Perinatal Tıp Vakfı Tarafından Önerilen Test

PVDR-HERO2

Fetal DNA Testi

Fetal kromozom anomalileri için geliştirilmiş olan bir non invaziv prenatal tarama testidir (NIPT). Test, anne kanındaki plasenta kaynaklı serbest fetal DNA’nın değerlendirilebilmesi için gelişmiş biyoinformatik teknolojiyi kullanır.

Anne kanındaki fetal ve maternal DNA arasındaki ayırımı yaparak size ve hastanıza bebek hakkında hayati bilgiler bilgiler verebilir. Kromozomal anöploidiler ve mikrodelesyonları içeren kapsamlı panel sayesinde, 9-10. gebelik haftası gibi erken bir dönemde herhangi bir tarama testindeki en doğru sonuçları elde etmenizi sağlayarak hastalarınızın gebeliğini doğru bir şekilde yönetmenize yardımcı olur.

Niçin Fetal DNA Testi?

Sizin ve hastalarınızın, sık gözlenen kromozomal bozuklukların panel olarak incelendiği ve en yüksek doğruluğa sahip olan bir prenatal tarama testinin kullanılması artık mümkün hale gelmiştir. En gelişmiş biyoinformatik teknoloji ile güçlendirilmiş olan fetal DNA testi, yayınlanmış bilimsel çalışmalarda en yüksek kombine doğruluğa sahip olup kromozom 21, 18, 13, X ve Y anöploidileri ve triploidi ile mikrodelesyonlar için kişiye özel risk skorlaması yapılabilmesini sağlayan bir testtir.

Avantajları:

VAST Vanishing Twin (kaybolan ikiz): Kaybolan ikize ait maternal dolaşımdaki DNA’nin varlığını sadece Panorama ayırt edebilmektedir. Kaybolan ikize ait DNA varlığı diğer NIPT yöntemleri ile saptanamayabilir ve bu nedenle de yanlış pozitif ve yanlış negatif test sonuçları ile karşılaşma ihtimali artabilir.

Maternal genotip Analizi: Gebeliklerdeki sonuçların daha net olması açısından, fetal genotipe ilave olarak maternal genotipin de belirlenmesi sadece Panorama testinde yapılmaktadır.

Seks kromozomlarının değerlendirilmesi: Panorama; 47,XXX, 47,XXY, 47,XYY gibi cinsiyet kromozom anomalilerini yüksek doğrulukta tanımlamaktadır.

Triploidi: Triploidi risk değerlendirmesi sadece Panorama testi ile mümkündür. Özellikle, USG bulgularının triplodiye işaret ettiği gebeliklerde ve önceki gebeliklerde saptanmış bir triploidi öyküsü nedeniyle tekrarlama riski açısından endişeli olan ailelerde faydalıdır. Panorama testi, düşük fetal DNA oranlarında dahi yüksek sensitiviteye sahiptir.

Fetal DNA Testi ile Neler Taranabilir?

Anöploidiler
•Trizomi 21 (Down sendromu)
•Trizomi 18 (Edwards sendromu)
•Trizomi 13 (Patau sendromu)
•Monozomi X (Turner sendromu)
•Klinefelter sendromu
•Triple X sendromu
•XYY sendromu
•Triploidi
•Vanishing twin

Mikrodelesyonlar
•DiGeorge (22q11.2) sendromu
•1p36 delesyon sendromu
•Prader Willi sendromu
•Angelman sendromu
•Cri-du-chat sendromu

Panorama Testi Nasıl Çalışır?

how it works

Clinical results chart new(1)

Results: 1,194 samples passed quality control thresholds: 1,186 were called at all five chromosomes; 8 were called at four chromosomes; 192 samples were of unknown gender. We observed two false positives (45,X and T18), and one false negative (45,X) in this cohort, for a total of 5,767/5,770 correct calls. Samples that failed to meet this threshold (5.8% for samples ≥10 weeks of gestation [n=1,141]; 10.7% for 9 weeks GA [n=56]) were typically of poor DNA quality. Correct identification of low quality samples enables redraw and retesting of the patient rather than reporting a low quality call with an increased risk of false negatives/positives. Gender is defined by presence or absence of the Y chromosome.1,2 Five samples of diandric triploidy identified as ‘triploidy or twins’; three samples of digynic triploidy identified as having abnormally low fetal fraction (<0.5%ile), correctly indicating triploidy.1,3 This methodology identified Klinefelter (47,XXY) and 47,XYY in a previous dataset with 100% sensitivity (4/4 and 1/1, respectively), and 100% specificity (332/332).4,5 This sample cohort was not analyzed for sex chromosome trisomies. Four mosaic samples were excluded from this cohort.

1 Nicolaides KH, Syngelaki A, Gil M, Atanasova V, Markova D. Prenat Diagn 2013;33:1-5.

2 Levy B; European Society of Human Reproduction and Embryology Meeting, July 7-10, 2013 in London, UK.

3 Nicolaides, KH; Fetal Medicine Foundation Meeting, June 23-27, 2013 in Marbella, Spain.

4 Zimmermann B, Hill M, Gemelos G, et al. Prenat Diagn. 2012;32:1233-1241.

5 Samango-Sprouse C, Banjevic M, Ryan A, et al. Prenat Diagn 2013;33:1-7.

6 Presented at ASHG (November 2012) 7 Zimmerman et al. Prenat Diag. 2012 

Clinical experience and follow-up with large scale single-nucleotide polymorphismebased noninvasive prenatal aneuploidy testing.

By Pe’er Dar, MD et al. Panorama’s clinical performance was consistent with performance in validation studies.

  • >90% positive predictive value (PPV) for trisomies 21 and 18; 83% PPV overall for trisomies 21, 18 and 13, and Monosomy X.
  • Similar PPVs in high- and low-risk patients.
  • No reports of incorrect fetal sex from the >20,000 patients who received low risk NIPT reports.

Click Here to View

Detection of triploid, molar, and vanishing-twin pregnancies by a single-nucleotide polymorphism-based non-invasive prenatal test

By Kirsten Curnow, Ph.D. Panorama successfully identified vanished twin, previously unrecognized twin, and triploid pregnancies. The ability of the SNP-based method to identify additional fetal haplotypes is expected to result in fewer false positive calls and prevent incorrect fetal sex calls. Click Here to View

Single-Nucleotide Polymorphism–Based Noninvasive Prenatal Screening in a High-Risk and Low-Risk Cohort

Eugene Pergament, MD, PhD Sensitivity and specificity did not differ in low-risk and high-risk populations. Sensitivity was 100% for trisomy 21 (58/58, confidence interval [CI] 93.8–100%), trisomy 13 (12/12, CI 73.5– 100%), and fetal sex (358/358 female, CI 99.0–100%; 418/ 418 male, CI 99.1–100%), 96.0% for trisomy 18 (24/25, CI 79.7–99.9%), and 90% for monosomy X (9/10, CI 55.5– 99.8%). Specificity for trisomies 21 and 13 was 100% (905/905, CI 99.6–100%; and 953/953, CI 99.6–100%, respectively) and for trisomy 18 and monosomy X was 99.9% (938/939, CI 99.4–100%; and 953/954, CI 99.4–100%, respectively). Click here to view

Published articles that relate to Panorama™

  • The impact of maternal fetal plasma DNA fetal fraction on next generation sequencing test for common fetal aneuploidies.                                                                               Canmick JA,  Palomaki GE, Kloza EM, Lambert-Messerlian GM, Haddow JE Prenat Diag. 2013 July: 33(7), 667-74.  DOI: 10.1002/pd.4126
  • Prenatal detection of fetal triploidy from cell-free DNA testing in maternal blood. Nicolaides KH, Syngelaki A, del Mar Gil M, Soledad Quezada M, Zinevich Y. Fetal Diagn Ther 2013;doi:10.1159/000355655 *Externally-blinded, 20K protocol, NATUS, first study specifically aimed at triploidy detection.
  • Validation of targeted sequencing of single-nucleotide polymorphisms for non-invasive prenatal detection of aneuploidy of chromosomes 13, 18, 21, X, and Y. Nicolaides KH, Syngelaki A, Gil M, Atanasova V, Markova D. Prenat Diagn2013;33:1-5. *Externally-blinded, first published account of cfDNA-based triploidy detection, 20K protocol, NATUS.
  • SNP-based non-invasive prenatal testing detects sex chromosome aneuploidies with high accuracy. Samango-Sprouse C, Banjevic M, Ryan A, et al. Prenat Diagn 2013; 33;643-9. *Sex chromosome aneuploidy detection, 20K protocol, NATUS.
  • Noninvasive prenatal aneuploidy testing of chromosomes 13, 18, 21, X, and Y, using targeted sequencing of polymorphic loci. Zimmermann B, Hill M, Gemelos G, et al. Prenat Diagn 2012; 32:1233-41. *Proof-of-concept, 11K protocol, Parental Support.
  • Non-invasive prenatal testing for whole chromosome abnormalities. Demko ZP, Zimmermann B, Rabinowitz M. J. Lab. Med. 2012;36:263-267. *Review.
  • Cell-free fetal DNA and maternal serum analytes for monitoring embryonic and fetal status. Simpson JL. Fertil Steril 2013;99:1124–34. *Review.
  • Non-invasive prenatal aneuploidy testing: technologies and clinical implications. Levy BL, Norwitz E. Med Lab Obs 2013. *Review.

Sonuçların ve gebelik döneminde gerekli olabilecek planlamaların anlaşılabilmesi konusunda size yardımcı olabilmek için bireysel risk skorlamasını içeren geniş ve kapsamlı bir rapor sunulmaktadır.

Yüksek risk – Trizomi 18

Trizomi-18

Yüksek risk – DiGeorge sendromu

DiGeorge

Düşük risk raporu

Genis

Onam Formu

Trizomi 21,18,13 ve Monozomi X, Triploidi ve ek olarak mikrodelesyon sendromları (22q11.2 deletion syndrome, 1p36 deletion syndrome, Cri-du-chat syndrome, Angelman syndrome, and Prader-Willi syndrome) için Fetal DNA Tarama Testi yaptırmak isteyenlerin aşağıda belirtilen hususları dikkatli olarak okuyup anladıktan sonra imzalamaları gereken bir izin belgesidir.

Prenatal Testing Algorithm Consent Form (pdf 156.08 KB)

This consent form was created to help providers discuss different prenatal testing options for anueploidy and microdeletions with their patients.  There is a patient signature line for acknowledgment of receipt and understanding of the information.


 

KAYNAKLAR

Patient Guide to Results (pdf 441.78 KB)

Panorama is a non-invasive prenatal screening test (NIPT) that uses advanced DNA technology to provide pregnant women with a more accurate idea of their risks for having a baby with certain types of genetic conditions.  Sometimes, a patient’s result report may come back as “unable to report.”  Attached are the reasons as to why this might happen.

Microdeletions Insert (pdf 1001.01 KB)

Panorama™ now screens for the most common and severe microdeletion syndromes, in addition to its basic screen for T21, T18, T13, triploidy, and sex chromosome abnormalities.

Clinician Guide to Results (pdf 320.63 KB)

The Panorama test is a non-invasive prenatal screening test (NIPT) that uses SNP technology to calculate pregnancy-specific risks for common chromosomal aneuploidies. In certain circumstances, a patient’s result may state “unable to report.” Attached are details to help with the understanding of possible causes of these types of results.

Non-Invasive Prenatal Testing:  Megan P. Hall, PH.D. (pdf 446.68 KB)

The Panorama screening test offers superior overall performance when detecting Trisomy 21, Trisomy 18, Trisomy 13, Monosomy X, and fetal sex. The low false-positive rate will reduce the number of unnecessary invasive diagnostic procedures when compared to biochemical and ultrasound screen-ing methods, and offers early reassurance. Similarly, the low false-negative rate means that more affected pregnancies will be detected earlier, allowing mothers/parents and clinicians more time to prepare.

Non-Invasive Prenatal Screening for Microdeletion Syndromes – Megan P. Hall, PH.D. (pdf 265.81 KB)

Panorama, already established as a highly-accurate non-invasive screen for fetal whole-chromosome aneuploidies, has now been scientifically validated as a screening tool for the most common and severe microdeletions. As the incidence of microdeletion syndromes is not related to maternal age, it may be important to screen all pregnancies, not only those women of advanced maternal age. The initial panel of microdeletions includes 22q11.2 deletion (DiGeorge), 1p36, Cri-du-chat, Prader-Willi, and Angelman syndromes. This panel may expand in the future.

Importance of 22q11.2 Insert (pdf 633.06 KB)

22q11.2 deletion syndrome is more common than cystic fibrosis (22q11.2 deletion  syndrome occurs in approximately 1 in 2,000 live births) and can cause a wide variety of congenital anomalies as well as mild-to-moderate intellectual disabilities. Early childhood intervention can be critical for improving the quality of life of the child.

MFM Clinical Conundrum

Implications for 22q NIPT Screening for the MFM/Fetal Medicine Specialist 

by Professor McDonald-McGinn and Dr. Susan Gross

Early medical and developmental intervention can be critical in 22q (aka 22q11.2 deletion syndrome, or DiGeorge syndrome).Occurring in approximately 1 in 2,000 live births, 22q is more common than cystic fibrosis. However, until recently, it was rare for a fetus to be diagnosed with 22q before birth.In this webinar, the presenters discuss the importance of the early diagnosis of 22q in developing a lifelong treatment plan.

Click here to watch.


Learn about Non-Invasive Prenatal Screening Test (NIPT)

By Susan Gross, MD, FRCSC, FACOG, FACMG

With New Microdeletion Panel Option

In this recorded webinar, Dr. Gross presented the latest data on the Panorama NIPT and discussed: who might benefit from NIPT, why screen for microdeletions and how the information from positive tests for specific aneuploidies and microdeletions (such as XXY and 22q11.2 deletion) can improve care of the patient. Screening with Panorama and subsequent diagnostic confirmation may help guide the care of the child and lead to early intervention for the best possible outcome.

Click here to watch.


NIPT and Sex Chromosome Screening

Early Detection Means Early Treatment for Children with Developmental Delay due to X and Y Chromosome Aneuploidies 

by Carole Samango-Sprouse, Ed.D.

In this webinar Dr. Samango-Sprouse discusses the prevalence of X and Y chromosomal disorders, the high accuracy of Panorama™ in screening for sex chromosome aneuploidies, and the potential value of early intervention in improving the child’s quality of life.

Click here to watch.


SNP Method for NIPT

By Professor Kypros Nicolaides

NIPT aneuploidy and microdeletion screening, including screening for 22q

In this webinar Professor Kypros Nicolaides (King’s College, London University) reviews the 2014 clinical data on Panorama™, a SNP-based NIPT. The accuracy of this technology in screening for aneuploidies and microdeletions is discussed, with a focus on the importance of the need for early identification of 22q11.2 deletion syndrome (aka 22q, VCFS or DiGeorge syndrome).

Click here to watch.


Clinical Outcomes Study

By Dr. Peter Benn

Clinical Outcome Data

Dr. Benn presents the details on the largest ever NIPT clinical outcomes study with in-depth follow-up on 17,885 NIPT samples tested for trisomy 21, trisomy 18, trisomy 13, monosomy X, and in a subset of cases other sex chromosome aneuploidies (XXX, XXY, XYY), triploidy, and fetal sex. The results showed equivalent performance in low-risk and high-risk women. In addition there were no reports of incorrect fetal sex calls from >24,000 patients who requested fetal sex information and received low-risk reports.

Click here to watch.


2014 Clinical Trial Webinar

By Susan Gross, MD, FRCSC, FACOG, FACMG and Melissa Stosic, MS, CGC

Your questions answered

Our recent webinar was a review of the article about the Panorama™ clinical trial: “Single Nucleotide Polymorphism-Based Noninvasive Prenatal Screening in a High-Risk and Low-Risk Cohort” by E Pergament, et al. This was published in Obstetrics & Gynecology (the Green Journal) August 2014. This presentation was followed by a Q/A covering questions sent in by doctors from around the United States.

Click here to watch.


22q – What can you do?

By Donna McDonald-McGinn

Understanding this microdeletion syndrome

Did you know that 22q11.2 deletion syndrome (aka 22q or DiGeorge syndrome) is more common than cystic fibrosis and can cause a variety of mild to severe congenital anomalies and intellectual disabilities? Did you also know that prenatal diagnosis and early treatment may help prevent some of the more severe outcomes of this condition? Please view this webinar to learn more about this condition, and how you can help your patients and their newborns.

Click here to watch.


The Importance of Microdeletions

By Ronald Wapner, MD

Learn about the current research regarding identifying microdeletions

The level of prenatal care available to patients has been significantly enhanced with the new capability of the Panorama™ non-invasive prenatal test to screen for microdeletions.  Watch this informative two-part webcast to learn about:

  • Microdeletions, including what and how many there are, their significance, and the importance of detecting them.
  • The microdeletion validation  that demonstrates Panorama test’s high accuracy in screening for 5 microdeletion syndromes.

Click here to watch.


The Explosive Growth of NIPT: Why You Should Care About Fetal Fraction

by Brynn Levy, M.Sc. (Med). Ph.D., FACMG

Get the Facts about Fetal Fraction and NIPT Accuracy

New research reveals that low fetal fraction has an adverse effect on the accuracy of non-invasive prenatal screening tests (NIPTs) that use the traditional counting method. This webinar explains how low fetal fraction can trigger false negatives and why the accuracy of certain testing methods is compromised. Because most labs do not even report fetal fraction data, many doctors have not been made aware of the importance of fetal fraction as a factor in test results.

Watch this webinar to learn the facts about fetal fraction, how vastly the testing methods can differ on this important issue, and why the SNP-based method is able to maintain its accuracy even at low fetal fractions.

Click here to watch.