Utility of Expanded Carrier Screening in Pregnancies With Ultrasound Abnormalities

Abstract

Routine screening with prenatal ultrasound is now recommended in all pregnancies due in part to the 3% risk for congenital anomalies. Detected anomalies that receive a prenatal diagnosis can benefit from more targeted prenatal and postnatal care recommendations. In addition to cell-free DNA screening for aneuploidy, an additional noninvasive method for evaluating a pregnancy in search of possible single-gene disorders is expanded carrier screening (ECS). This study's aim was to evaluate whether ECS is of utility in assessing fetal ultrasound abnormalities.The study was based on a retrospective chart review of genetic testing results in infants born with congenital structural abnormalities between January 1, 2014 and December 31, 2017. The authors collected genetic testing results to determine whether ECS would potentially have helped point to the genetic diagnosis. Inclusion requirements included patients who underwent evaluation by a medical geneticist within the first 6 months of life due to the presence of a structural abnormality potentially detectable by prenatal ultrasound. Infants diagnosed with an X-linked or autosomal recessive disorder were included to determine whether the disorder would have been detected using a clinically available ECS panel. The authors considered 2 different ECS panels: one was available in 2017 and included 271 conditions, and the other was available after 2020 and included 500 autosomal recessive and X-linked conditions. In addition, after the composition of the initial list of 271 autosomal recessive and X-linked conditions, a literature search in both PubMed and OMIM also yielded further data of potential phenotypes for analysis.The review revealed that 931 subjects met inclusion criteria; after exclusion of those infants that did not have a structural anomaly potentially detectable by prenatal ultrasound, those that did not have genetic testing, and those with a negative result, there were 222 infants with positive genetic results that were thought to have likely caused the phenotype. Among these, 42 (18.9%) were specifically diagnosed with single-gene disorders potentially detectable by carrier screening, including 8 unique autosomal recessive conditions and 6 X-linked conditions. Of the 14 unique genetic conditions, 3 were available on the initial 271-condition panel, whereas 5 disorders could have been detected by ECS in the 500-condition panel. Overall, 222 patients with a structural abnormality identifiable by prenatal ultrasound had a genetic diagnosis. Of these, 6 cases (2.7%) were detectable using a 500-condition ECS panels, compared with 4 (1.8%) with a 271-condition panel. Among the 41 cases of single-gene disorders, a 500-condition ECS panel could potentially have detected 14.6% of cases, whereas a 271-condition panel could have detected 9.8%.Ultimately, the data demonstrated that the utility of ECS in detecting single-gene disorders seemed to be very limited when compared with exome sequencing. However, ECS could be a useful tool for detecting conditions that are ...

Expanded carrier screening in the United States: A systematic evidence review exploring client and provider experiences

“…A recent study by Stevens et al (2021) did explore the utility of ECS in the presence of a fetal anomaly and of their client population who pursued genetic testing, 3.2% were identified to have an AR or XL condition that would have been screened for by a clinically available 500‐condition ECS panel. Thus, there is potential utility in ECS to narrow down the differential diagnosis in a prenatal setting.…”