Abstract
Purpose
Survival in Rett syndrome remains unclear. Although early estimates were grim, more
recent data suggest that survival into adulthood is typical. We aimed to define survival
in Rett syndrome more clearly and identify risk factors for early death.
Methods
Participants with clinical Rett Syndrome or methyl-CpG-binding protein 2 mutations without clinical RTT were recruited through the Rett Syndrome 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 Rett syndrome females, 5 (5.9%)
atypical severe Rett syndrome females, 1 (2.4%) non-Rett syndrome female, the single
atypical severe male, 6 (30%) non-Rett syndrome males, and 2 (7.1%) methyl-CpG-binding protein 2 duplication syndrome males. All atypical mild Rett syndrome females, methyl-CpG-binding protein 2 duplication syndrome females, and the single classic Rett syndrome male remain alive.
Most deaths were due to cardiorespiratory issues. Only one died from severe malnutrition,
scoliosis, and extreme frailty. Survival for classic and atypical Rett syndrome 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
Rett syndrome.
Conclusions
Survival into the fifth decade is typical in Rett syndrome, and death due to extreme
frailty has become rare. Although the leading cause of death remains cardiorespiratory
compromise, many risk factors for early death are modifiable. Intense therapeutic
interventions could further improve the prognosis for individuals with Rett syndrome.
Keywords
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Article info
Publication history
Published online: June 25, 2015
Accepted:
June 5,
2015
Received:
May 22,
2015
Identification
Copyright
© 2015 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
