The spectrum of the behavioral phenotype in boys and adolescents 47,XXY (Klinefelter syndrome).
ABSTRACT 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.
- SourceAvailable from: Antonella Gagliano
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- "Behavioral features are not homogeneous, including attention disorders, impaired social skills, autism spectrum symptoms, and other psychiatric disturbance . There is also a strong variability among affected individuals , from minimal to significant cognitive and behavioral disorders . When patients with KS have a normal IQ, the attention deficit could be a strong indicator of a genotype that may be otherwise unrecognized. "
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). "
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 · 7.58 Impact Factor
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- "Notably, the increased vulnerability for ASD and features in Klinefelter syndrome have been reported by several studies [Jha et al., 2007; van Rijn et al., 2008, 2012; Tartaglia et al., 2010; Bishop et al., 2011; van Rijn and Swaab, 2011; Ross et al., 2012]. Similar to Klinefelter syndrome, patients with XYY syndrome are also vulnerable to ASD, which has been reported by several studies [Gillberg et al., 1984; Nicolson et al., 1998; Kielinen et al., 2004; Bishop et al., 2011; Ross et al., 2012]. "
ABSTRACT: Autism spectrum disorders (ASD) are childhood-onset neurodevelopmental disorders characterized by verbal communication impairments, social reciprocity deficits, and the presence of restricted interests and stereotyped behaviors. Genetic factors contribute to the incidence of ASD evidently. However, the genetic spectrum of ASD is highly heterogeneous. Chromosomal abnormalities contribute significantly to the genetic deficits of syndromic and non-syndromic ASD. In this study, we conducted karyotyping analysis in a sample of 500 patients (447 males, 53 females) with ASD from Taiwan, the largest cohort in Asia, to the best of our knowledge. We found three patients having sex chromosome aneuploidy, including two cases of 47, XXY and one case of 47, XYY. In addition, we detected a novel reciprocal chromosomal translocation between long arms of chromosomes 4 and 14, designated t(4;14)(q31.3;q24.1), in a patient with Asperger's disorder. This translocation was inherited from his unaffected father, suggesting it might not be pathogenic or it needs further hits to become pathogenic. In line with other studies, our study revealed that subjects with sex chromosomal aneuploidy are liable to neurodevelopmental disorders, including ASD, and conventional karyotyping analysis is still a useful tool in detecting chromosomal translocation in patients with ASD, given that array-based comparative genomic hybridization technology can provide better resolution in detecting copy number variations of genomic DNA. © 2013 Wiley Periodicals, Inc.American Journal of Medical Genetics Part B Neuropsychiatric Genetics 10/2013; 162(7):734-41. DOI:10.1002/ajmg.b.32153 · 3.27 Impact Factor