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Brain Dev. 2018 Sep 11. pii: S0387-7604(18)30305-X. doi: 10.1016/j.braindev.2018.08.008. [Epub ahead of print]

Behavioral profiles in Rett syndrome: Data from the natural history study.

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Greenwood Genetic Center, SC, United States.
Baylor College of Medicine, Department of Pediatrics and Neurology, TX, United States.
University of Alabama at Birmingham, Civitan International Research Center, Alabama, AL, United States.
University of Alabama at Birmingham, Department of Pediatrics, Civitan International Research Center, AL, United States.
Vanderbilt Kennedy Center, Vanderbilt University Medical Center, TN, United States.
Greenwood Genetic Center, SC, United States; University of South Carolina School of Medicine, Department of Pediatrics, SC, United States; Emory University School of Medicine, Department of Human Genetics, GA, United States. Electronic address:



Rett syndrome (RTT) is a complex neurodevelopmental disorder with known behavioral abnormalities, both internalizing (e.g., anxiety, social withdrawal) and externalizing (e.g., aggression, self-abuse). However, a broad evaluation of behavioral abnormalities in a large cohort is lacking.


In this report, we describe profiles of internalizing and externalizing behaviors in individuals evaluated in the multi-center U.S. Rett Natural History Study.


Cross-sectional and longitudinal data were collected from 861 females with RTT and from 48 females who have MECP2 mutations without meeting criteria for RTT. Standard statistical methods including linear regression evaluated internalizing behavioral components from the Child Health Questionnaire (CHQ-PF50) and externalizing components from the Motor Behavioral Assessment (MBA).


We found mildly to moderately severe internalizing behaviors in nearly all individuals with RTT, while externalizing behaviors were mild and uncommon. Internalizing behavior in RTT was comparable to groups with psychiatric disorders. Participants with mixed (internalizing and externalizing) behaviors were younger and less affected overall, but showed prominent self-injury and worsening internalizing behaviors over time.


This study revealed that internalizing behaviors are common at a clinically significant level in RTT. Understanding clinical features associated with behavioral profiles could guide treatment strategies.


Behavior and behavior mechanisms; Observational study; Problem behavior; Rett syndrome

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