Library - The Association for X and Y Chromosome Variations

Testosterone Effects on Short-Term Physical, Hormonal, and Neurodevelopmental Outcomes (TESTO) in Infants with 47,XXY

Article Title: Testosterone Effects on Short-Term Physical, Hormonal, and Neurodevelopmental Outcomes (TESTO) in Infants with 47,XXY

Authors: Davis, Howell, Janusz, Lahlou, Reynolds, Thompson, Swenson, Wilson, Ross, Zeitler, and Tartaglia

Date of Publication: April 3, 2025

“In this double-blind randomized controlled trial in infants with XXY, testosterone injections resulted in physical effects attributable to systemic androgen exposure, however this dose suppressed the hypothalamic-pituitary-gonadal axis. Neurodevelopment outcomes were not impacted by treatment. These results do not support routine testosterone treatment in infants with XXY, however long term follow up on physical health, neurodevelopment and testicular function is needed.”

Rick Frith2025-04-15T09:59:53-04:00Categories: 47,XXY (Klinefelter)|Tags: Early Testosterone Use, Testosterone treatment|

Cardiovascular risk and mortality in men receiving testosterone replacement therapy for KS in Denmark

Article Title: Cardiovascular risk and mortality in men receiving testosterone replacement therapy for Klinefelter syndrome in Denmark: a retrospective cohort study

Authors: Chang, Pedersen, Skakkebæk, Berglund, and Gravholt

Date of Publication: February 1, 2025

“TRT could alleviate excess mortality in KS and appears safe regarding cardiovascular risk. Today, most men with KS go undiagnosed, missing proper medical attention. There is a dire need for a policy change to ensure timely diagnosis and treatment in all men with KS.”

Rick Frith2025-02-12T12:28:55-05:00Categories: 47,XXY (Klinefelter)|Tags: Hypogonadism, Testosterone treatment|

A genome-first study of sex chromosome aneuploidies provides evidence of Y chromosome dosage effects on autism risk

Article Title: A genome-first study of sex chromosome aneuploidies provides evidence of Y chromosome dosage effects on autism risk

Authors: Berry, Finucane, Myers, Walsh, Seibert, Martin, Ledbetter, and Oetjens

Date of Publication: October 1, 2024

“In this study, we examined four SCAs in the SPARKMC-SCA cohort to explore how variations in sex chromosome dosage impact ASD risk. In our primary analysis examining the association between SCAs and ASD, we found the extra Y effect was significantly larger than the extra X effect. This conclusion was drawn from our observation that individuals with 47,XYY showed a 2.4-fold higher risk of ASD compared to those with 46,XY, and supported by our observation that individuals with 47,XXY were at a 4.6-fold higher risk compared to those with 46,XX.”

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Rick Frith2024-12-17T16:15:17-05:00Categories: 47,XXX (trisomy x), 47,XXY (Klinefelter), 47,XYY, Other Variations|Tags: Autism Spectrum Disorder, Turner syndrome|

An extra X chromosome among adult women in the Million Veteran Program: A more benign perspective of trisomy X

Article Title: An extra X chromosome among adult women in the Million Veteran Program: A more benign perspective of trisomy X

Authors: Davis, Teerlink, Lynch, Klamut, Gorman, Pagadala, Panizzon, Merritt, Genovese, Ross, and Hauger

Date of Publication: February 10, 2024

“…this study of predominately undiagnosed and aging women with 47,XXX in the MVP found differences in prevalence by genetic ancestry but few differences in sociodemographic, health, and wellbeing outcomes when compared with sex-, age-, and ancestry-matched controls. While existing trisomy X literature emphasizes an increased risk for multiple malformations and disorders among various organ systems, these studies have been conducted in clinically ascertained individuals. Overall, our results provide a more reassuring outlook for females with 47,XXX while also highlighting additional research needs.”

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Rick Frith2024-12-17T13:24:47-05:00Categories: 47,XXX (trisomy x)|

Neurocognitive and behavioral development in young children (1-7 years) with Sex Chromosome Trisomy

Article Title: Neurocognitive and behavioral development in young children (1-7 years) with Sex Chromosome Trisomy

Authors: Van Rijn, Kuiper, Bouw, Urbanus, and Swaab

Date of Publication: March 6, 2023

“Study outcomes showed early behavioral symptoms in young children with SCT, and neurocognitive vulnerabilities, already from an early age onwards. Neurobehavioral and neurocognitive difficulties tended to become more pronounced with increasing age, and were rather robust; independent of specific karyotype, pre/postnatal diagnosis or ascertainment strategy.

A more longitudinal perspective on neurodevelopmental ‘at risk’ pathways is warranted, also including studies assessing effectiveness of targeted early interventions. Neurocognitive markers that signal differences in neurodevelopment may prove to be helpful in this. Focusing on early development of language, social cognition, emotion regulation, and executive functioning may help in uncovering early essential mechanisms of (later) neurobehavioral outcome, allowing for more targeted support and early intervention.”

Rick Frith2024-08-22T16:39:02-04:00Categories: 47,XXX (trisomy x), 47,XXY (Klinefelter), 47,XYY|Tags: Behavioral phenotyping, Cognition, Social Behavior|

Evidence‑based recommendations for delivering the diagnosis of X&Y chromosome multisomies in children, adolescents, and young adults

Article Title: Evidence‑based recommendations for delivering the diagnosis of X & Y chromosome multisomies in children, adolescents, and young adults: an integrative review

Authors: Riggan, Ormond, Allyse, and Close

Date of publication: April 22, 2024

“Patient experiences suggest there should be heightened attention to diagnosis delivery, in reference to the broader ethical and social impacts of a SCM diagnosis. We present recommendations for optimal disclosure of a SCM diagnosis in early and late childhood, adolescence, and young adulthood.”

Rick Frith2024-08-13T15:03:04-04:00Categories: 47,XXX (trisomy x), 47,XXY (Klinefelter), 47,XYY, 48,XXXY, 48,XXYY, All Variations|Tags: Diagnosis delivery, genetics, multisomies|

A qualitative exploration of experiences of gender identity and gender questioning among adults with Klinefelter syndrome/XXY

Article Title: A qualitative exploration of experiences of gender identity and gender questioning among adults with Klinefelter syndrome/XXY

Authors: Harkin and Elander

Date of Publication: July 22, 2024

“The study provided novel insights into the gender identity journeys of people with KS/XXY, from early attempts to understand and make sense of gender, through dealing with social pressures, questioning gender identities, developing gender identities more congruent with feelings, and experiences of hormone replacement therapy. These new insights can inform improved treatment and care for KS/XXY people.”

Rick Frith2024-07-24T15:17:43-04:00Categories: 47,XXY (Klinefelter)|Tags: Gender identity, Gender questioning|

BMJ Best Practice – Klinefelter Syndrome

Article Title: BMJ Best Practice Klinefelter Syndrome

Authors: Alan Rogol, Gary Butler, and Claus Gravholt

Date of Publication: June 4, 2024

“Population mortality and morbidity studies suggest there is a slight but not significant lowering of life expectancy in individuals with Klinefelter syndrome (KS). The average lifespan has been found to be reduced by 1.5 to 2 years, with morbidity and mortality increased due to a wide number of conditions, including diabetes, cerebrovascular disease, and breast cancer. Higher rates of osteoporosis and fractures are also important to note.

Appropriate treatment with testosterone can alleviate the portion of excess risk that is due to conditions associated with hypergonadotropic hypogonadism, but some of the elevated risk is likely intrinsic to the chromosome aberration and therefore not corrected by testosterone treatment.

The increased morbidity and mortality in individuals with KS may also be partially explained by their often lower socioeconomic status, with cohort data suggesting shorter education, higher rates of unemployment, lower average incomes, and earlier average age at retirement compared with men without KS.

It is important to note that most boys and men with KS are never diagnosed so the reported data likely reflects more severe phenotypes of the condition.”

Rick Frith2024-06-20T14:47:40-04:00Categories: 47,XXY (Klinefelter)|Tags: Comorbidity, Fertility, Genetic testing, Gynecomastia, Hypogonadism, prenatal, Testosterone treatment|

Evidence-based recommendations for delivering the diagnosis of X&Y chromosome multisomies

Article Title: Evidence-based recommendations for delivering the diagnosis of X&Y chromosome multisomies in children, adolescents, and young adults: an integrative review

Authors: Riggan, Ormond, Allyse, and Close

Date of Publication: April 22, 2024

“Patient experiences suggest there should be heightened attention to diagnosis delivery, in reference to the broader ethical and social impacts of a SCM diagnosis. We present recommendations for optimal disclosure of a SCM diagnosis in early and late childhood, adolescence, and young adulthood.”

Rick Frith2024-05-03T14:34:44-04:00Categories: 47,XXX (trisomy x), 47,XXY (Klinefelter), 47,XYY, 48,XXYY|Tags: Diagnosis delivery|

Executive Dysfunction in Klinefelter Syndrome: Associations With Brain Activation and Testicular Failure

Article Title: Executive Dysfunction in Klinefelter Syndrome: Associations With Brain Activation and Testicular Failure

Authors: Foland-Ross, Ghasemi, Lozano Wun, Aye, Kowal, Ross, and Reiss

Date of Publication: August 18, 2023

“These findings indicate a neural basis for executive dysfunction in KS and suggest alterations in pubertal development may contribute to increased severity of this cognitive weakness. Future studies that examine whether these patterns change with testosterone replacement therapy are warranted.”

Rick Frith2023-11-29T12:03:35-05:00Categories: 47,XXY (Klinefelter)|Tags: Executive Function, Neurodevelopment|