47,XYY Archives - The Association for X and Y Chromosome Variations

Generating Advancements in Longitudinal Analysis in X and Y Variations

Article Title: Generating Advancements in Longitudinal Analysis in X and Y Variations: Rationale, Methods, and Diagnostic Characteristics for the GALAXY Registry

Authors: Carl, Bothwell, Swenson, Bregante, Cohen, Cover, Dawczyk, Decker, Gerken, Hong, Howell, Raznahan, Rogol, Tartaglia, and Davis

Date of Publication: July 26, 2025

“Sex chromosome aneuploidies (SCAs) are a family of genetic disorders that result from an atypical number of X and/or Y chromosomes. SCAs are the most common chromosomal abnormality, affecting ~1/400 live births, yet are often underdiagnosed, leading to over-representation of more severely impacted individuals in many clinical studies. In addition to this ascertainment bias, existing work in SCAs has also been limited by low geographic and demographic diversity. To address these limitations, we have created the Generating Advancements with Longitudinal Analysis in X and Y variations (GALAXY) Registry. Through prioritizing sustainability, transparency, and minimizing participant burden, the overarching goal of the GALAXY Registry is to improve health outcomes for individuals with SCAs by serving as an infrastructure for future SCA research based on a large, heterogeneous, and longitudinal sample. To date, GALAXY has accrued 335 verified SCA participants with an average accrual of 11.2 participants/month (6.7 47,XXY, 1.9 47,XXX, 2.0 47,XYY, 3.2 48,XXYY, 1.8 48,XXXY, and 1.3 Other). Demographic data between those identified to have SCA prenatally (predominantly cell-free DNA screening) differ from those diagnosed postnatally for insurance status, age at enrollment, genetic test type, and reason for SCA diagnosis. Next steps include targeted recruitment of underrepresented groups (e.g., non-47, XXY karyotypes, older adults, minoritized individuals), extraction of medical record data into the registry, international expansion, and continued engagement with the SCA community. As a collaboration between clinician investigators and the SCA community, the GALAXY Registry is a powerful resource for future patient-centered clinical research.”

Rick Frith2025-08-14T14:42:05-04:00Categories: 47,XXX (trisomy x), 47,XXY (Klinefelter), 47,XYY, 48,XXXY, 48,XXYY, All Variations, Mosaicism, Other Variations|Tags: GALAXY|

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|

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|

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|

Sex chromosome aneuploidies and fertility: 47,XXY, 47,XYY, 47,XXX and 45,X/47,XXX

Article title: Sex chromosome aneuploidies and fertility: 47,XXY, 47,XYY, 47,XXX and 45,X/47,XXX

Author: Alan D. Rogol

Date of Publication: August 1, 2023

“Assisted reproductive technology, especially micro-testicular sperm extraction, has an important role, especially for those with 47,XXY; however, more recent data show promising techniques for the in vitro maturation of spermatogonial stem cells and 3D organoids in culture. Assisted reproductive technology is more complex for the female, but vitrification of oocytes has shown promising advances.”

Rick Frith2023-11-21T16:09:37-05:00Categories: 47,XXX (trisomy x), 47,XXY (Klinefelter), 47,XYY, Mosaicism|Tags: Assisted Reproductive Technology, Fertility, In Vitro|

Sex Chromosome Dosage Effects on White Matter

Article Title: Sex Chromosome Dosage Effects on White Matter

Authors: Warling, Yavi, Clasen, Blumenthal, Lalonde, Raznahan, and Liu

Date of Publication: June 12, 2021

“These findings represent the most complete maps of X- and Y-chromosome effects on human white matter to date, and show how such changes connect to psychopathological symptoms and gray matter anatomy.”

Rick Frith2023-09-05T14:53:57-04:00Categories: 47,XXX (trisomy x), 47,XXY (Klinefelter), 47,XYY, 48,XXYY, Other Variations|Tags: Neuroimaging, White Matter|

Eosinophilic esophagitis in individuals with sex chromosome aneuploidies: Clinical presentations and management implications

Article Title: Eosinophilic esophagitis in individuals with sex chromosome aneuploidies: Clinical presentations and management implications

Authors: Howell, Buchanan, Davis, Miyazawa, Furuta, Tartaglia, and Nguyen

Date of Publication: September 9, 2021

“The findings of this chart review demonstrate the importance for the community affected by SCA conditions to have an increased awareness of the variable presentations of eosinophilic esophagitis (including coping strategies), especially among different age groups and in the context of neurodevelopmental problems, the need for specific screening for EoE symptoms, and referral to GI for evaluation and treatment. Such clinical knowledge and action can facilitate diagnosing EoE as early as possible and improve quality of life, symptom management, and limit progression of severity for patients.”

Rick Frith2023-09-05T14:41:27-04:00Categories: 47,XXX (trisomy x), 47,XXY (Klinefelter), 47,XYY, 48,XXXY, 48,XXYY, Mosaicism|Tags: Eosinophilic Esophagitis|

Association of Supernumerary Sex Chromosome Aneuploidies With Venous Thromboembolism

Article Title: Association of Supernumerary Sex Chromosome Aneuploidies With Venous Thromboembolism

Authors: Berry, Finucane, Myers, Abril, Kirchner, Ledbetter, Martin, and Oetjens

Date of Publication: January 17, 2023

“Adults with supernumerary sex chromosome aneuploidies compared with 2 sex chromosomes had a small but statistically significant increased risk of VTE. Further research is needed to understand the clinical implications of this association.”

Rick Frith2024-08-19T16:56:14-04:00Categories: 47,XXX (trisomy x), 47,XXY (Klinefelter), 47,XYY|Tags: thromboembolism, VTE|

Understanding the phenotypic spectrum and family experiences of XYY syndrome: Important considerations for genetic counseling

Article Title: Understanding the phenotypic spectrum and family experiences of XYY syndrome: Important considerations for genetic counseling

Authors: Jodarski, Duncan, Torres, Gore, Raznahan, and Similuk

Date of Publication: January 7, 2023

“XYY syndrome is a diagnosis that has significant implications on not only the affected individual, but the family as well. It is therefore imperative that HCPs fully understand the range of lived experiences with XYY so that we can better counsel and care for affected individuals and their families.”

Rick Frith2023-04-13T11:03:45-04:00Categories: 47,XYY|Tags: Genetic counseling, Neurodevelopment, Psychosocial|