Elena Ashkinadze

Exome sequencing positively identified relevant alterations in more than half of cases with an indication of prenatal ultrasound anomalies

Exome sequencing is a successful option for diagnosing individuals with previously uncharacterized genetic conditions, however little has been reported regarding its utility in a prenatal setting. The goal of this study is to describe the results from a cohort of fetuses for which exome sequencing was performed.

Genetic Counselors’ Perspectives and Practices Regarding Expanded Carrier Screening after Initial Clinical Availability

Expanded carrier screening (ECS), introduced in 2009, identifies carriers for dozens or hundreds of recessive diseases. At the time of its introduction into clinical use, perspectives of the genetic counseling community regarding ECS were unknown. We conducted a survey in early 2012 of GCs and report the results here. They represent a snapshot of opinions and usage at that time, providing a baseline for comparison as the technology continues to evolve and as usage increases. The survey assessed personal perspectives, opinions on clinical implementation and clinical utilization of ECS. The sample included 337 GCs of varying clinical fields, of whom 150 reported practicing in reproductive settings. Our findings demonstrate that, at the time, GCs indicated general agreement with ECS as a concept – for example, most GCs agreed that carrier screening should address diseases outside of current guidelines and also indicated personal interest in electing ECS. There were also disagreements or concerns expressed regarding appropriate pre- and post-test counseling (e.g., the content and delivery mode of adequate informed consent) and practical implementation (e.g., the amount of time available for follow-up care). This was the first quantitative study of a large number of GCs and it revealed initial overall support for ECS among the GC profession. The authors plan to re-administer a similar survey, which may reveal changes in opinions and/or utilization over time. A follow up survey would also allow further exploration of questions uncovered by these data.

Successful conservative management of hereditary hemorrhagic telangiectasia in pregnancy. A case report.

Background: Hereditary hemorrhagic telangiectasia (HHT) is a condition characterized by multiple telangiectases and arteriovenous malformations. Women with HHT may develop life-threatening complications in pregnancy. In particular, death from pulmonary hemorrhage has been reported. Consequently, these women are often advised not to conceive or to terminate their pregnancies. Case: We report a case of conservative management of HHT in pregnancy with a good outcome. Conclusion: This case demonstrates that in carefully selected cases, women with HHT who are managed conservatively may have good pregnancy outcomes. A diagnosis of HHT alone is not reason to advise women against pregnancy, nor should these women routinely be advised to undergo pregnancy termination.

Discordant Embryonic Aneuploidy Testing and Prenatal Ultrasonography Prompting Androgen Insensitivity Syndrome Diagnosis

BACKGROUND: Multimodal prenatal screening for developmental pathology is increasingly common. In this case, definitive prenatal diagnosis of androgen insensitivity syndrome was diagnosed after discordant results from karyotypes determined by embryonic preimplantation genetic screening and antenatal ultrasound results. CASE: A 38-year-old woman, gravida 2 para 0010, undergoing in vitro fertilization with preimplantation genetic screening transferred one male and one female embryo. An anatomic ultrasonogram revealed two fetuses with female genitalia. Cell-free fetal DNA analyzed using noninvasive prenatal screening demonstrated Y chromosome material, and amniocentesis confirmed one 46,XX and one 46,XY fetus. Sequencing of the androgen receptor for the 46,XY fetus identified a mutation. CONCLUSION: With increased use, discordance among prenatal testing modalities such as preimplantation genetic screening, noninvasive prenatal screening, and ultrasonography will become more common requiring expert navigation to identify true pathology.

The significance of a positive second trimester serum screen for trisomy 18

Objectives. We designed this study to estimate the proportion of fetuses in pregnancies with positive second trimester serum screens for trisomy 18 who actually have trisomy 18, to estimate the proportion of women with trisomy 18 who have a negative serum screen, and to assess the role of ultrasound in the diagnosis of trisomy 18. Methods. Retrospective study of two cohorts of pregnant women in 2004 and 2005: (1) those with a second trimester serum screen positive for trisomy 18 and (2) those with fetuses having trisomy 18. Results. There were 93 women with positive serum screens for trisomy 18. Of these, only three had a fetus with trisomy 18. There were five other cases of trisomy 18, three of which had a negative second trimester serum screen for trisomy 18. All fetuses with trisomy 18 had multiple major structural abnormalities detected on targeted genetic sonography. Conclusions. A positive second trimester serum screen has a poor sensitivity and poor prediction for trisomy 18. Trisomy 18 is highly unlikely if a woman with a positive screen for trisomy 18 has no fetal abnormalities detected on targeted genetic sonography. Women with a positive second trimester serum screen for trisomy 18 should be offered genetic sonography, and the practice of routine amniocentesis for all women with a positive screen should be discouraged when targeted genetic sonography is available.

Trends in invasive prenatal diagnostic testing at a single institution

As diagnostic methodologies evolve, we sought to determine whether invasive testing rates would decline, whether there would be a shift in indications for invasive testing, and whether the diagnostic yield would increase.