Elsevier

The Journal of Pediatrics

Volume 156, Issue 1, January 2010, Pages 135-138.e1
The Journal of Pediatrics

Original Article
Longevity in Rett Syndrome: Analysis of the North American Database

https://doi.org/10.1016/j.jpeds.2009.07.015Get rights and content

Objective

To determine longevity in Rett syndrome (RTT) from a large cohort.

Study design

The North American RTT Database allows the examination of longevity in a large cohort of individuals with RTT from the United States and Canada. This database contains information on 1928 individuals, 85.5% with typical RTT, 13.4% with atypical RTT, and 1.1% with a mutation in the methyl-CpG-binding protein 2 gene (MECP2) but not RTT. Kaplan-Meier analyses were performed to assess longevity.

Results

Earlier decennial cohorts exhibited better survival than recent cohorts, with most participants surviving into middle age. Comparing overall survival in persons with typical RTT and atypical RTT revealed greater mortality in typical RTT across the observed lifespan (P < .0001). Comparing survival in persons with RTT and identified MECP2 mutations and persons with unknown MECP2 status demonstrated greater mortality in the latter group (P < .0001, log-rank test).

Conclusions

This analysis provides strong evidence for significant longevity in RTT and indicates the need for careful planning for long-term care of these women. The disproportionately greater survival seen in earlier time periods and in persons with atypical RTT may be attributed to more severely affected individuals dying before diagnosis in the former and to greater numbers with milder variants (ie, preserved speech and delayed onset) in the latter.

Section snippets

Methods

The IRSA mailed a structured survey to 2994 members in the United States (n = 2836) and Canada (n = 158) requesting specific information, including date of birth, date of death (if applicable), diagnosis (typical RTT, variant or atypical RTT, no RTT, or unknown), discipline of the diagnosing physician, mutation testing results (if performed) and testing laboratory; reason why diagnostic testing was not performed, and contact information (Appendix; available at www.jpeds.com). No response was

Results

The North American RTT Database comprises individuals who fulfill the criteria for typical or variant RTT or who do not meet these criteria but have a MECP2 mutation. The diagnosis of RTT is made by a pediatric neurologist, a developmental pediatrician, a geneticist, or a general pediatrician. Table 1 gives the number of participants and their distribution by diagnosis. This distribution was 85.5% typical RTT, 13.4% atypical RTT, and 1.1% with a MECP2 mutation but not fulfilling the criteria

Discussion

In this analysis, we examined patterns of RTT survival among individuals in North America born before 1960 to the present. From the most recent period to the earliest period, we found a general pattern of better survival with earlier decade of birth. Given that clinical management has improved considerably from the time when RTT was first recognized, improved survival among each successive cohort might be expected.

We speculate that the observed pattern may be linked to the increasing

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Supported by grants from the National Institutes of Health (RR019478) and Mental Retardation Research Center (HD38985), and funds from the International Rett Syndrome Association and Civitan International Research Center. The authors declare no conflicts of interest.

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