Library - The Association for X and Y Chromosome Variations

Psychotropic Medication Use in 48,XXYY Syndrome

Article Title: Psychotropic Medication Use in 48,XXYY Syndrome

Authors: Dreyer, Howell, Bothwell, Molison, Carl, Swenson, Davis, Decker, GALAXY consortia, and Tartaglia

Date of Publication: March 22, 2025

“While clinical guidelines for all neurodevelopmental and behavioral diagnoses generally include therapies paired with medication management when indicated, there are no guidelines to inform management of behavior and mental health challenges in 48,XXYY specifically (Blumling et al. 2020). Clinicians must rely on general guidelines for these patients, even though pathological features are distinct and differences specific to 48,XXYY may lead to variances in responses to pharmacotherapy.

To begin to address this gap, we conducted a study of psychotropic medication use and response to help guide pharmacological
management of behavioral and mental health symptoms in individuals with 48,XXYY.”

Rick Frith2026-03-11T13:52:34-04:00Categories: 48,XXYY|Tags: Medications, Mental health|

Demographic Composition of Participants in Sex Chromosome Aneuploidy Studies Across the Globe: A 20-Year Systematic Review

Article Title: Demographic Composition of Participants in Sex Chromosome Aneuploidy Studies Across the Globe: A 20-Year Systematic Review

Authors: Swenson, Bothwell, Zhivotov, Sieverts, Devireddy, Shuff, Nocon, Carl, Molison, Grzybacz, Avila, Ikomi, Cohen, Svoboda, and Davis

Date of Publication: October 7, 2025

“This systematic review reveals persistent gaps in the demographic reporting and representation of participants in SCA research. Even in the United States, where population diversity is high, published studies do not reflect the expected racial, ethnic, and socioeconomic makeup of affected individuals. To ensure that research findings are equitable and clinically relevant, future studies should adopt standardized demographic reporting and prioritize inclusive enrollment strategies to reflect the full spectrum of individuals with SCAs.”

Unveiling Psychiatric Complexities in 48,XXYY Syndrome: A Case Study

Article Title: Unveiling Psychiatric Complexities in 48,XXYY Syndrome: A Case Study

Authors: Francisco, Spar, and Napalinga

Date of Publication: August 22, 2025

“This case explores some of the comorbid psychiatric conditions considered in this patient’s presentations and reviews the existing literature to contemplate the differential diagnosis. The individual in this case exhibited behaviors linked to ASD or underlying personality disorder traits that initially complicated treatment, but with increasing familiarity and collateral history, appropriate recommendations were made. 48,XXYY syndrome warrants further interest, as it has had limited coverage in the literature. It would be valuable to examine how this patient’s psychiatric profile compares to those of patients with other extra X or Y chromosome syndromes.”

Rick Frith2026-02-04T13:34:40-05:00Categories: 48,XXYY|Tags: Anxiety, Autism Spectrum Disorder, Depression|

Hypopituitarism and Rathke’s Cleft Cyst in 48,XXYY Syndrome: New Insights Into Sex Chromosome Aneuploidies

Article Title: Hypopituitarism and Rathke’s cleft cyst in 48,XXYY Syndrome: new insights into sex chromosome aneuploidies

Authors: Batista, Nakaguma, Tavares, Batatinha, Nishi, Domenice, Padula, and Mendonca

Date of Publication: June 9, 2025

“The association between 48,XXYY syndrome and Rathke’s cleft cyst raises intriguing questions about the potential links between sex chromosome aneuploidies and pituitary abnormalities. This report emphasizes the need for comprehensive endocrine and structural assessments to optimize patient outcomes by contributing to the limited literature on 48,XXYY syndrome.”

Rick Frith2026-02-04T13:56:55-05:00Categories: 47,XXY (Klinefelter), 48,XXYY, Other Variations|Tags: Hypopituitarism, Rathke’s cleft cyst|

DNA hypomethylation at specific CG-sites within TRAK1 is linked to the neurocognitive profile in Klinefelter syndrome

Article Title: DNA hypomethylation at specific CG-sites within TRAK1 is linked to the neurocognitive profile in Klinefelter syndrome

Authors: Tallaksen, Hasselholm, Berletch, Filippova, Deng, Van Dyke, MacDonald, Bammler, Chang, Buskbjerg, Gravholt, Disteche, Just, and Skakkebæk

Date of Publication: September 30, 2025

“Here, we present a comprehensive and integrative analysis of the neurocognitive profile and the methylome in KS, aiming to investigate the link between specific neurocognitive traits (processing speed, working memory, visual performance, verbal memory and learning, verbal fluency and comprehension, verbal performance, and executive functions) and DNA methylation patterns, and to identify potential epigenetic biomarkers of neurocognitive function in KS.”

Rick Frith2025-12-02T16:32:44-05:00Categories: 47,XXY (Klinefelter)|Tags: DNA methylation, Neurodevelopment|

Epigenetic age acceleration in Turner and Klinefelter syndrome: Correlations with clinical aging markers

Article Title: Epigenetic age acceleration in Turner and Klinefelter syndrome: Correlations with clinical aging markers

Authors: Hasselholm, Just, Chang, Skakkebæk, and Gravholt

Date of Publication: September 1, 2025

“We demonstrated that biological aging was clearly increased in sex chromosome aneuploidies, especially TS, potentially contributing to the severely reduced lifespan. Additionally, unfavorable changes in body composition, common in both TS and KS, and in particular in the presence of hypogonadism, could result in accelerated aging—or be the result thereof.”

Rick Frith2025-12-02T16:11:13-05:00Categories: 47,XXY (Klinefelter)|Tags: Aging, DNA methylation, Epigenetic age, Turner syndrome|

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|

Metabolism and Type 2 Diabetes Across Life Stages in Klinefelter Syndrome: A Population-based Cohort Study

Article Title: Metabolism and Type 2 Diabetes Across Life Stages in Klinefelter Syndrome: A Population-based Cohort Study

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

Date of Publication: 2025

“The metabolic profile in men with KS is dependent on diagnosis and treatment status, with pronounced metabolic dysfunction in U-KS [undiagnosed Klinefelter syndrome]. Better diagnosis and treatment of KS are needed to alleviate metabolic dysfunction and improve survival in men with KS.”

Rick Frith2025-12-03T12:40:10-05:00Categories: 47,XXY (Klinefelter)|Tags: Diabetes, Metabolism|

Continuity of Care in KS: Age-Adapted Modules for Standardized Clinical Data Collection

Article Title: Continuity of Care in Klinefelter Syndrome: Age-Adapted Modules for Standardized Clinical Data Collection (I-KS)

Authors: Grasemann, Gravholt, Breen, Aksglaede, Lucas-Herald, Alimussina, Boettcher, Wernsmann, Bauer, Bryce, Carlomagno, Hannema, Isidori, Mazen, Nordenstroem, and Ahmed

Date of Publication: September 25, 2025

“The structured templates aim to support healthcare professionals in providing comprehensive, age-appropriate care while enabling systematic data collection for research. These modules provide a framework for tracking key clinical parameters during the transition from pediatric to adult care, ensuring continuity and optimizing long-term health outcomes for individuals with KS. Implementation of these modules in clinical registries will facilitate pooled analyses, helping to address unresolved clinical questions and improve care across the lifespan.”

Rick Frith2025-10-07T14:37:38-04:00Categories: 47,XXY (Klinefelter)|Tags: Data collection|