Non-Invasive Screening Tools for Down's Syndrome: A Review.

Kelly A Sillence,Llinos A Roberts,Neil D Avent,Timothy G Overton,Tracey E Madgett

doi:10.3390/diagnostics3020291

Abstract

Down’s syndrome (DS) is the most common genetic cause of developmental delay with an incidence of 1 in 800 live births, and is the predominant reason why women choose to undergo invasive prenatal diagnosis. However, as invasive tests are associated with around a 1% risk of miscarriage new non-invasive tests have been long sought after. Recently, the most promising approach for non-invasive prenatal diagnosis (NIPD) has been provided by the introduction of next generation sequencing (NGS) technologies. The clinical application of NIPD for DS detection is not yet applicable, as large scale validation studies in low-risk pregnancies need to be completed. Currently, prenatal screening is still the first line test for the detection of fetal aneuploidy. Screening cannot diagnose DS, but developing a more advanced screening program can help to improve detection rates, and therefore reduce the number of women offered invasive tests. This article describes how the prenatal screening program has developed since the introduction of maternal age as the original “screening” test, and subsequently discusses recent advances in detecting new screening markers with reference to both proteomic and bioinformatic techniques.

Highlights

Down syndrome (DS) is the most common chromosomal aneuploidy and is the leading genetic cause of developmental delay
This review demonstrates how screening for the detection of Down‘s syndrome (DS) has improved since the early 1980s when maternal age was the only ―tool‖ available
A recent trial conducted within the UK to assess the performance of non-invasive prenatal testing (NIPT) for fetal trisomy in a routinely screened first-trimester population identified a detection rate (DR) of >99% and a false positive rate of 0.1%

Summary

Introduction

Down syndrome (DS) is the most common chromosomal aneuploidy and is the leading genetic cause of developmental delay. The overall incidence of DS is around 1 in 800 live births [1,2], but the risk of fetal trisomy is directly related to maternal age, increasing gradually up to age 33 and subsequently increasing exponentially (Figure 1). Women in their late 40s have an incidence rate of around 1 in 32 live births [3]. In the UK the National Down‘s Syndrome Cytogenetic Register (NDSCR) indicated that without improved screening tools between 1989 and 2008, the continuous rise in maternal age would have caused a 48% increase in live births with DS [3]. There are clear ethical issues surrounding prenatal screening, with the majority of women terminating affected pregnancies, the evidence provided clearly illustrates the effectiveness of screening for DS

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Results

Conclusion