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

Center for Genetic Disorders of Cognition and Behavior, Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Journal of Intellectual Disability Research (Impact Factor: 2.41). 03/2011; 56(3):233-47. DOI: 10.1111/j.1365-2788.2011.01404.x
Source: PubMed


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.
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.
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).
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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    • "Rett syndrome (RTT) 2 is a severe neurodevelopmental disorder affecting primarily girls, with an incidence of 1:10,000 live births, and represents one of the leading causes of intellectual disability in females [1] [2]. Symptoms are not usually identified until 6–18 months of age, when RTT patients show neurological regression, followed by loss of acquired cognitive, social, communicative, and motor skills [2] [3]. "
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    • "Her strong social interests and interactions were felt to be prohibitive of a diagnosis of autism, despite the fact that she demonstrated other ASD features such as insistence of sameness and repetitive behaviors. This emphasizes the role of MECP2 in mediating core phenotypes of autism(Neul 2012; Kaufmann et al. 2011), and being in accord with previous studies demonstrating ASD traits are often found in girls that ultimately get diagnosed with RTT(Young et al. 2008). "
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    ABSTRACT: Mutations in Methyl-CpG-Binding protein 2 (MECP2) are commonly associated with the neurodevelopmental disorder Rett syndrome (RTT). However, some people with RTT do not have mutations in MECP2, and interestingly there have been people identified with MECP2 mutations that do not have the clinical features of RTT. In this report we present four people with neurodevelopmental abnormalities and clear RTT-disease causing MECP2 mutation but lacking the characteristic clinical features of RTT. One patient's symptoms suggest an extension of the known spectrum of MECP2 associated phenotypes to include global developmental delay with obsessive compulsive disorder and attention deficit hyperactivity disorder. These results reemphasize that RTT should remain a clinical diagnosis, based on the recent consensus criteria.
    Journal of Autism and Developmental Disorders 08/2013; 44(3). DOI:10.1007/s10803-013-1902-z · 3.06 Impact Factor
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    • "In addition, the absence or markedly restricted repertoire and functionality of gestures, a delayed or absent response to interactive stimuli and impairments in joint attention are all antecedents of later developing marked pragmatic difficulties and peculiarities in social reciprocity (Kaufmann et al., 2012; Marschik et al., 2012a). These features, in turn, precede or mirror some autistic symptoms and would seem to refute the assumption that autistic behaviors are a transient or late appearing phenomenon in RTT (Kaufmann et al., 2012). "
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    ABSTRACT: We delineated the achievement of early speech-language milestones in 15 young children with Rett syndrome (MECP2 positive) in the first two years of life using retrospective video analysis. By contrast to the commonly accepted concept that these children are normal in the pre-regression period, we found markedly atypical development of speech-language capacities, suggesting a paradigm shift in the pathogenesis of Rett syndrome and a possible approach to its early detection.
    Research in developmental disabilities 04/2013; 34(4):1236-9. DOI:10.1016/j.ridd.2013.01.014 · 4.41 Impact Factor
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