Cell-free DNA screening positive for monosomy X: clinical evaluation and management of suspected maternal or fetal Turner syndrome

Dowlut‐McElroy, Tazim; Davis, Shanlee; Howell, Susan; Gutmark‐Little, Iris; Bamba, Vaneeta; Prakash, Siddharth K.; Patel, Suhag; Fadoju, Doris; Vijayakanthi, Nandini; Haag, Mary M.; Hennerich, Ms Deborrah; Dugoff, Lorraine; Shankar, Roopa Kanakatti

doi:10.1016/j.ajog.2022.07.004

Cited by 7 publications

(5 citation statements)

References 86 publications

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“…Because the constitutional karyotype may differ from that obtained from chorionic villi or amniocytes, in particular for mosaic sex chromosome abnormalities, we are making efforts to raise awareness about the benefits of postnatal karyotype confirmation. 6,71,72 We know that CPM, which is reported in 2% of all CVS and is higher for monosomy X in the absence of fetal anomalies, is an important source of false positive results in cfDNA-based screening for SCA, particularly for monosomy X. 40,46 Unfortunately, because this was a retrospective survey, we do not have genetic information from placental biopsies for all cases and can therefore not comment on the rate of CPM as a source of FP results in our study.…”

Section: Discussionmentioning

confidence: 99%

“…Confirmation of the prenatal karyotype after birth was rarely reported, which may reflect practice patterns in Germany. Because the constitutional karyotype may differ from that obtained from chorionic villi or amniocytes, in particular for mosaic sex chromosome abnormalities, we are making efforts to raise awareness about the benefits of postnatal karyotype confirmation 6,71,72 . We know that CPM, which is reported in 2% of all CVS and is higher for monosomy X in the absence of fetal anomalies, is an important source of false positive results in cfDNA‐based screening for SCA, particularly for monosomy X 40,46 .…”

Section: Discussionmentioning

confidence: 99%

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Multicenter clinical experience with non‐invasive cell‐free DNA screening for monosomy X and related X‐chromosome variants

et al. 2023

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Objective We aimed to investigate how the presence of fetal anomalies and different X chromosome variants influences Cell‐free DNA (cfDNA) screening results for monosomy X. Methods From a multicenter retrospective survey on 673 pregnancies with prenatally suspected or confirmed Turner syndrome, we analyzed the subgroup for which prenatal cfDNA screening and karyotype results were available. A cfDNA screening result was defined as true positive (TP) when confirmatory testing showed 45,X or an X‐chromosome variant. Results We had cfDNA results, karyotype, and phenotype data for 55 pregnancies. cfDNA results were high risk for monosomy X in 48/55, of which 23 were TP and 25 were false positive (FP). 32/48 high‐risk cfDNA cases did not show fetal anomalies. Of these, 7 were TP. All were X‐chromosome variants. All 16 fetuses with high‐risk cfDNA result and ultrasound anomalies were TP. Of fetuses with abnormalities, those with 45,X more often had fetal hydrops/cystic hygroma, whereas those with “variant” karyotypes had different anomalies. Conclusion Both, 45,X or X‐chromosome variants can be detected after a high‐risk cfDNA result for monosomy X. When there are fetal anomalies, the result is more likely a TP. In the absence of fetal anomalies, it is most often an FP or X‐chromosome variant.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Multicenter clinical experience with non‐invasive cell‐free DNA screening for monosomy X and related X‐chromosome variants

et al. 2023

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“…An algorithm for a pathway for testing following a cfDNA high risk for Turner syndrome has been recently published and is similar to these recommendations. 32 In another series of 975 prenatally diagnosed cases of Turner syndrome, 84% were found to have sonographic abnormalities, most commonly increased NT or cystic hygroma (91%). 33 Other studies have estimated similar detection rates.…”

Section: Monosomy Xmentioning

confidence: 98%

“…If the testing is normal or the patient declines invasive testing, then maternal testing can be considered. An algorithm for a pathway for testing following a cfDNA high risk for Turner syndrome has been recently published and is similar to these recommendations 32 …”

Section: Monosomy Xmentioning

confidence: 99%

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Chorionic Villous Testing Versus Amniocentesis After Abnormal Noninvasive Prenatal Testing

ROGERS,

MARDY

2023

Clinical Obstetrics &Amp; Gynecology

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In the setting of a normal first-trimester ultrasound, an amniocentesis may be a better option than chorionic villous sampling for invasive diagnostic testing after a cell-free DNA high risk for trisomy 13, given the high rates of confined placental mosaicism. In unaffected fetuses, other evaluations should be considered depending on the cell-free DNA results, including maternal karyotyping for monosomy X, uniparental disomy testing for chromosomes with imprinted genes, serial growth scans for trisomy 16, and a workup for maternal malignancy for multiple aneuploidies or autosomal monosomy.

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Prevalence, diagnostic features, and medical outcomes of females with Turner syndrome with a trisomy X cell line (45,X/47,XXX): Results from the InsighTS Registry

Klamut,

Bothwell,

Carl

et al. 2024

American J of Med Genetics Pt A

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Turner syndrome (TS) is defined by partial or complete absence of a sex chromosome. Little is known about the phenotype of individuals with TS mosaic with trisomy X (45,X/47,XXX or 45,X/46,XX/47,XXX) (~3% of TS). We compared the diagnostic, perinatal, medical, and neurodevelopmental comorbidities of mosaic 45,X/47,XXX (n = 35, 9.4%) with nonmosaic 45,X (n = 142) and mosaic 45,X/46,XX (n = 66). Females with 45,X/47,XXX had fewer neonatal concerns and lower prevalence of several TS‐related diagnoses compared with 45,X; however the prevalence of neurodevelopmental and psychiatric diagnoses were not different. Compared to females with 45,X/46,XX, the 45,X/47,XXX group was significantly more likely to have structural renal anomalies (18% vs. 3%; p = 0.03). They were twice as likely to have congenital heart disease (32% vs. 15%, p = 0.08) and less likely to experience spontaneous menarche (46% vs. 75% of those over age 10, p = 0.06), although not statistically significant. Congenital anomalies, hypertension, and hearing loss were primarily attributable to a higher proportion of 45,X cells, while preserved ovarian function was most associated with a higher proportion of 46,XX cells. In this large TS cohort, 45,X/47,XXX was more common than previously reported, individuals were phenotypically less affected than those with 45,X, but did have trends for several more TS‐related diagnoses than individuals with 45,X/46,XX.

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Cell-free DNA screening positive for monosomy X: clinical evaluation and management of suspected maternal or fetal Turner syndrome

Cited by 7 publications

References 86 publications

Multicenter clinical experience with non‐invasive cell‐free DNA screening for monosomy X and related X‐chromosome variants

Multicenter clinical experience with non‐invasive cell‐free DNA screening for monosomy X and related X‐chromosome variants

Chorionic Villous Testing Versus Amniocentesis After Abnormal Noninvasive Prenatal Testing

Prevalence, diagnostic features, and medical outcomes of females with Turner syndrome with a trisomy X cell line (45,X/47,XXX): Results from the InsighTS Registry

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