About this item:

432 Views | 247 Downloads

Author Notes:

Address correspondence to Alan K. Percy, 1720 2nd Avenue South, CIRC 320E, Birmingham, AL 35294-0021, Telephone: 205-996-4927, Facsimile: 205-975-6330.

The authors thank Eric Pedrotty for statistical analysis of socioeconomic data. The authors acknowledge the gracious participation and provision of information by the families of the reported participants. Dr. Mary Lou Oster-Granite, Health Scientist Administrator at NICHD, provided invaluable guidance, support, and encouragement for this Rare Disease initiative.

The authors report no conflicts of interest.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.


Research Funding:

The Angelman, Rett, Prader-Willi syndrome consortium (U54HD61222) is part of the Rare Diseases Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research (ORDR), National Center for Advancing Translational Science (NCATS). This consortium is funded through collaboration between NCATS, and the Eunice Kennedy Shriver Child Health and Human Development Institute.

This research was also supported by the International Rett Syndrome Foundation, the Civitan International Research Center, and NIH RR019478.


  • Science & Technology
  • Life Sciences & Biomedicine
  • Clinical Neurology
  • Pediatrics
  • Neurosciences & Neurology
  • Rett syndrome
  • risk factors
  • prognosis
  • survival
  • mortality

The Changing Face of Survival in Rett Syndrome and MECP2-Related Disorders


Journal Title:

Pediatric Neurology


Volume 53, Number 5


, Pages 402-411

Type of Work:

Article | Post-print: After Peer Review


Purpose: Survival in Rett syndrome (RTT) remains unclear. Although early estimates were grim, more recent data suggest that survival into adulthood is typical. We aimed to define survival in RTT more clearly and identify risk factors for early death. Methods: Participants with clinical RTT or Methyl CpG Binding Protein 2 mutations without clinical RTT were recruited through the RTT Natural History study from 2006 to 2015. Clinical details were collected, and survival was determined using the Kaplan-Meier estimator. Risk factors were assessed using Cox proportional hazards models. Results: Among 1189 valid participants, 51 died (range 3.9–66.6 years) during the 9-year follow-up period. Those who died included 36 (3.9%) classic RTT females, 5 (5.9%) atypical severe RTT females, 1 (2.4%) non-RTT female, the single atypical severe male, 6 (30%) non-RTT males, and 2 (7.1%) DUP males. All atypical mild RTT females, DUP females and the single classic RTT male remain alive. Most deaths were due to cardiorespiratory issues. Only one died due to severe malnutrition, scoliosis, and extreme frailty. Survival for classic and atypical RTT was greater than 70% at 45 years. Overall severity and several modifiable risk factors, including ambulation, weight, and seizures, were associated with mortality in classic RTT. Conclusions: Survival in to the 5th decade is typical in RTT, and death due to extreme frailty has become rare. While the leading cause of death remains cardiorespiratory compromise, many risk factors for early death are modifiable. Intense therapeutic approaches could further improve the prognosis for patients with RTT.

Copyright information:

© 2015 Elsevier Inc.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Creative Commons License

Export to EndNote