The Changing Face of Survival in Rett Syndrome and MECP2-Related Disorders.
OBJECTIVE
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.
Department of Pediatrics, Emory University, Atlanta, Georgia.
Daniel C
DC
Tarquinio
Stony Brook University Medical Center, Stony Brook, New York.
Wei
W
Hou
Department of Pediatrics, Duncan Neurological Research Institute, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas.
Jeffrey L
JL
Neul
Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
Walter E
WE
Kaufmann
Department of Pediatrics, Duncan Neurological Research Institute, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas.
Daniel G
DG
Glaze
Department of Pediatrics, Duncan Neurological Research Institute, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas.
Kathleen J
KJ
Motil
Greenwood Genetic Center, Greenwood, South Carolina.
Steven A
SA
Skinner
Pediatrics Epidemiology Center, University of South Florida, Tampa, Florida.
Hye-Seung
HS
Lee
Civitan International Research Center, University of Alabama at Birmingham, Alabama. Electronic address: apercy@uab.edu.
Alan K
AK
Percy
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D008875:Middle Aged; D016016:Proportional Hazards Models; D015518:Rett Syndrome / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D012307:Risk Factors; D014481:United States; D055815:Young Adult
C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2
Rett syndrome; mortality; prognosis; risk factors; survival