Implications of fetoplacental mosaicism on cell‐free <scp>DNA</scp> testing: a review of a common biological phenomenon

Grati, Francesca Romana

doi:10.1002/uog.15975

Cited by 48 publications

(75 citation statements)

References 94 publications

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“…Grati et al (2017) reported that the following risks of finding a mosaicism in CVS after a positive cfDNA result: 2% for T21, 4% for T18 and 22% for T13. While cfDNA testing is highly sensitive and specific, false positive results can occur and therefore positive results should be confirmed with invasive testing .…”

Section: Chromosomal Abnormalitiesmentioning

confidence: 99%

“…If the UPD involves imprinted gene regions, this can have clinical consequences. If CVS establishes CPM for chromosomes 6, 7, 11, 14, 15, 16 or 20, a diagnosis of UPD should be considered. In Table UPD syndromes associated with FGR are highlighted.…”

Section: Epigenetic Changesmentioning

confidence: 99%

“…In Table UPD syndromes associated with FGR are highlighted. The frequency of UPD in CPM of imprinted chromosomes is reported to be 2%. Furthermore, there is an increased risk of recessive disorders occurring due to homozygosity of some segments along the UPD homologues.…”

Section: Epigenetic Changesmentioning

confidence: 99%

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Genetic syndromes associated with isolated fetal growth restriction

2020

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Early onset fetal growth restriction (FGR) may be due to impaired placentation, environmental or toxic exposure, congenital infections or genetic abnormalities. Remarkable research, mainly based on retrospective series, has been published on the diverse genetic causes. Those have become more and more relevant with the improvement in the accuracy of the analysis techniques and the rising of breakthrough genomewide methods such as the whole genome sequencing. However, no publication has presented an integrated view of management of those fetuses with an early and severe affection. In this review, we explored to which extent genetic syndromes can cause FGR fetuses without structural defects. The most common chromosomal abnormalities (Triploidies and Trisomy 18), submicroscopic chromosomal anomalies (22q11.2 microduplication syndrome) and single gene disorders (often associated with mild ultrasound findings) related to early and severe FGR had been analysed. Finally, we addressed the impact of epigenetic marks on fetal growth, a matter of growing importance. At the end of this review, we should be able to provide an adequate counseling to parents in terms of diagnosis, prognosis and management of those pregnancies.

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Section: Chromosomal Abnormalitiesmentioning

confidence: 99%

Section: Epigenetic Changesmentioning

confidence: 99%

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Genetic syndromes associated with isolated fetal growth restriction

2020

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“…While 45,X can be present in 1-1.5% of recognizable pregnancies, about 99% of the cases do not survive gestation and only about 1% of the fetuses with this karyotype result in live births. The frequency of placental mosaicism for 45,X is quite high [15,16]. The phenotype of such mosaics (i.e., 45,X/46,XX, 45,X/46,XY, and 45,X/47,XXX) may vary considerably and does not necessarily have the syndrome [17].…”

Section: Comparison With Previous Studiesmentioning

confidence: 99%

Screening for Sex Chromosome Aneuploidy by Cell-Free DNA Testing: Patient Choice and Performance

Bevilacqua

Ordóñez²,

Hurtado

et al. 2017

Fetal Diagn Ther

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Objective: To study patient choice regarding testing for sex chromosome aneuploidy (SCA) and the performance of cell-free DNA (cfDNA) screening for SCA. Methods: Patient choice regarding screening for SCA and factors influencing this choice were evaluated in a single center. In a subsequent two-center study, cases that screened positive for SCA were analyzed to determine the positive predictive value (PPV) for each SCA. Results: In all, 1,957 (61.9%) of the 3,162 patients undergoing cfDNA testing opted for SCA screening. Regression analysis demonstrated that independent predictors of a patient's decision for SCA were earlier gestational age, spontaneous conception, and cfDNA chosen as a primary method of screening. A total of 161 cases screened positive for SCA and follow-up data were available for 118 (73.3%). Forty-six of the 61 cases of 45,X were false-positive results and 15 were concordant with the fetal karyotype (PPV = 24.6%). Seventeen of the 22 cases of 47,XXX were false positive and 5 concordant (PPV = 22.7%). Eleven of the 30 cases of 47,XXY were false positive and 19 concordant (PPV = 63.3%). All 5 cases of 47,XYY were correctly identified, thus yielding a PPV of 100%. Conclusion: More than half of the patients undergoing cfDNA aneuploidy screening also opted for SCA testing, but they were less likely to do so in the presence of an increased risk of trisomy. SCAs involving the X chromosome had a lower PPV than those involving the Y chromosome.

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“…After adequate pretest counseling, if the patient opts to have sex chromosome analysis performed and a discordant sex chromosome result occurs, a thorough maternal medical history review needs to be performed to help identify a possible cause. Important questions include the following: a review of the possibility of co-twin demise, history of or signs and symptoms of undiagnosed malignancies, and a history of organ transplantation from male or unknown sex donor (Grati, 2016;Gregg et al, 2013;Neofytou et al, 2018;Petersen et al, 2017;Reiss, Discenza, Foster, Dobson, & Wilkins-Haug, 2017;Smith et al, 2017;Society for Maternal-Fetal Medicine Publications Committee, 2015;Wang et al, 2014). If no potential etiology is identified in the maternal history, it is then important to contact the laboratory where the test was performed to confirm the original sample and patient information, and to either retest the sample or send a new sample to rule out laboratory error or contamination.…”

Section: Management/counselingmentioning

confidence: 99%

Fetal sex discordance between noninvasive prenatal screening results and sonography: A single institution's experience and review of the literature

Sylvester-Armstrong

Rasmussen

Shoraka

et al. 2019

Birth Defects Research

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Background With the increasing availability of noninvasive prenatal screening (NIPS) and high‐resolution ultrasound, more cases of sex discordance are being identified in routine clinical practice. This can be a source of much concern for families and clinicians. Knowledge about the limitations of NIPS and reasons for discordant results are critical for counseling parents. Aims Here, we present three cases from a single tertiary care referral center. We also review the literature to address potential limitations of NIPS in correctly identifying fetal sex chromosomes. Materials and Methods After Institutional Review Board approval, cases of discordant fetal sex were identified using ICD‐9 and ICD‐10 codes. In addition, departmental counseling database and cytogenetics laboratory logbooks were reviewed. Results In our first case, a 37‐year‐old G4 P2012 underwent NIPS at 11 weeks gestation and Monosomy X (associated with Turner syndrome) was identified. Morphological sonographic assessment at 20 weeks gestation was consistent with a female fetus following an amniocentesis at 16 weeks that revealed normal 46, XX karyotype. During the third trimester, the patient was diagnosed with Stage IV invasive ductal carcinoma of the breast. Postnatal follow‐up of the neonate was consistent with a phenotypic female. In the second case, a 22‐year‐old G2 P1001 obese female underwent NIPS at 14 weeks gestation and normal 46, XY karyotype was identified. Morphological sonographic assessment at 20 weeks was not consistent with a male fetus. The patient declined invasive testing. Postnatally, the karyotype was 46, XX and the neonate was phenotypically female. The reason for the discordant results was not identified. In the third case, a 25‐year‐old G1 P0 obese female underwent NIPS at 13 weeks gestation and normal 46, XY karyotype was identified. Morphological sonographic assessment at 20 weeks was indeterminate; however, follow‐up at 24 weeks was consistent with a female fetus. The patient declined invasive prenatal testing. Postnatally, the karyotype was 46, XX, and the neonate was phenotypically female with uterus present on ultrasound. The reason for the discordant results was not identified. Discussion Our cases demonstrate possible limitations of NIPS in correctly identifying sex chromosomes. Conclusions Providers and patients need to be aware of these limitations, and invasive diagnostic prenatal testing should be offered in cases of discordance between NIPS and sonographic sex assessment.

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Implications of fetoplacental mosaicism on cell‐free DNA testing: a review of a common biological phenomenon

Cited by 48 publications

References 94 publications

Genetic syndromes associated with isolated fetal growth restriction

Genetic syndromes associated with isolated fetal growth restriction

Screening for Sex Chromosome Aneuploidy by Cell-Free DNA Testing: Patient Choice and Performance

Fetal sex discordance between noninvasive prenatal screening results and sonography: A single institution's experience and review of the literature

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