November 2020

Message From Outgoing Chairs 

By Diane Van Opstal and Elaine Holgado

Sadly, as the 2020 ISPD conference was one of the many cancelled events of 2020, we were not able to conduct our final SIG meeting in person. So we would like to take the opportunity to say farewell and thank you to all those that participated in the meetings, and to those who have viewed the content on the SIG page on the ISPD website and read our contributions to Global Updates.

We are handing over the reins to Francesca Romana Grati, PhD, who we are sure everyone knows well due to her roles in ISPD including her recent ISPD Director role and her work with NIPT, CMA, and mosaicism. Her co-chair is Natalie Chandler, PhD, from Great Ormond Street Hospital in London who works predominantly in the fields of prenatal exome sequencing and NIPD.

We started chairing the Laboratory Techniques SIG in 2017 at the International Conference in San Diego. During this meeting we invited Dr. Sandi Deans to speak to the group to give an update on EQA schemes offered by NEQAS (now GenQA). This was the year the pilot scheme for NIPT was launched, and it was remarkably interesting and informative to hear from Sandi about this scheme in particular and how it was established. The opportunity for feedback from a large group of scientists performing NIPT made for a very useful group discussion! NIPT was the main focus of this SIG. Since then, Sandi became a fixture at each of our SIG meetings reflecting the importance of quality in the work of the laboratory. During this first SIG we also had the opportunity to collect and discuss ideas on topics for educational events that we could propose to the ISPD Board. This led to the organization of a well-attended preconference course at the Antwerp meeting in 2018 (Course 6 - Navigate cfDNA Testing Options: Technical, biological and quality aspects of different cfDNA testing technologies). Ideas for pre-conference meetings and for collaborative research were forthcoming in each of the SIG meetings which is one of the aims of the meetings. This ensures the meetings remain relevant to the attendees and all ideas and suggestions are passed onto the ISPD Board.

The focus of our second SIG meeting in 2018 was Chromosomal MicroArray where discussions around reporting differences between laboratories in different countries and between pre- and postnatal samples were held. 

After our second SIG meeting, the format changed to a longer meeting over breakfast rather than a lunchtime meeting. This provided the opportunity for more invited speakers as this was a successful element of all the SIG meetings. Natalie herself gave an excellent presentation on the laboratory issues encountered when implementing rapid fetal whole exome sequencing in the laboratory at the 2019 SIG meeting in Singapore. WES was the focus of this third meeting.

We have thoroughly enjoyed chairing these SIG meetings and getting to know more members of the group. We are excited to see what Drs. Grati and Chandler present at the next and future SIGs!

Thank you to all those who attended, presented, and contributed to this SIG and especially to Dr. Francesca Romana Grati for her support and advice as Board liaison during our time as Co-chairs.

We want to draw your attention to a few papers on prenatal exomes and NIPT that recently were published in Prenatal Diagnosis.

Prenatal Exomes

Natalie Chandler, PhD

The clinical utility of prenatal exome sequencing continues to be evaluated in laboratories worldwide with a number of studies on specific anomalies showing a range of diagnostic yields. Those with yields below 10% include isolated nuchal translucency (5.5%) (Yang, et al DOI: 10.1002/pd.5789) and non-immune hydrops (4.2%) (Deng, et al 2020 DOI: 10.1002/pd.5789). Those with higher yields include cerebellar vermis hypoplasia (42%) (Li, et al DOI: 10.1002/pd.5732), anomalies of the kidney and urinary tract (12.3%) (Lei, et al DOI: 10.1002/pd.5737) and multiple structural anomalies (19%) (Corsten-Janssen, et al DOI: 10.1002/pd.57801. Deden, et al. DOI: 10.1002/pd.5717 did a multisystem study showing higher diagnostic yields in the skeletal dysplasia (61%) and multiple anomalies groups (22%). As prenatal exome sequencing is being implemented in a clinical setting, these studies provide useful evidence to determine which patients would be of greater benefit if resources are limited. 

Prenatal Diagnosis of Sex Discordance

Francesca Romana Grati, PhD

Prenatal diagnosis of sex discordance is a relatively new phenomenon that has been acquiring more and more relevance consequently to widespread integration of cell-free DNA testing into modern antenatal screening. Prior to cfDNA testing, the diagnosis of a disorder of sexual differentiation was consequent to either the identification of ambiguous genitalia at the second trimester morphology ultrasound scan or to the discovery of a genotype-phenotype discordance in cases where invasive prenatal diagnosis (or, more recently, preimplantation genetic testing) has been undertaken. Discordant fetal sex identification and early prenatal diagnosis of fetal sex are now more common, with a prevalence of approximately 1 in 1500-2000 pregnancies. 

Given the need to deal with this new type of cfDNA testing discordant result, Smet ME, Scott FP, McLennan AC. (Prenat Diagn. 2020 Mar 3. DOI: 10.1002/pd.5676) have published a comprehensive overview of various causes of discordant fetal sex on cfDNA and ultrasound. They also propose an algorithm to approach the diagnosis and management of genotype-phenotype discordance. As sex discordance can be due to multiple causes, some of which are easily diagnosed, while others are unable to be diagnosed antenatally, a multidisciplinary approach is necessary to assist with diagnosis and ongoing management.