Prenatal Diagnosis of Sex Chromosome Aneuploidies: A Retrospective Study Using QF-PCR, SNP-Based Chromosomal Microarray Analysis, and NIPT

TL;DR

This study examines the detection of sex chromosome aneuploidies during pregnancy using various testing methods and highlights the limitations of non-invasive prenatal testing.

Contribution

The study provides insights into the frequency and types of sex chromosome aneuploidies and evaluates the reliability of non-invasive prenatal testing compared to invasive methods.

Findings

Turner syndrome was the most common sex chromosome aneuploidy detected.

Non-invasive prenatal testing showed limitations in detecting mosaic Turner syndrome cases.

Comprehensive genetic counseling is needed to address diagnostic uncertainties in sex chromosome aneuploidies.

Abstract

Objectives: This study aimed to characterize the types and frequencies of sex chromosome aneuploidies (SCAs) detected through invasive prenatal testing, evaluate the concordance between non-invasive prenatal testing (NIPT) and confirmatory diagnostic methods, and assess the challenges faced during genetic counseling following SCA diagnosis. Study Design: A retrospective review was conducted on 842 prenatal samples collected between 2020 and 2024 in a tertiary private medical center. Samples included amniotic fluid, chorionic villi, and products of conception. Testing involved rapid QF-PCR for aneuploidy detection, followed by SNP-based chromosomal microarray analysis (CMA). NIPT results with high risk for sex chromosomes aneuploidies were correlated with invasive testing outcomes in 19 cases. Results: Sex chromosome aneuploidies were identified in 67 cases (7.96%), with Turner syndrome (45, X) being the most frequent (23 cases, including six mosaics), followed by Klinefelter syndrome (18 cases), 47, XYY (14 cases), and trisomy X (12 cases). Among 19 NIPT-tested cases, 10 were true positives, 5 false positives, and 4 false negatives, including two mosaic Turner syndrome cases undetected by NIPT. Discordances were attributed to factors such as mosaicism and placental anomalies. Conclusions: Prenatal diagnosis of SCAs via invasive testing remains crucial due to NIPT’s limited sensitivity for mosaicism and false positives. Comprehensive genetic counseling is essential to navigate diagnostic uncertainties and optimize prenatal management and postnatal outcomes.

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