A multicenter analysis of individuals with a 47,XXY/46,XX karyotype.
Document Type
Article
Publication Date
10-2024
Identifier
DOI: 10.1016/j.gim.2024.101212
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.
Journal Title
Genetics in medicine : official journal of the American College of Medical Genetics
Volume
26
Issue
10
First Page
101212
Last Page
101212
MeSH Keywords
Humans; Male; Klinefelter Syndrome; Female; Retrospective Studies; Adult; Karyotype; Adolescent; Phenotype; Child; Karyotyping; Aneuploidy; Child, Preschool; Chromosomes, Human, X; Young Adult; Infant; Sex Chromosome Aberrations
Keywords
47,XXY/46,XX karyotype; Difference of sex development; Klinefelter syndrome; Ovotestes; Sex chromosome aneuploidy
Recommended Citation
Guess T, Wheeler FC, Yenamandra A, et al. A multicenter analysis of individuals with a 47,XXY/46,XX karyotype. Genet Med. 2024;26(10):101212. doi:10.1016/j.gim.2024.101212
COinS
