Abstract
Microarrays have replaced conventional karyotyping as a first-tier test for unbalanced chromosome anomalies in postnatal cytogenetics mainly due to their unprecedented resolution facilitating the detection of submicroscopic copy number changes at a rate of 10–20% depending on indication for testing. A number of studies have addressed the performance of microarrays for chromosome analyses in high risk pregnancies due to abnormal ultrasound findings and reported an excess detection rate between 5% and 10%. In low risk pregnancies, clear pathogenic copy number changes at the submicroscopic level were encountered in 1% or less. Variants of unclear clinical significance, unsolicited findings, and copy number changes with variable phenotypic consequences are the main issues of concern in the prenatal setting posing difficult management questions. The benefit of microarray testing may be limited in pregnancies with only moderately increased risks (advanced maternal age, positive first trimester test). It is suggested to not change the current policy of microarray application in prenatal diagnosis until more data on the clinical significance of copy number changes are available.
Highlights
Microarrays detecting copy number changes in genomic DNA [1] have replaced conventional microscopic chromosome analyses in the routine diagnostic work-up of children and adults with suspected unbalanced chromosome anomalies during recent years [2,3]
These include the common observation of copy number variation (CNV) with unknown clinical significance (VOUS) being obviously more difficult to manage in the sensitive prenatal setting as well as the fact that the majority of all unbalanced chromosome findings in prenatal diagnosis concern common trisomies or other anomalies perfectly amenable to the conventional diagnostic approach or by the recently introduced non-invasive prenatal testing (NIPT) on a maternal blood sample [11]
VOUS were seen in 4.2% of all cases, a rate dropping to 0.4% if only de novo findings were included. 71% of the aberrations were not detectable by conventional karyotyping
Summary
Microarrays detecting copy number changes in genomic DNA [1] have replaced conventional microscopic chromosome analyses in the routine diagnostic work-up of children and adults with suspected unbalanced chromosome anomalies during recent years [2,3]. The use of microarrays in this setting has been met with caution for various reasons [9,10] These include the common observation of copy number variation (CNV) with unknown clinical significance (VOUS) being obviously more difficult to manage in the sensitive prenatal setting as well as the fact that the majority of all unbalanced chromosome findings in prenatal diagnosis concern common trisomies or other anomalies perfectly amenable to the conventional diagnostic approach or by the recently introduced non-invasive prenatal testing (NIPT) on a maternal blood sample [11]. This contribution will review the current clinical application of microarrays in prenatal cytogenetics and discuss aspects relevant to its formal implementation as an addition to or as a replacement of alternative diagnostic options
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