Follow-up of multiple aneuploidies and single monosomies detected by noninvasive prenatal testing: implications for management and counseling

Abstract

ObjectivesTo determine the underlying biological basis for noninvasive prenatal testing (NIPT) results of multiple aneuploidies or autosomal monosomies.MethodsRetrospective analysis of 113,415 tests to determine the study cohort, consisting of 138 (0.12%) cases reported as a single autosomal monosomy (n = 65), single trisomy with a sex chromosome aneuploidy (n = 36), or with multiple aneuploidies (n = 37). Clinical outcome information was reviewed and stratified into eight categories according to whether the karyotype or sonographic information agreed or disagreed with sequencing results.ResultsOf 67 cases with fetal or neonatal karyotypes available, 16 (24%) were partially or fully concordant with the NIPT result, 4 (6%) had aneuploidy on a reference chromosome, and 47 (70%) had normal fetal chromosomes, in which 5/47 had maternal malignancies reported. One case of maternal mosaic trisomy 8 was also detected. Of cases with no fetal karyotype information, ten had an abnormal clinical outcome, one was a normal live birth, and one reported maternal malignancy.ConclusionsNoninvasive prenatal test results of autosomal monosomy or multiple aneuploidies are rare but have a diversity of underlying biologic causes. Some reflect the fetal karyotype; some reflect the presence of other maternal or fetal chromosome abnormalities, and a small number are linked to maternal disease. © 2016 Illumina. Prenatal Diagnosis published by John Wiley & Sons, Ltd.

Maternal chromosome Xp deletion identified by prenatal cell‐free DNA screening

“…Prenatal cfDNA screening has more recently been validated to detect fetal copy number variations (CNVs), depending upon factors such as CNV size and sequencing depth. Emerging evidence indicates that prenatal cfDNA screening can also potentially detect maternal CNVs with accuracy similar to that of CMA depending upon sequencing read depth and use of large amounts of short reads for favorable resolution, and possibly confirm a related diagnosis of suspicion such as triple X syndrome, malignancy, or fibroids, all of which can be suspected clinically . Our findings underscore the potential clinical significance of maternal CNVs detected incidentally during cfDNA screening; in this case, such screening identified a chromosome Xp deletion, resulting in variant Turner syndrome, as the likely cause of the patient's previous incident of infertility.…”

Biological explanations for discordant noninvasive prenatal test results: Preliminary data and lessons learned

“…Another major reason for a discordant cfDNA result is that the pregnant woman herself has a partial or mosaic autosomal or sex chromosome aneuploidy . Sex chromosome aneuploidies have a mild clinical phenotype and may be clinically unrecognized in the pregnant woman .…”

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“…However, it may also lead to undue anxiety, especially when no cancer is found in follow‐up investigations. This number may be as high as 53%, as seen in the follow‐up study by Snyder and colleagues of single monosomies and multiple aneuploidies detected by NIPT …”