Clinical, Biochemical, and Cytogenetic Heterogeneity in Mosaic 46,XX/47,XXY Sex Chromosome Aneuploidy

NCT07885163 | Completed

• 1 other identifier: Inserm CEEI/IRB 23-134
• Study Type: observational
• Target: 257
• Locations: 1 country
• Sites: 1

Brief Summary

Mosaic sex chromosome aneuploidy 47,XXY/46,XX is an exceptionally rare variant within the spectrum of Klinefelter syndrome. Available data remain limited, especially regarding adult phenotype and long-term characteristics, and no robust comparative data with non-mosaic 47,XXY Klinefelter syndrome are currently available. This retrospective monocentric comparative study is designed to describe the clinical, biochemical, cytogenetic, gonadal, anthropometric, and socio-professional characteristics of adults with 47,XXY/46,XX mosaicism. In addition, the study is intended to compare these characteristics with those of a homogeneous cohort of individuals with non-mosaic 47,XXY Klinefelter syndrome and with previously published case reports, in order to improve phenotypic characterization of this rare chromosomal condition.

Conditions

Klinefelter Syndrome (47, XXY); Sex Chromosome Aneuploidy; Disorders of Sex Development (DSD); Sex Chromosome Disorders

Keywords

46,XX/47,XXY; Klinefelter syndrome; Sex chromosome aneuploidy; Disorders of sex development; Ovotesticular DSD; Gonadal mosaicism

Outcome Measures

Primary Outcomes (1)

• Distribution of primary gonadal phenotype in patients with 46,XX/47,XXY mosaicism

  number and percentage of participants according to primary gonadal phenotype: * bilateral testicles * unilateral testicles * unilateral ovary * unilateral or bilateral ovotestis

  Baseline

Secondary Outcomes (11)

• Correlation between XX cell-line percentage and final height within the mKS-XX cohort

  Baseline

• Between-group difference in adult height (mKS-XX vs non-mosaic KS)

  Baseline

• Between-group difference in body mass index (mKS-XX vs non-mosaic KS)

  Baseline

• Between-group difference in gonadal phenotype (mKS-XX vs non-mosaic KS)

  Baseline

• Between-group difference in testicular volume (mKS-XX vs non-mosaic KS)

  Baseline

Study Arms (2)

Individuals with 46,XX/47,XXY mosaic formula

Individuals with 46,XX/47,XXY mosaic formula Collection of clinical, demographic, anthropometric, socio-professional, hormonal and cytogenetic parameters characteristics whenever available

Individuals with homogeneous 47,XXY mosaic formula

Individuals with homogeneous 47,XXY mosaic formula Collection of clinical, demographic, anthropometric, socio-professional, hormonal and cytogenetic parameters characteristics whenever available

Eligibility Criteria

• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

patients with a diagnosis of 46,XX/47,XXY mosaicism (mKS-XX) confirmed by cytogenetic assessments

You may qualify if:

• Group A (mKS-XX):
• Minor or adult patients with a diagnosis of 46,XX/47,XXY mosaicism (mKS-XX) confirmed by two cytogenetic assessments (two karyotypes, or one karyotype plus one FISH analysis);
• Followed at Bicêtre Hospital (AP-HP, Université Paris-Saclay) in the Department of Endocrinology and Reproductive Diseases and/or the Department of Pediatric Endocrinology and Diabetology;
• Follow-up period: 2002 to 2023.
• Group B (non-mosaic KS):
• Adult patients with non-mosaic Klinefelter syndrome (47,XXY) confirmed by two cytogenetic assessments (two karyotypes, or one karyotype plus one FISH analysis);
• Followed at Bicêtre Hospital (AP-HP, Université Paris-Saclay) in the Department of Endocrinology and Reproductive Diseases;
• Follow-up period: 2002 to 2023

You may not qualify if:

• Patients who object to the use of their healthcare data for research (opt-out).
• Patients whose medical records contain insufficient, highly fragmented, or unavailable information, preventing reliable data extraction.

Sponsors & Collaborators

• Université Paris-Saclay: lead

Study Sites (1)

Bicêtre Hospital (AP-HP), Department of Endocrinology and Reproductive Diseases

Le Kremlin-Bicêtre, 94043, France

Location

Biospecimen

Retention: SAMPLES WITH DNA

Cytogenetic analyses from whole blood venous samples and cultured lymphocytes

MeSH Terms

Conditions

Klinefelter Syndrome; Disorders of Sex Development; Sex Chromosome Disorders; Ovotesticular Disorders of Sex Development

Condition Hierarchy (Ancestors)

Sex Chromosome Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chromosome Disorders; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Gonadal Disorders; Endocrine System Diseases; Hypogonadism

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: February 3, 2026
• First Posted: October 21, 2026
• Study Start: January 15, 2022
• Primary Completion: October 1, 2025
• Study Completion: January 10, 2026
• Last Updated: October 21, 2026

Record last verified: 2026-08

Locations

FR (1)