Noninvasive prenatal screening (NIPS) for fetal chromosome abnormalities in a general-risk population: An evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG)

Dungan, J.S.; Klugman, Susan; Darilek, Sandra; Malinowski, Jennifer; Akkari, Yassmine; Monaghan, Kristin G.; Erwin, Angelika; Best, Robert G.

doi:10.1016/j.gim.2022.11.004

Cited by 94 publications

(102 citation statements)

References 53 publications

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“…Screening for selected microdeletions, including the 22q11.2 microdeletion, has been available since 2015. The American College of Medical Genetics and Genomics has recently suggested that NIPS for 22q11.2DS be offered to all patients as a conditional recommendation, based on moderate certainty of evidence [25].…”

Section: Noninvasive Prenatal Screening (Nips) For 22q112 Microdeletionsmentioning

confidence: 99%

Prenatal Screening and Diagnostic Considerations for 22q11.2 Microdeletions

Blagowidow

Nowakowska²,

Schindewolf

et al. 2023

Genes

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Diagnosis of a chromosome 22q11.2 microdeletion and its associated deletion syndrome (22q11.2DS) is optimally made early. We reviewed the available literature to provide contemporary guidance and recommendations related to the prenatal period. Indications for prenatal diagnostic testing include a parent or child with the 22q11.2 microdeletion or suggestive prenatal screening results. Definitive diagnosis by genetic testing of chorionic villi or amniocytes using a chromosomal microarray will detect clinically relevant microdeletions. Screening options include noninvasive prenatal screening (NIPS) and imaging. The potential benefits and limitations of each screening method should be clearly conveyed. NIPS, a genetic option available from 10 weeks gestational age, has a 70–83% detection rate and a 40–50% PPV for most associated 22q11.2 microdeletions. Prenatal imaging, usually by ultrasound, can detect several physical features associated with 22q11.2DS. Findings vary, related to detection methods, gestational age, and relative specificity. Conotruncal cardiac anomalies are more strongly associated than skeletal, urinary tract, or other congenital anomalies such as thymic hypoplasia or cavum septi pellucidi dilatation. Among others, intrauterine growth restriction and polyhydramnios are additional associated, prenatally detectable signs. Preconception genetic counselling should be offered to males and females with 22q11.2DS, as there is a 50% risk of transmission in each pregnancy. A previous history of a de novo 22q11.2 microdeletion conveys a low risk of recurrence. Prenatal genetic counselling includes an offer of screening or diagnostic testing and discussion of results. The goal is to facilitate optimal perinatal care.

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Section: Noninvasive Prenatal Screening (Nips) For 22q112 Microdeletionsmentioning

confidence: 99%

Prenatal Screening and Diagnostic Considerations for 22q11.2 Microdeletions

Blagowidow

Nowakowska²,

Schindewolf

et al. 2023

Genes

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“…Ultimately, this study shows that MPS-based cfDNA screening for 22q11.2DS can be an effective screening tool, may distinguish maternal from fetal events, and can be used to estimate the size and predicted location of the deletion. Positive screening results should be confirmed by diagnostic testing with microarray analysis, and no irreversible management decisions should be made on the basis of screening results alone, consistent with professional society recommendations (American College of Obstetricians and Gynecologists' Committee on Practice Bulletins-Obstetrics et al, 2020;Dungan et al, 2022). Furthermore, counseling following a screen-positive result should include a discussion of the variability in clinical features, although there is some genotype-phenotype correlation noted (McDonald-McGinn et al, 2015).…”

Section: Discussionmentioning

confidence: 94%

“…although cardiac anomalies, oral clefting, polyhydramnios, renal abnormalities, and skeletal abnormalities are among the findings that may be identified during routine ultrasonography (McDonald-McGinn et al, 1999). CfDNA screening for 22q11.2DS became clinically available in 2013 (Helgeson et al, 2015), yet most professional societies have yet to support routine screening for this condition during pregnancy due to a lack of clinical data and the perception of a reduced positive predictive value (PPV) associated with a positive screening result, ranging from 18% to greater than 97% (Helgeson et al, 2015;Gross et al, 2016;Martin et al, 2018; American College of Obstetricians and Gynecologists' Committee on Practice Bulletins-Obstetrics et al, 2020;Bevilacqua et al, 2021;Soster et al, 2021;Dar et al, 2022;Dungan et al, 2022;Rose et al, 2022). Recently, the American College of Medical Genetics (ACMG) "suggests that screening for 22q11.2 deletion syndrome be offered to all patients" as a conditional recommendation based on moderate certainty of evidence (Dungan et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

“…CfDNA screening for 22q11.2DS became clinically available in 2013 (Helgeson et al, 2015), yet most professional societies have yet to support routine screening for this condition during pregnancy due to a lack of clinical data and the perception of a reduced positive predictive value (PPV) associated with a positive screening result, ranging from 18% to greater than 97% (Helgeson et al, 2015;Gross et al, 2016;Martin et al, 2018; American College of Obstetricians and Gynecologists' Committee on Practice Bulletins-Obstetrics et al, 2020;Bevilacqua et al, 2021;Soster et al, 2021;Dar et al, 2022;Dungan et al, 2022;Rose et al, 2022). Recently, the American College of Medical Genetics (ACMG) "suggests that screening for 22q11.2 deletion syndrome be offered to all patients" as a conditional recommendation based on moderate certainty of evidence (Dungan et al, 2022). Prenatal identification of 22q11.2DS allows parents to make informed reproductive choices and may have benefit for both perinatal management and maternal health, and may help to avoid a potential "diagnostic odyssey" for an affected child (McDonald-Mcginn et al, 2001;Bassett et al, 2011;Cheung et al, 2014;Fung et al, 2015;McDonald-McGinn et al, 2015; Van et al, 2016;McDonald-McGinn, 2018).…”

Section: Introductionmentioning

confidence: 99%

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Positive cfDNA screening results for 22q11.2 deletion syndrome—Clinical and laboratory considerations

et al. 2023

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Introduction: Non-invasive prenatal screening (NIPS) via cell-free DNA (cfDNA) screens for fetal chromosome disorders using maternal plasma, including 22q11.2 deletion syndrome (22q11.2DS). While it is the commonest microdeletion syndrome and has potential implications for perinatal management, prenatal screening for 22q11.2DS carries some inherent technical, biological, and counseling challenges, including varying deletion sizes/locations, maternal 22q11.2 deletions, confirmatory test choice, and variable phenotype.Materials and methods: This study addresses these considerations utilizing a retrospective cohort of 307 samples with screen-positive 22q11.2 NIPS results on a massively parallel sequencing (MPS) platform.Results: Approximately half of the cases reported ultrasound findings at some point during pregnancy. In 63.2% of cases with diagnostic testing, observed positive predictive values were 90.7%–99.4%. cfDNA identified deletions ranging from <1 Mb to 3.55 Mb, with significant differences in confirmed fetal versus maternal deletion sizes; estimated cfDNA deletion size was highly concordant with microarray findings. Mosaicism ratio proved useful in predicting the origin of a deletion (fetal versus maternal). Prediction of deletion size, location, and origin may help guide confirmatory testing.Discussion: The data shows that MPS-based NIPS can screen for 22q11.2DS with a high PPV, and that collaboration between the laboratory and clinicians allows consideration of additional metrics that may guide diagnostic testing and subsequent management.

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“…While there is variation in test performance depending on the specific SCA involved, NIPT for the two most common SCAs, 45X and 47, XYY is now recognized to have high sensitivity and specificity. Indeed, the American College of Medical Genetics and Genomics has recently updated their practice guideline on prenatal screening to strongly recommend that SCA screening with NIPT be offered to all women with singleton pregnancies 2 …”

mentioning

confidence: 99%

Prenatal screening and diagnosis of sex chromosome conditions: The new normal?

Hui

Langlois

2023

Prenatal Diagnosis

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In this era of noninvasive prenatal testing (NIPT) with maternal plasma cell-free DNA (cf-DNA), prenatal screening and diagnosis of sex chromosome aneuploidy (SCAs) is increasingly part of our clinical practice. This development, facilitated by the technological advances in NIPT, has been enthusiastically embraced in many settings, though not universally. In this special topic issue of Prenatal Diagnosis, we address the many clinical, ethical, and technical aspects of prenatal testing for sex chromosome conditions.How well does NIPT perform for the SCAs? In this issue, Shear at al. have conducted a systematic review and meta-analysis of cfDNA testing for fetal SCA, which provides readers with updated performance metrics that will be useful for counseling and clinical practice guidelines. 1 While there is variation in test performance depending on the specific SCA involved, NIPT for the two most common SCAs, 45X and 47, XYY is now recognized to have high sensitivity and specificity. Indeed, the American College of Medical Genetics and Genomics has recently updated their practice guideline on prenatal screening to strongly recommend that SCA screening with NIPT be offered to all women with singleton pregnancies. 2 The popularity of SCA screening with NIPT is already widespread, as shown by Steffensen et al. who conducted a global survey of current practices across Europe, Asia, Australia, and the USA. 3 The impact of SCA screening is already evident in Australia, where a population-based study has demonstrated a significant increase in the prenatal detection of SCAs, most notably 47,XXY, since the availability of NIPT. 4 In concert with these trends, we continue to integrate information about fetal sex chromosomes with prenatal ultrasound findings, including the assessment of atypical genitalia, 5 management of suspected X chromosome variants and monosomy X, 6 and expanding knowledge about the prenatal phenotype of 45,X 7 and 47,XXY. 8 Furthermore, Scarff et al.

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Noninvasive prenatal screening (NIPS) for fetal chromosome abnormalities in a general-risk population: An evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG)

Cited by 94 publications

References 53 publications

Prenatal Screening and Diagnostic Considerations for 22q11.2 Microdeletions

Prenatal Screening and Diagnostic Considerations for 22q11.2 Microdeletions

Positive cfDNA screening results for 22q11.2 deletion syndrome—Clinical and laboratory considerations

Prenatal screening and diagnosis of sex chromosome conditions: The new normal?

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