Non‐Invasive Prenatal Testing by Cell‐Free DNA (cfNIPT) for Detecting Turner Syndrome With Mosaicism and Structural Variants—Prenatal Findings and Postnatal Outcomes

Author:

Bedei Ivonne12ORCID,Bruder Johanna1,Lund Ida C. B.345ORCID,Thomsen Simon H.35ORCID,Vogel Ida56ORCID,Maciel‐Guerra Andrea T.7ORCID,Alvarez‐Nava Francisco89ORCID,Crenshaw Melissa L.10ORCID,Axt‐Fliedner Roland1,Gravholt Claus H.21112ORCID,Skakkebæk Anne2312ORCID

Affiliation:

1. Department of Prenatal Diagnosis and Fetal Therapy Justus‐Liebig University Gießen Germany

2. Department of Molecular Medicine Aarhus University Hospital Aarhus Denmark

3. Department of Clinical Genetics Aarhus University Hospital Aarhus Denmark

4. Department of Biomedicine Aarhus University Aarhus Denmark

5. Department of Clinical Medicine, Center for Fetal Diagnostics Aarhus University Aarhus Denmark

6. Department of Obstetrics and Gynecology Aarhus University Hospital Aarhus Denmark

7. Department of Medical Genetics and Genomic Medicine School of Medical Science State University of Campinas São Paulo Brazil

8. Facultad de Ciencias Biológicas Universidad Central del Ecuador Quito Ecuador

9. Instituto de Investigaciones Genéticas de la Universidad del Zulia Maracaibo Venezuela

10. Division of Genetics Johns Hopkins All Children's Hospital St. Petersburg Florida USA

11. Department of Endocrinology Aarhus University Hospital Aarhus Denmark

12. Department of Clinical Medicine Aarhus University Aarhus Denmark

Abstract

ABSTRACTTurner Syndrome (TS) is a sex chromosomal disorder associated with karyotype heterogeneity. Although TS can be associated with severe prenatal findings, most often linked to the 45, X karyotype, the majority of TS fetuses have no overt phenotype, resulting in delayed diagnosis and management. The objective of this study is to assess the efficacy of non‐invasive prenatal testing by cell‐free DNA (cfNIPT) in detecting TS fetuses with different TS karyotype variants and to examine the phenotypic variations and clinical outcomes.Data on pregnancies with confirmed or suspected TS from 2000 to 2024 were collected from specialists in fetal ultrasound in Germany. In addition, a small number of Danish cases with 45, X mosaicism in the placenta was included. Data were collected regarding cfNIPT results, karyotypes, prenatal ultrasound findings, and pregnancy outcomes.Of the 114 cases included, 100 (87.7%) had a high‐risk cfNIPT result for monosomy X, 53 (46.5%) were true positives (TP), and 47 (41.2%) were false positives (FP). Fourteen (12.3%) were false negatives (FN). No differences in congenital malformation or nuchal translucency were seen between TP and FN. Data on karyotype were available for 67 cases. Fourty (59.7%) had a 45, X karyotype, 16 (23.9%) 45, X mosaicism, and 11 (16.4%) had a structural variant. The 45, X karyotype was associated with a higher prevalence of congenital malformation and increased nuchal translucency (ps ≤ 0.001). The live birth rate was higher in cases with 45, X mosaicism or structural variants compared to cases with a 45, X karyotype (ps ≤ 0.03). Postnatal phenotypes were often mild.cfNIPT represents a valuable tool for the early identification of fetuses with TS karyotype variants, enabling timely intervention and targeted management. However, the high false‐positive rate underscores the need for careful counseling.

Funder

Novo Nordisk Fonden

Publisher

Wiley

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