Social impairments in Rett syndrome: characteristics and relationship with clinical severity

Authors

  • W. E. Kaufmann,

    Corresponding author
    1. Center for Genetic Disorders of Cognition and Behavior, Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    2. Department of Psychiatry, Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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    • These authors made equivalent contributions to this paper.

  • E. Tierney,

    1. Center for Genetic Disorders of Cognition and Behavior, Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    2. Department of Psychiatry, Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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    • These authors made equivalent contributions to this paper.

  • C. A. Rohde,

    1. Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
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  • M. C. Suarez-Pedraza,

    1. Center for Genetic Disorders of Cognition and Behavior, Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    2. Department of Psychiatry, Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • M. A. Clarke,

    1. Center for Genetic Disorders of Cognition and Behavior, Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    2. Department of Psychiatry, Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • C. F. Salorio,

    1. Department of Neuropsychology, Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • G. Bibat,

    1. Department of Neurogenetics, Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • I. Bukelis,

    1. Center for Genetic Disorders of Cognition and Behavior, Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    2. Department of Psychiatry, Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • D. Naram,

    1. Center for Genetic Disorders of Cognition and Behavior, Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    2. Department of Psychiatry, Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • D. C. Lanham,

    1. Center for Genetic Disorders of Cognition and Behavior, Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    2. Department of Psychiatry, Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • S. Naidu

    1. Department of Neurogenetics, Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • This research was supported by NIH grants HD 24448 and HD 24061 and by Institute for Clinical and Translational Research award UL1 RR025005.

Professor Walter E. Kaufmann, Center for Genetic Disorders of Cognition & Behavior, Kennedy Krieger Institute, Baltimore, MD 21205, USA (e-mail: kaufmann@kennedykrieger.org).

Abstract

Background  While behavioural abnormalities are fundamental features of Rett syndrome (RTT), few studies have examined the RTT behavioural phenotype. Most of these reports have focused on autistic features, linked to the early regressive phase of the disorder, and few studies have applied standardised behavioural measures. We used a battery of standardised measures of behaviour and functioning to test the following hypotheses: (1) autistic behaviour is prominent throughout childhood in RTT; (2) autistic features are more salient in individuals with milder presentation; (3) severity of autistic behaviour is associated with a wider range of behavioural problems; and (4) specific MECP2 mutations are linked to more severe autistic behaviour.

Methods  Eighty MECP2 mutation-positive girls with RTT (aged 1.6–14.9 years) were administered: (1) the Screen for Social Interaction (SSI), a measure of autistic behaviour suited for individuals with severe communication and motor impairment; (2) the Rett Syndrome Behaviour Questionnaire (RSBQ), covering a wide range of abnormal behaviours in RTT; (3) the Vineland Adaptive Behavior Scales (VABS); and (4) a modified version of the Rett Syndrome Severity Scale (RSSS). Regression analyses examined the predictive value of age and RSSS on autistic behaviour and other behavioural abnormalities. T-tests further characterised the behavioural phenotype of individual MECP2 mutations.

Results  While age had no significant effect on SSI or RSBQ total scores in RTT, VABS Socialization and Composite scores decreased over time. Clinical severity (i.e. RSSS) also increased with age. Surprisingly, SSI performance was not related to either RSSS or VABS Composite scores. Autistic behaviour was weakly linked with the RSBQ Hand behaviour factor scores, but not with the RSBQ Fear/Anxiety factor. Clinical (neurological) severity did not predict RSBQ scores, as evidenced by the analysis of individual MECP2 mutations (e.g. p.R106W, p.R270X and p.R294X).

Conclusions  Our data suggest that in RTT, autistic behaviour persists after the period of regression. It also demonstrated that neurological and behavioural impairments, including autistic features, are relatively independent of one another. Consistent with previous reports of the RTT phenotype, individual MECP2 mutations demonstrate complex associations with autistic features. Evidence of persistent autistic behaviour throughout childhood, and of a link between hand function and social skills, has important implications not only for research on the RTT behavioural phenotype, but also for the clinical management of the disorder.

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