Psychological functioning, brain morphology, and functional neuroimaging in Klinefelter syndrome

Skakkebæk, Anne; Gravholt, Claus Højbjerg; Chang, Simon; Moore, P.J.; Wallentin, Mikkel

doi:10.1002/ajmg.c.31806

Cited by 15 publications

(12 citation statements)

References 108 publications

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“…Patients with KS might have also exhibit impairments in executive functions related to attention, flexibility and planning as well as response inhibition 158 . The risks of developing psychiatric conditions, such as schizophrenia, bipolar disorders, depression, anxiety, autism and ADHD are increased in patients with KS 159‐163 …”

Section: Clinical Pictures Diagnostic Steps and Therapymentioning

confidence: 99%

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European academy of andrology guidelines on Klinefelter Syndrome Endorsing Organization: European Society of Endocrinology

et al. 2020

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Background Knowledge about Klinefelter syndrome (KS) has increased substantially since its first description almost 80 years ago. A variety of treatment options concerning the spectrum of symptoms associated with KS exists, also regarding aspects beyond testicular dysfunction. Nevertheless, the diagnostic rate is still low in relation to prevalence and no international guidelines are available for KS. Objective To create the first European Academy of Andrology (EAA) guidelines on KS. Methods An expert group of academicians appointed by the EAA generated a consensus guideline according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system. Results Clinical features are highly variable among patients with KS, although common characteristics are severely attenuated spermatogenesis and Leydig cell impairment, resulting in azoospermia and hypergonadotropic hypogonadism. In addition, various manifestations of neurocognitive and psychosocial phenotypes have been described as well as an increased prevalence of adverse cardiovascular, metabolic and bone‐related conditions which might explain the increased morbidity/mortality in KS. Moreover, compared to the general male population, a higher prevalence of dental, coagulation and autoimmune disorders is likely to exist in patients with KS. Both genetic and epigenetic effects due to the supernumerary X chromosome as well as testosterone deficiency contribute to this pathological pattern. The majority of patients with KS is diagnosed during adulthood, but symptoms can already become obvious during infancy, childhood or adolescence. The paediatric and juvenile patients with KS require specific attention regarding their development and fertility. Conclusion These guidelines provide recommendations and suggestions to care for patients with KS in various developmental stages ranging from childhood and adolescence to adulthood. This advice is based on recent research data and respective evaluations as well as validations performed by a group of experts.

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Section: Clinical Pictures Diagnostic Steps and Therapymentioning

confidence: 99%

“…In addition, the effects of anti-osteoporotic drugs on BMD and fracture risk in KS have not been studied. [159][160][161][162][163] Psychosexual development is often delayed and sexual problems might be more frequent in KS. 164 Most patients identify as male, but gender incongruence in KS has been reported in some studies.…”

Section: Evidencementioning

confidence: 99%

European academy of andrology guidelines on Klinefelter Syndrome Endorsing Organization: European Society of Endocrinology

et al. 2020

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“…The total brain volume in KS is smaller than that in TD ( 322 ), with smaller volumes in the insula, frontal and temporal lobes, and subcortical regions, such as the amygdala, hippocampus ( 16 , 51 , 94 , 95 ), and cerebellum (see Section 3.2.1). In contrast, the sensorimotor and parietal-occipital areas are enlarged, and the white matter volumes of the left cuneus and precuneus are the most robust, and extending to the inferior parietal regions in some cases ( 152 , 303 , 323 ).…”

Section: Expectation Mismatch On Perceptual Input Will Lead To Uneven...mentioning

confidence: 99%

Giftedness and atypical sexual differentiation: enhanced perceptual functioning through estrogen deficiency instead of androgen excess

Sakaguchi,

Tawata

2024

Front. Endocrinol.

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Syndromic autism spectrum conditions (ASC), such as Klinefelter syndrome, also manifest hypogonadism. Compared to the popular Extreme Male Brain theory, the Enhanced Perceptual Functioning model explains the connection between ASC, savant traits, and giftedness more seamlessly, and their co-emergence with atypical sexual differentiation. Overexcitability of primary sensory inputs generates a relative enhancement of local to global processing of stimuli, hindering the abstraction of communication signals, in contrast to the extraordinary local information processing skills in some individuals. Weaker inhibitory function through gamma-aminobutyric acid type A (GABAA) receptors and the atypicality of synapse formation lead to this difference, and the formation of unique neural circuits that process external information. Additionally, deficiency in monitoring inner sensory information leads to alexithymia (inability to distinguish one’s own emotions), which can be caused by hypoactivity of estrogen and oxytocin in the interoceptive neural circuits, comprising the anterior insular and cingulate gyri. These areas are also part of the Salience Network, which switches between the Central Executive Network for external tasks and the Default Mode Network for self-referential mind wandering. Exploring the possibility that estrogen deficiency since early development interrupts GABA shift, causing sensory processing atypicality, it helps to evaluate the co-occurrence of ASC with attention deficit hyperactivity disorder, dyslexia, and schizophrenia based on phenotypic and physiological bases. It also provides clues for understanding the common underpinnings of these neurodevelopmental disorders and gifted populations.

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“… 2 3 The phenotypic spectrum of KS is wide, ranging from manifesting only as small testes and infertility to more classic traits and comorbidities, such as hypergonadotropic hypogonadism, infertility, neurocognitive deficits, psychiatric disorders, obesity, diabetes, osteoporosis, and autoimmune disorders. 4 5 6 7 8 Early diagnosis of KS and subsequent treatment and intervention, such as testosterone replacement therapy, testicular sperm extraction, early speech and occupational therapy, and educational assistance, have been shown to improve the long-term quality of life for patients with KS and alleviate later complications. 9 10 11 12 13 14 15 However, the existing data are limited, and more rigorous scientific investigations are needed.…”

Section: Introductionmentioning

confidence: 99%

Polymerase chain reaction-based assays facilitate the breeding and study of mouse models of Klinefelter syndrome

Zhang

Zhou

et al. 2022

Asian Journal of Andrology

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Klinefelter syndrome (KS) is one of the most frequent genetic abnormalities and the leading genetic cause of nonobstructive azoospermia. The breeding and study of KS mouse models are essential to advancing our knowledge of the underlying pathological mechanism. Karyotyping and fluorescence in situ hybridization are reliable methods for identifying chromosomal contents. However, technical issues associated with these methods can decrease the efficiency of breeding KS mouse models and limit studies that require rapid identification of target mice. To overcome these limitations, we developed three polymerase chain reaction-based assays to measure specific genetic information, including presence or absence of the sex determining region of chromosome Y ( Sry ), copy number of amelogenin, X-linked ( Amelx ), and inactive X specific transcripts ( Xist ) levels. Through a combined analysis of the assay results, we can infer the karyotype of target mice. We confirmed the utility of our assays with the successful generation of KS mouse models. Our assays are rapid, inexpensive, high capacity, easy to perform, and only require small sample amounts. Therefore, they facilitate the breeding and study of KS mouse models and help advance our knowledge of the pathological mechanism underlying KS.

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Psychological functioning, brain morphology, and functional neuroimaging in Klinefelter syndrome

Cited by 15 publications

References 108 publications

European academy of andrology guidelines on Klinefelter Syndrome Endorsing Organization: European Society of Endocrinology

European academy of andrology guidelines on Klinefelter Syndrome Endorsing Organization: European Society of Endocrinology

Giftedness and atypical sexual differentiation: enhanced perceptual functioning through estrogen deficiency instead of androgen excess

Polymerase chain reaction-based assays facilitate the breeding and study of mouse models of Klinefelter syndrome

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