Faculty Collaboration Database

A multicenter analysis of individuals with a 47,XXY/46,XX karyotype. Genet Med 2024 Oct;26(10):101212

Date

07/16/2024

Pubmed ID

39011769

DOI

10.1016/j.gim.2024.101212

Scopus ID

2-s2.0-85202569940 (requires institutional sign-in at Scopus site)

Abstract

PURPOSE: Klinefelter syndrome, a sex chromosome aneuploidy (SCA), is associated with a 47,XXY chromosomal complement and is diagnosed in ∼1:600 live male births. Individuals with a 46,XX cell line, in addition to 47,XXY, are less common with a limited number of published case reports.

METHODOLOGY: To better understand the implications of a 47,XXY/46,XX karyotype, we conducted a retrospective, multicenter analysis of the cytogenetic findings and associated clinical records of 34 patients diagnosed with this SCA across 14 institutions.

RESULTS: Presence of the XX cell line ranged from 5% to 98% in patient specimens. Phenotypes also exhibited significant heterogeneity with some reporting a single reason for referral and others presenting with a constellation of symptoms, including ambiguous genitalia and ovotestes. Ovotestes were present in 12% of individuals in this cohort, who had a significantly higher percentage of XX cells. Notably, 2 patients were assigned female sex at birth.

CONCLUSION: These findings highlight the variability of the clinical phenotypes associated with this SCA, as well as the challenges of clinical management for this population. Karyotype or fluorescence in situ hybridization analysis, which offer single-cell resolution, rather than chromosomal microarray or molecular testing, is the ideal test strategy in these instances as mosaicism can occur at low levels.

Author List

Guess T, Wheeler FC, Yenamandra A, Schilit SLP, Anderson HS, Bone KM, Carstens B, Conlin L, Dulik MC, Dupont BR, Fanning E, Gardner JA, Haag M, Hilton BA, Johnson J, Kogan J, Murry J, Polonis K, Quigley DI, Repnikova EA, Rowsey RA, Spinner N, Stoeker M, Thurston V, Wiley M, Zhang L

Author

Kathleen M. Bone PhD Associate Professor in the Pathology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Aneuploidy
Child
Child, Preschool
Chromosomes, Human, X
Female
Humans
Infant
Karyotype
Karyotyping
Klinefelter Syndrome
Male
Phenotype
Retrospective Studies
Sex Chromosome Aberrations
Young Adult