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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    • "Loss-of-function mutation of one copy of the MECP2 gene is responsible for Rett syndrome and imparts a 50% chance of an autism spectrum diagnosis (Amir et al., 1999; Wulffaert et al., 2009). Social impairments, problems with speech and language, and sensory processing difficulties are common in individuals with Rett syndrome (Kaufmann et al., 2012; Lenn et al., 1986; Urbanowicz et al., 2015). Recent studies have documented that speech and language abilities and the acquisition of early developmental skills are abnormal even in the pre-regression period; while some milestones are reached, acquisition of these skills is often delayed (Marschik et al., 2013; Neul et al., 2014). "
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    ABSTRACT: Individuals with Rett syndrome have greatly impaired speech and language abilities. Auditory brainstem responses to sounds are normal, but cortical responses are highly abnormal. In this study, we used the novel rat Mecp2 knockout model of Rett syndrome to document the neural and behavioral processing of speech sounds. We hypothesized that both speech discrimination ability and the neural response to speech sounds would be impaired in Mecp2 rats. We expected that extensive speech training would improve speech discrimination ability and the cortical response to speech sounds. Our results reveal that speech responses across all four auditory cortex fields of Mecp2 rats were hyperexcitable, responded slower, and were less able to follow rapidly presented sounds. While Mecp2 rats could accurately perform consonant and vowel discrimination tasks in quiet, they were significantly impaired at speech sound discrimination in background noise. Extensive speech training improved discrimination ability. Training shifted cortical responses in both Mecp2 and control rats to favor the onset of speech sounds. While training increased the response to low frequency sounds in control rats, the opposite occurred in Mecp2 rats. Although neural coding and plasticity are abnormal in the rat model of Rett syndrome, extensive therapy appears to be effective. These findings may help to explain some aspects of communication deficits in Rett syndrome and suggest that extensive rehabilitation therapy might prove beneficial. Copyright © 2015. Published by Elsevier Inc.
    Neurobiology of Disease 08/2015; 83. DOI:10.1016/j.nbd.2015.08.019 · 5.08 Impact Factor
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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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