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

• Type of Material: Article
• Authors: Daniel Tarquinio, Emory University; Wei Hou, Stony Brook University; Jeffrey L. Neul, Baylor College of Medicine; Walter Kaufmann, Emory University; Daniel G. Glaze, Baylor College of Medicine; Kathleen J. Motil, Baylor College of Medicine; Steven A. Skinner, Greenwood Genetic Center; Hye-Seung Lee, University of South Florida; Alan K. Percy, University of Alabama at Birmingham
• Language: English
• Date: 2015-11-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.pediatrneurol.2015.06.003
• Title of Journal or Parent Work: Pediatric Neurology
• ISSN: 0887-8994
• Volume: 53
• Issue: 5
• Start Page: 402
• End Page: 411
• Grant/Funding Information: 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.
• Keywords: risk factors; Rett syndrome; PREVALENCE; Clinical Neurology; MECP2 MUTATION; mortality; Neurosciences & Neurology; prognosis; HEIGHT; Science & Technology; survival; Life Sciences & Biomedicine; Pediatrics; WEIGHT
• Research Categories: Health Sciences, Medicine and Surgery; Biology, Neuroscience

Abstract

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.