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

Authors

Natalia Klamut
Samantha Bothwell
Alexandra E Carl
Vaneeta Bamba
Jennifer R Law
Wendy J Brickman
Karen O Klein
Roopa Kanakatti Shankar
Catherina T Pinnaro
Patricia Y Fechner
Siddharth K Prakash
Iris Gutmark-Little
Susan Howell
Nicole Tartaglia
Marybel Good
Kelly C Ranallo
Shanlee M Davis

Language

English

Publication Date

12-1-2024

Journal

American Journal of Medical Genetics Part A

DOI

10.1002/ajmg.a.63819

PMID

39016627

PMCID

PMC11540750

PubMedCentral® Posted Date

12-1-2025

PubMedCentral® Full Text Version

Author MSS

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.

Keywords

Humans, Turner Syndrome, Female, Chromosomes, Human, X, Trisomy, Mosaicism, Prevalence, Registries, Adult, Adolescent, Sex Chromosome Aberrations, Child, Phenotype, Child, Preschool, Sex Chromosome Disorders of Sex Development, Young Adult, Infant, Infant, Newborn, Heart Defects, Congenital, Turner syndrome, Trisomy X syndrome, sex chromosome aneuploidy, mosaicism, phenotype

Published Open-Access

yes

Recommended Citation

Klamut, Natalia; Bothwell, Samantha; Carl, Alexandra E; et al., "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" (2024). Faculty, Staff and Student Publications. 6447.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6447