A multi-center analysis of individuals with a 47,XXY/46,XX karyotype

Tiffany Guess, Molecular Pathology Laboratory Network, Maryville, TN; Department of Pathology, Vanderbilt University Medical Center, Nashville, TN. Electronic address: tguess@mplnet.com.
Ferrin C. Wheeler, Department of Pathology, Vanderbilt University Medical Center, Nashville, TN.
Ashwini Yenemandra, Department of Pathology, Vanderbilt University Medical Center, Nashville, TN.
Samantha L. Schilit, Division of Clinical Cytogenetics, Center for Advanced Molecular Diagnostics, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Hannah S. Anderson, ARUP Laboratories, Salt Lake City, UT; Department of Human Genetics, University of Utah, Salt Lake City, UT.
Kathleen M. Bone, Department of Pathology, Medical College of Wisconsin, Milwaukee, WI.
Billie Carstens, Colorado Genetics Laboratory, Department of Pathology, University of Colorado, Anschutz Medical Center, Aurora, CO.
Laura Conlin, Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, PA.
Matthew C. Dulik, Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, PA.
Barbra R. Dupont, Greenwood Genetic Center, Greenwood, SC.
Elizabeth Fanning, Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, PA.
Juli-Anne Gardner, Department of Pathology and Laboratory Medicine, University of Vermont Medical Center, Burlington, VT.
Mary Haag, Colorado Genetics Laboratory, Department of Pathology, University of Colorado, Anschutz Medical Center, Aurora, CO.
Benjamin A. Hilton, Greenwood Genetic Center, Greenwood, SC.
Jill Johnson, Greenwood Genetic Center, Greenwood, SC.
Jillene Kogan, Advocate Health - MidwestFollow
Jacyln Murry, Johns Hopkins University School of Medicine, Baltimore, MD.
Katarzyna Polonis, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
Denise I. Quigley, ARUP Laboratories, Salt Lake City, UT.
Elena A. Repnikova, Department of Pathology and Laboratory Medicine, Children's Mercy Hospital Kansas City, MO.
Ross A. Rowsey, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
Nancy Spinner, Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, PA.
Mikayla Stoeker, Colorado Genetics Laboratory, Department of Pathology, University of Colorado, Anschutz Medical Center, Aurora, CO.
Virginia Thurston, Atrium Health, Charlotte, NC.
Margaret Wiley, GeneDx Sema4, Stamford, CT.
Lei Zhang, Department of Pathology and Laboratory Medicine, Children's Mercy Hospital Kansas City, MO.

Affiliations

Advocate Clinical Laboratories, Rosemont

Abstract

Introduction:Klinefelter syndrome (KS), a sex chromosome aneuploidy, 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, multi-center 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 5-98% 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, two patients were assigned female sex at birth DISCUSSION: 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 FISH 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.

Document Type

Article

PubMed ID

39011769

Teammate Access


 

Share

COinS