Epigenetics and genomics in Klinefelter syndrome

Article Title: Epigenetics and genomics in Klinefelter syndrome

Authors: Skakkebæk, Viuff, Nielsen, and Gravholt

Date of Publication: June 2, 2020

“Since the first description of Klinefelter syndrome (KS) was published in 1942 in The Journal of Clinical Endocrinology, large inter‐individual variability in the phenotypic presentation has been demonstrated. However, our understanding of the global impact of the additional X chromosome on the genome remains an enigma. Evidence from the existing literature of KS indicates that not just one single genetic mechanism can explain the phenotype and the variable expressivity, but several mechanisms may be at play concurrently. In this review, we describe different genetic mechanisms and recent advances in the understanding of the genome, epigenome, and transcriptome of KS and the link to the phenotype and clinical heterogeneity. Future studies are needed to unite clinical data, genomic data, and basic research attempting to understand the genetics behind KS. Unraveling the genetics of KS will be of clinical relevance as it may enable the use of polygenic risk scores to predict future disease susceptibility and enable clinical risk stratification of KS patients in the future.”

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2021-03-03T15:01:38-05:00Categories: 47,XXY (Klinefelter)|

What microRNAs could tell us about the human X chromosome

Article Title: What microRNAs could tell us about the human X chromosome

Authors: Di Palo, Siniscalchi, Salerno, Russo, Gravholt and Potenza

Date of Publication: April 30, 2020

“MicroRNAs (miRNA) are small-non coding RNAs endowed with great regulatory power, thus playing key roles not only in almost all physiological pathways, but also in the pathogenesis of several diseases. Surprisingly, genomic distribution analysis revealed the highest density of miRNA sequences on the X chromosome; this evolutionary conserved mammalian feature equips females with a larger miRNA machinery than males. However, miRNAs contribution to some X-related conditions, properties or functions is still poorly explored. With the aim to support and focus research in the field, this review analyzes the literature and databases about X-linked miRNAs, trying to understand how miRNAs could contribute to emerging gender-biased functions and pathological mechanisms, such as immunity and cancer. A fine map of miRNA sequences on the X chromosome is reported, and their known functions are discussed; in addition, bioinformatics functional analyses of the whole X-linked miRNA targetome (predicted and validated) were performed. The emerging scenario points to different gaps in the knowledge that should be filled with future experimental investigations, also in terms of possible implications and pathological perspectives for X chromosome aneuploidy syndromes, such as Turner and Klinefelter syndromes.”

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Social Management Training in Males With 47,XXY (Klinefelter Syndrome)

Article Title: Social Management Training in Males With 47,XXY (Klinefelter Syndrome): A Pilot Study of a Neurocognitive-Behavioral Treatment Targeting Social, Emotional, and Behavioral Problems

Authors: Martin, Van Rijn, Bierman, and Swaab

Date of Publication: January 1, 2021

“Klinefelter syndrome (47,XXY) is associated with problems in social interaction and behavioral adaptation. Sixteen adolescents and adult men with 47,XXY enrolled in a pilot study evaluating the effectiveness of Social Management Training (SMT), a novel neurocognitive-behavioral treatment program targeted at improving social, emotional, and behavioral functioning. Participants reported improved emotional stability from pre- to post-test (5 months). Informants reported reductions in internalizing and externalizing symptoms, including improvement in self-regulation. Although informants did not report changes in autism-like symptoms, increased awareness of social challenges was found. SMT may improve emotional stability, self-regulation, and self-reflection in people males with Klinefelter syndrome. This potentially efficacious treatment approach may prove to be a promising psychosocial therapeutic intervention for this population.”

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2021-01-27T16:08:22-05:00Categories: 47,XXY (Klinefelter)|

From mini‐puberty to pre‐puberty: early impairment of the hypothalamus-pituitary-gonadal axis (KS)

Article Title: From mini‐puberty to pre‐puberty: early impairment of the hypothalamus-pituitary-gonadal axis with normal testicular function in children with non-mosaic Klinefelter syndrome

Authors: Spaziani, Granato, Liberati, Rossi, Tahani, Pozza, Gianfrilli, Papi, Anzuini, Lenzi, Tarani, and Radicioni

Date of Publication: May 6, 2020

Purpose Klinefelter syndrome (KS) is a genetic disorder caused by the presence of an extra X chromosome in males. The aim of this study was to evaluate the hypothalamic–pituitary–gonadal (HPG) axis and the clinical profile of KS boys from mini-puberty to early childhood…Conclusions No hormonal signs of tubular or interstitial damage were found in KS infants. The presence of higher levels of gonadotropins, INHB and testosterone during mini-puberty and pre-puberty may be interpreted as an alteration of the HPG axis in KS infants.”

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2021-01-14T11:18:32-05:00Categories: 47,XXY (Klinefelter)|

A review of neurocognitive functioning of children with sex chromosome trisomies

Article Title: A review of neurocognitive functioning of children with sex chromosome trisomies: Identifying targets for early intervention

Authors: Van Rijn, Urbanus, and Swaab

Date of Publication: July 2, 2019

“Results of the reviewed studies show that although traditionally, the focus has been on language and intelligence (IQ) in this population, recent studies suggest that executive functioning and social cognition may also be significantly affected already in childhood. These findings suggest that neuropsychological screening of children diagnosed with SCT should be extended, to also include executive functioning and social cognition. Knowledge about these neurocognitive risks is important to improve clinical care and help identify targets for early support and intervention programs to accommodate for the needs of individuals with SCT.”

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2021-01-13T13:26:28-05:00Categories: 47,XXX (trisomy x), 47,XXY (Klinefelter), 47,XYY|Tags: |

The behavioral profile of children aged 1–5 years with sex chromosome trisomy

Article Title: The behavioral profile of children aged 1–5 years with sex chromosome trisomy (47,XXX, 47,XXY, 47,XYY)

Authors: Van Rijn, Tartaglia, Urbanus, Swaab, and Cordeiro

Date of Publication: May 20, 2020

“Collectively, these results demonstrate the importance of behavioral screening for behavioral problems in routine clinical care for children with SCT from a young age. Social–emotional problems may require special attention, as these problems seem most prominent, showing increased risk across the full age range, and with these problems occurring regardless of the timing of diagnosis, and across all three SCT karyotypes.”

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2021-01-07T16:31:23-05:00Categories: 47,XXX (trisomy x), 47,XXY (Klinefelter), 47,XYY|

Infertility considerations in Klinefelter syndrome: From origin to management

Article Title: Infertility considerations in Klinefelter syndrome: From origin to management

Authors: Deebel, Bradshaw, and Sadri-Ardekani

Date of Publication: December 15, 2020

“Klinefelter syndrome (KS) is defined as the presence of one or more extra “X” chromosome in a male patient. It affects approximately    1 in 600 newborn males and the most common chromosomal abnormality, leading to male hypogonadism and infertility. There is a lack of data supporting best practices for KS patients’ care. In this paper we review controversial issues in KS research ranging from mechanisms of variation in KS phenotype to abnormalities resulting in reduced sperm production to successful sperm retrieval disparities after testicular sperm extraction (TESE). Translation to live birth and offspring health is also examined. Finally, medical therapies used to optimize the hormonal status and chances of fertility in KS patients are reviewed. We will also discuss the experimental spermatogonial stem cell (SSC) treatments, which are considered the future for TESE negative patients.”

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2020-12-30T16:38:11-05:00Categories: 47,XXY (Klinefelter)|Tags: |

Klinefelter syndrome (KS): genetics, clinical phenotype and hypogonadism

Article Title: Klinefelter syndrome (KS): genetics, clinical phenotype and hypogonadism

Authors: Bonomi, Rochira, Pasquali, Balercia, Jannini, and Ferlin

Date of Publication: September 19, 2016

“Klinefelter Syndrome (KS) is characterized by an extreme heterogeneity in its clinical and genetic presentation. The relationship between clinical phenotype and genetic background has been partially disclosed; nevertheless, physicians are aware that several aspects concerning this issue are far to be fully understood. By improving our knowledge on the role of some genetic aspects as well as on the KS, patients’ interindividual differences in terms of health status will result in a better management of this chromosomal disease. The aim of this review is to provide an update on both genetic and clinical phenotype and their interrelationships.”

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2020-12-30T15:51:44-05:00Categories: 47,XXY (Klinefelter)|

Strategies to improve early diagnosis of Klinefelter syndrome

Article Title: Strategies to improve early diagnosis of Klinefelter syndrome

Authors: Alberto Ferlin

Date of Publication: October 2020

“Klinefelter syndrome is the most frequent chromosome disorder in men, but it is largely undiagnosed or receives a late diagnosis in adulthood. This condition is characterized by an extra X-chromosome: approximately 80%-90% of patients with Klinefelter syndrome have a 47,XXY karyotype, 10%-20% mosaicisms of two different genetic lines such as 47,XXY/46,XY, isochromosome X, and higher number of X chromosomes. Although our knowledge on this syndrome substantially improved in last years, the diagnostic rate is still low. It has been estimated that only 25% to 40% of subjects with 47,XXY Klinefelter syndrome are ever diagnosed. A prenatal diagnosis is made in 15–20% of these cases, 10% is diagnosed before puberty, 15% at puberty, and the remaining 50–60% of cases are diagnosed during adulthood, typically in the course of a fertility workup, with some cases diagnosed even after the age of 50 or 60 years. Variants with higher number of X chromosomes (48,XXXY and 49,XXXXY) have more severe phenotype and distinct clinical features, which leads to higher diagnostic rate than 47,XXY. This manuscript refers to the most common form 47,XXY syndrome and strategies to improve early and timely diagnosis.”

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2020-12-23T15:26:48-05:00Categories: 47,XXY (Klinefelter)|
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