluate the relationship between survival and specific MECP2 mutations.Lay Summary
As improved MECP2 genetic diagnostic testing develops, and increased awareness of Rett syndrome occurs, it is possible that the pattern and timing of diagnosis of Rett syndrome is changing. Thus, in this article, the authors re-examine the prevalence and incidence of Rett syndrome in Australia. Overall, the prevalence of Rett syndrome was 1 in 11,400 females in 5- to 18-year-olds, which is similar to the known worldwide incidence. By end of 1994, 276 verified female and 2 male cases were born since 1976, where the average age at diagnosis was 5.3 years. Of this entire group, twenty-five (9.1%) have died from a variety of causes. The most common cause of death was pneumonia (10 patients) followed by respiratory failure (4) and aspiration/asphyxiation (3). Interestingly, there was no difference in survival between classical and atypical cases. Probably the most interesting finding in this investigation was that the prevalence of Rett syndrome among 5- to 18-year-olds described here was significantly higher than that found a similar study performed in 1997. The authors suggest a number of reasons for this apparent increase: 1) increased availability of DNA testing; 2) earlier and improved diagnoses because pediatricians and neurologists have a better awareness of Rett syndrome; 3) improved clinical management is leading to improved outcomes, and less mortality, and thus appearing as a greater incidence of Rett syndrome. Indeed, these types of studies are important, as when more data are available, it will be theoretically possible to evaluate the relationship between survival, symptoms, and specific MECP2 mutations.