The spectrum of the behavioral phenotype in boys and adolescents 47,XXY (Klinefelter syndrome)

University of Colorado School of Medicine, Department of Pediatrics, and Child Development Unit, The Children's Hospital, Aurora, CO 80045, USA.
Pediatric endocrinology reviews: PER 12/2010; 8 Suppl 1:151-9.
Source: PubMed


The behavioral phenotype of 47,XXY (Klinefelter syndrome) includes increased risks for developmental delays, language-based learning disabilities, executive dysfunction/ADHD, and socialemotional difficulties. However there is significant variability between individuals with 47,XXY, and many children and adolescents have minimal or no behavioral features while others have quite significant involvement. This paper describes behavioral features in a cohort of 57 children and adolescents with 47,XXY, including results on standardized measures of behavior (BASC-2), attention (Conner's Rating Scales), and social skills (Social Responsiveness Scale). A subset was directly assessed for autism spectrum disorders using the ADOS and ADIR. We discuss our results within the context of previous literature, including implications for genetic counseling, recommendations for care, and areas for future research.

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Available from: Lisa Cordeiro, Sep 29, 2015
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    • "Behavioral features are not homogeneous, including attention disorders, impaired social skills, autism spectrum symptoms, and other psychiatric disturbance [9]. There is also a strong variability among affected individuals , from minimal to significant cognitive and behavioral disorders [10]. When patients with KS have a normal IQ, the attention deficit could be a strong indicator of a genotype that may be otherwise unrecognized. "
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    ABSTRACT: This paper describes a 17-year-old boy who was diagnosed with Klinefelter syndrome (KS) (XXY) at the age of 16 years. Although cognitive level was absolutely normal, he showed attentional difficulties that negatively affected school adjustment. He was successfully treated with methylphenidate. A significant improvement was observed in the ADHD Rating Scale IV and in the inattention subscale score of the Conners Scales. The CGI-S score improved from 3 to 1, and the CGI-I score at the end point was 1 (very much improved). Also attention measures, particularly forward and backward digit span, improved with MPH treatment. Given the widely variable and often aspecific features, KS may run undiagnosed in a large majority of affected patients. A close attention to the cognitive phenotype may favour a correct diagnosis, and a timely treatment.
    08/2014; 2014:980401. DOI:10.1155/2014/980401
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    • "Individuals with an atypical karyotype concerning the sex chromosomes have often been reported to have increased chances of developing autism, or autism-like symptoms. Males with the Klinefelter syndrome (47,XXY) show socio-emotional difficulties (Geschwind and Boone, 2000; Tartaglia et al., 2010) and show increased levels of autistic and schizotypical traits and are often diagnosed with ASD (Bishop et al., 2011; van Rijn and Swaab, 2011). Also 47,XYY males and 48,XXYY males seem to have an increased rate of autism and 47,XXX females show an increased level of mild communication difficulties (Bishop et al., 2011; Bruining et al., 2009; Geerts et al., 2003; Tartaglia et al., 2008). "
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    ABSTRACT: The male predominance of autism spectrum disorders (ASD) is one of the best-known, and at the same time, one of the least understood characteristics of these disorders. In this paper we review genetic, epigenetic, hormonal, and environmental mechanisms underlying this male preponderance. Sex-specific effects of Y-linked genes (including SRY expression leading to testicular development), balanced and skewed X-inactivation, genes that escape X-inactivation, parent-of-origin allelic imprinting, and the hypothetical heterochromatin sink are reviewed. These mechanisms likely contribute to etiology, instead of being simply causative to ASD. Environments, both internal and external, also play important roles in ASD's etiology. Early exposure to androgenic hormones and early maternal immune activation comprise environmental factors affecting sex-specific susceptibility to ASD. The gene-environment interactions underlying ASD, suggested here, implicate early prenatal stress as being especially detrimental to boys with a vulnerable genotype.
    Frontiers in Neuroendocrinology 04/2014; 35(3). DOI:10.1016/j.yfrne.2014.03.006 · 7.04 Impact Factor
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    • "These social difficulties include shyness, social withdrawal, social anxiety, difficulties in peer-relationships, social impulsivity, communication difficulties, depressed adaptive skills, and reduced social assertiveness [9]–[16]. Also, recent studies have suggested that boys and men with Klinefelter syndrome are at increased risk for autism traits and symptoms [13], [17]–[20]. "
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    ABSTRACT: Individuals with an extra X chromosome (Klinefelter syndrome) are at risk for problems in social functioning and have an increased vulnerability for autism traits. In the search for underlying mechanisms driving this increased risk, this study focused on social attention, affective arousal and empathy. Seventeen adults with XXY and 20 non-clinical controls participated in this study. Eyetracking was used to investigate social attention, as expressed in visual scanning patterns in response to the viewing of empathy evoking video clips. Skin conductance levels, reflecting affective arousal, were recorded continuously during the clips as well. Empathic skills, i.e. participants' understanding of own and others' emotions in response to the clips was also assessed. Results showed reduced empathic understanding, decreased visual fixation to the eye region, but increased affective arousal in individuals with Klinefelter syndrome. We conclude that individuals with XXY tend to avoid the eye region. Considering the increased affective arousal, we speculate that this attentional deployment strategy may not be sufficient to successfully downregulate affective hyper-responsivity. As increased affective arousal was related to reduced empathic ability, we hypothesize that own affective responses to social cues play an important role in difficulties in understanding the feelings and intentions of others. This knowledge may help in the identification of risk factors for psychopathology and targets for treatment.
    PLoS ONE 01/2014; 9(1):e84721. DOI:10.1371/journal.pone.0084721 · 3.23 Impact Factor
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