Helpline: 1‑267‑338‑4262 | helpline@genetic.org

Help Us to Fulfill Our Mission

Helpline: 1‑267‑338‑4262 | info@genetic.org

47,XXX (trisomy x)

Quantifying the Spectrum of Early Motor and Language Milestones in Sex Chromosome Trisomy

Article Title: Quantifying the Spectrum of Early Motor and Language Milestones in Sex Chromosome Trisomy

Authors: Thompson, Bothwell, Janusz, Wilson, Howell, Davis, Swenson, Martin, Kowal, Ikomi, Despradel, Ross, and Tartaglia

Date of Publication: November 2025

“As increasing numbers of infants with prenatal SCT diagnoses present at pediatric practices, we provide an evidence-based schedule of milestone achievement in SCT as a tool for pediatricians and families. Detailed data on SCT milestones can support clinical interpretation of milestone achievement. Increased variability and later median age of milestone acquisition in SCT compared with norms support consideration of all infants with SCT as high risk.”

Rick Frith2025-11-21T12:46:14-05:00Categories: 47,XXX (trisomy x), 47,XXY (Klinefelter), 47,XYY|Tags: Developmental milestones, Early Intervention, Neurodevelopment|

Medical Findings in Infants Prenatally Identified With Sex Chromosome Trisomy in Year 1 of Life

Article Title: Medical Findings in Infants Prenatally Identified With Sex Chromosome Trisomy in Year 1 of Life

Authors: Tartaglia, Davis, Howell, Bothwell, Nocon, Kowal, Ikomi, Keene, Reynolds, Berglund, and Ross

Date of Publication: October 2025

“Results inform care as pediatricians and families can be reassured that a prenatal diagnosis of SCT is not associated with complex medical or physical abnormalities within the first year of life, but proactive monitoring for select at-risk conditions is warranted.”

Rick Frith2025-11-21T13:06:14-05:00Categories: 47,XXX (trisomy x), 47,XXY (Klinefelter), 47,XYY|Tags: Prenatal|

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.”

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.”

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

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|

The emotional journey of adapting to prenatally identified trisomy X

Article Title: The emotional journey of adapting to prenatally identified trisomy X

Authors: Thompson, Tisher, Davis, Miller, Kirk, Tartaglia, and Howell

Date of Publication: August 19, 2023

“Results suggest providers should carefully consider word choice and timing in delivery of diagnosis, and genetic counseling should provide expectant parents with current research specific to trisomy X, facilitate connections with other parents of young girls with trisomy X, introduce developmental monitoring approaches, and be prepared to support families with a range of emotional responses to the diagnosis and decisions regarding disclosure.”

Rick Frith2023-09-12T14:38:29-04:00Categories: 47,XXX (trisomy x)|Tags: Genetic counseling, NIPS, NIPT, Prenatal|