Original article
Rett syndrome in Australia: A review of the epidemiology

https://doi.org/10.1016/j.jpeds.2005.10.037Get rights and content

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.

Section snippets

Methods

The ARSD was established in 1993 as a population-based registry.25 Cases are identified from multiple sources, including the Australian Paediatric Surveillance Unit 26 and the Rett Syndrome Association of Australia, a parent support group. Upon enrollment, questionnaires are administered to the child’s clinician and family. Information from these questionnaires is used to verify case status. Verification currently requires either the presence of a pathogenic MECP2 mutation or the presence of at

Results

By Dec 31, 2004, 276 verified female and 2 male cases born since 1976 had been registered with the study. For the purposes of this analysis, the two males were excluded. The revised criteria for classical RTT were met by 67% of the verified cases and 74% of the mutation-positive cases (Table II). Ninety-five percent (264/276) of cases were born in Australia. The mean age at diagnosis was 5.3 years (SD 3.9). Cases were proportionally distributed by state and territory, as for the general

Discussion

In the ARSD, genetic information has been helpful in providing verification in those cases where clinical data may be incomplete and thus the clinical criteria are not fully satisfied. Genetic testing is particularly valuable to clinicians in those subjects who are younger than 5 years old and who may not yet have developed a full “Rett phenotype.” It is likely that the availability of genetic testing could have changed the pattern of diagnosis elsewhere, as it has done in Australia. We found

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  • Cited by (0)

    Supported by the National Institute of Child Health and Human Development under National Institutes of Health grant 1 R01 HD43100-01A1. Helen Leonard is funded by NHMRC program grant 353514, Dr Carol Bower by NHMRC fellowship 353628, and Dr John Christodoulo by NHMRC project grants 185202 and 346603.

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