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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    • "Bishop et al. (2011) documented that 2 of nineteen 47,XXY boys (11%) had a diagnosis of autism spectrum disorders (ASD) in their prenatal follow-up sample. Based on clinical screening, Tartaglia et al. (2010) found that 1 of twenty 47,XXY boys (5%) met full criteria for ASD. This increased vulnerability for autism symptomatology illustrates that social development may be compromised in several individuals with 47,XXY. "
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    ABSTRACT: Boys and men with an extra X chromosome (47,XXY, Klinefelter syndrome) are at risk for problems in social functioning and have an increased vulnerability for autism spectrum disorders (ASD). In the search for underlying mechanisms driving this increased risk, this study focused on social attention, that is, spontaneous orientation toward facial expressions. Seventeen adults with 47,XXY and 20 non-clinical controls participated in this study. Social attention was measured using an eyetracking method that quantifies the visual scanning patterns of faces expressing different types of emotions (happy, fearful, angry, neutral) and their varying intensity levels (25%, 50%, 75%, 100%). Overall, the group with Klinefelter syndrome fixated less on the eye region of faces when compared to controls (Cohen’s d 1.4), and did not show the typical tendency, as was found in the control group, to first fixate on the eyes when presented with a face (Cohen’s d 1.0). There was no significant effect of type or intensity of emotion. Shorter looking times toward eyes showed a borderline significant correlation with self-reports of poorer social functioning, with 29% explained variance. These findings suggest a reduced tendency to rapidly and automatically attend to the eyes of others in individuals with 47,XXY. This may have impact on more complex social-cognitive abilities that build upon this. In addition to studies of behaviorally defined disorders such as ASD, studying individuals with Klinefelter syndrome provide insight into mechanisms underlying various “at risk” pathways of social dysfunction and the factors that mediate this risk. ( JINS , 2015, 21 , 364–372)
    Full-text · Article · May 2015 · Journal of the International Neuropsychological Society
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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.
    Full-text · Article · Aug 2014
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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.
    Full-text · Article · Apr 2014 · Frontiers in Neuroendocrinology
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