Letter From the President & Medical Directors - Fall 2016

This summer has brought several developments and activities in prenatal and carrier screening to the ever evolving standards and new practices relevant to our work with you.

The American College of Medical Genetics and Genomics (ACMG) updated their guidelines on noninvasive prenatal screening (NIPS) for fetal aneuploidy (Genetics in Medicine, advance online publication 28 July 2016, doi:10.1038/gim.2016.97). There are a variety of recommendations for clinicians and laboratories, the highlights of which are:

  • ACMG’s support for using cfDNA as a replacement for conventional screening for aneuploidies;
  • The crucial nature of pretest counseling for NIPS and the importance of going beyond discussion of trisomy 13, 18,and 21 to include information regarding screening for copy number variations (CNVs), exploration of patient preferences, and limitations of cfDNA testing;
  • Patients should be counseled regarding the availability of screening for sex chromosome aneuploidies and the implications of finding an increased risk of a sex chromosome aneuploidy, including higher false positive rates and clinical variability of outcomes;
  • All pregnant women should be informed of the distinctions between screening and diagnostic testing (CVS or amniocentesis) and informed that the latter is an option for the detection of chromosome abnormalities and clinically significant CNVs; 
  • Patients should understand the possible bases for a ‘no call’ result from cfDNA screening and be informed that diagnostic testing with chromosomal microarray analyses is an appropriate follow-up option; and,
  • cfDNA testing from different labs differ in their validity for assessing multiple gestations.

Insight’s practices have always been consistent with all of the ACMG and ACOG recommendations noted here as well as others at a more nuanced level from the ACMG Statement.  

Early Ultrasound Anatomy Scanning:  Insight has initiated a feasibility study for performing a detailed early anatomy scan at 13-14 weeks based on accumulating data regarding early anatomy scanning (EAS) during the 15-16 week window. The study, led by Jeff Dungan, MD as Principle Investigator, is applying the protocol standards of the “18-20 week scan” at these early weeks of the second trimester to assess the eventual application of EAS on a more routine basis for early detection of ultrasound anomalies. We are offering patients the opportunity to participate in the study at no cost if their primary OB’s use the Northwestern Memorial ultrasound services for their 18-20 week scans for follow-up confirmation data. We envision the eventual use of this early scan to be coupled with ongoing advances in cfDNA and other genetic testing. There is mounting data that early anatomic assessment allows for detection of a large proportion of gross structural anomalies. Conversely, normal findings (beyond the “nuchal”) provide some reassurance.

Ultrasound Screening and cfDNA Testing.  It has been Insight’s practice to do an ultrasound scan for nuchal translucency assessment on every patient receiving prenatal screening for aneuploidy, either by analyte or cfDNA analysis.  Our experience is that ~5% of women at 11-14 weeks are identified as having a fetus with an unexpected complication – including a structural anomaly, an enlarged nuchal fold, a demise, or other significant finding. We have structured the ‘flow’ of a patient’s visit to start with the scan so that the genetic counseling that follows can be shaped accordingly. Our experience with performing this scan is consistent with the findings of Reiff et al recently published in Prenatal Diagnosis (36:260-265, 2016).  

Carrier Screening: A paper very recently published in JAMA (Haque, IS et al, 316:734-742, 2016) modeled the data generated from almost 347,000 individuals screened by an ‘expanded carrier screening panel’ comprised of conditions with severe or profound phenotypes. This paper reports several very important findings:

  • Current guidelines will miss as many as 94% of pregnancies affected by an autosomal recessive condition depending upon ethnicity; and, 
  • Approximately 1 in 550 pregnancies will be affected by a severe or profound condition; this figure compares to a general risk of 1 in 700 births for Down syndrome and 1 in 1,000 births for an open neural tube defect. 
  • Other data from the study also underscore the value of the pre-and post-test counseling that should accompany such screening. The value of sequenced-based screening vs. targeted mutation screening is also highlighted. We strongly encourage you to offer your patients sequenced and targeted reflex testing which Insight can provide even if you are not using us for your initial carrier screening.

On the more local front – Insight will be opening its 6th and 7th offices in Naperville and Orland Park around mid-October. We will be accessible to patients to provide prenatal, preconception, and hereditary cancer genetic counseling, screening, and testing from the northern, northwest, western, southwest, and southern suburbs as well as in the city at 680 N. Lakes Shore Drive and Swedish Covenant Hospital.


Morris Fiddler, PhD
Jeffrey Dungan, MD, FACOG, FACMG
Lee Shulman, MD, FACOG, FACMG