Prevalence, diagnostic features, and medical outcomes of females with Turner syndrome with a trisomy X cell line (45,X/47,XXX): Results from the InsighTS Registry

Natalia Klamut, Department of Pediatrics, University of Colorado School of Medicine, Colorado, Aurora, USA.
Samantha Bothwell, Department of Pediatrics, University of Colorado School of Medicine, Colorado, Aurora, USA.
Alexandra E. Carl, Department of Pediatrics, University of Colorado School of Medicine, Colorado, Aurora, USA.
Vaneeta Bamba, Division of Endocrinology, Children's Hospital of Philadelphia Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Jennifer R. Law, Division of Pediatric Endocrinology, Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Wendy J. Brickman, Department of Pediatrics, Northwestern University Feinberg School of Medicine, Turner Syndrome Program, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.
Karen O. Klein, Department of Pediatrics, University of California and Rady Children's Hospital, San Diego, California, USA.
Roopa Kanakatti Shankar, Division of Endocrinology, Children's National Hospital, The George Washington University School of Medicine, Washington, DC, USA.
Catherina T. Pinnaro, Division of Endocrinology and Diabetes, Stead Family Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA.
Patricia Y. Fechner, Department of Pediatrics, University of Washington and Division of Endocrinology, Seattle Children's Hospital, Washington, USA.
Siddharth K. Prakash, Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA.
Iris Gutmark-Little, Division of Pediatric Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Susan Howell, Department of Pediatrics, University of Colorado School of Medicine, Colorado, Aurora, USA.
Nicole Tartaglia, Department of Pediatrics, University of Colorado School of Medicine, Colorado, Aurora, USA.
Marybel Good, Turner Syndrome Global Alliance, Overland Park, Kansas, USA.
Kelly C. Ranallo, Turner Syndrome Global Alliance, Overland Park, Kansas, USA.
Shanlee M. Davis, Department of Pediatrics, University of Colorado School of Medicine, Colorado, Aurora, USA.

Document Type

Journal Article

Publication Date

7-17-2024

Journal

American journal of medical genetics. Part A

DOI

10.1002/ajmg.a.63819

Keywords

Trisomy X syndrome; Turner syndrome; mosaicism; phenotype; sex chromosome aneuploidy

Abstract

Turner syndrome (TS) is defined by partial or complete absence of a sex chromosome. Little is known about the phenotype of individuals with TS mosaic with trisomy X (45,X/47,XXX or 45,X/46,XX/47,XXX) (~3% of TS). We compared the diagnostic, perinatal, medical, and neurodevelopmental comorbidities of mosaic 45,X/47,XXX (n = 35, 9.4%) with nonmosaic 45,X (n = 142) and mosaic 45,X/46,XX (n = 66). Females with 45,X/47,XXX had fewer neonatal concerns and lower prevalence of several TS-related diagnoses compared with 45,X; however the prevalence of neurodevelopmental and psychiatric diagnoses were not different. Compared to females with 45,X/46,XX, the 45,X/47,XXX group was significantly more likely to have structural renal anomalies (18% vs. 3%; p = 0.03). They were twice as likely to have congenital heart disease (32% vs. 15%, p = 0.08) and less likely to experience spontaneous menarche (46% vs. 75% of those over age 10, p = 0.06), although not statistically significant. Congenital anomalies, hypertension, and hearing loss were primarily attributable to a higher proportion of 45,X cells, while preserved ovarian function was most associated with a higher proportion of 46,XX cells. In this large TS cohort, 45,X/47,XXX was more common than previously reported, individuals were phenotypically less affected than those with 45,X, but did have trends for several more TS-related diagnoses than individuals with 45,X/46,XX.

Department

Pediatrics

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