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Observational Study
. 2020 Jul;40(8):972-983.
doi: 10.1002/pd.5717. Epub 2020 May 5.

Rapid whole exome sequencing in pregnancies to identify the underlying genetic cause in fetuses with congenital anomalies detected by ultrasound imaging

Chantal Deden  1   2 , Kornelia Neveling  1 , Dimitra Zafeiropopoulou  3 , Christian Gilissen  3 , Rolph Pfundt  4 , Tuula Rinne  4 , Nicole de Leeuw  4 , Brigitte Faas  1 , Thatjana Gardeitchik  3 , Suzanne C E H Sallevelt  5 , Aimee Paulussen  5 , Servi J C Stevens  5 , Esther Sikkel  6 , Mariet W Elting  7 , Merel C van Maarle  8 , Karin E M Diderich  9 , Nicole Corsten-Janssen  2 , Klaske D Lichtenbelt  10 , Guus Lachmeijer  10 , Lisenka E L M Vissers  4 , Helger G Yntema  4 , Marcel Nelen  1 , Ilse Feenstra  1 , Wendy A G van Zelst-Stams  1
Affiliations
Observational Study

Rapid whole exome sequencing in pregnancies to identify the underlying genetic cause in fetuses with congenital anomalies detected by ultrasound imaging

Chantal Deden et al. Prenat Diagn. 2020 Jul.

Abstract

Objective: The purpose of this study was to explore the diagnostic yield and clinical utility of trio-based rapid whole exome sequencing (rWES) in pregnancies of fetuses with a wide range of congenital anomalies detected by ultrasound imaging.

Methods: In this observational study, we analyzed the first 54 cases referred to our laboratory for prenatal rWES to support clinical decision making, after the sonographic detection of fetal congenital anomalies. The most common identified congenital anomalies were skeletal dysplasia (n = 20), multiple major fetal congenital anomalies (n = 17) and intracerebral structural anomalies (n = 7).

Results: A conclusive diagnosis was identified in 18 of the 54 cases (33%). Pathogenic variants were detected most often in fetuses with skeletal dysplasia (n = 11) followed by fetuses with multiple major fetal congenital anomalies (n = 4) and intracerebral structural anomalies (n = 3). A survey, completed by the physicians for 37 of 54 cases, indicated that the rWES results impacted clinical decision making in 68% of cases.

Conclusions: These results suggest that rWES improves prenatal diagnosis of fetuses with congenital anomalies, and has an important impact on prenatal and peripartum parental and clinical decision making.

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Conflict of interest statement

The authors report no conflict of interest with this work.

Figures

FIGURE 1
FIGURE 1
Overview of total diagnostic yield and per indication of identified fetal congenital anomalies. Graphical representation of the overall diagnostic yield of prenatal rapid whole exome sequencing. In addition, the yields of each clinical indication are provided. Diagnostic yields were compared to one another to assess whether diagnostic yields differed by clinical cohort. Only statistical significant comparisons are indicated (*: P < .05; **: P < .01; ***: P < .005), highlighting that overall, the fetuses with “other” clinical features than skeletal dysplasia, multiple fetal ultrasound anomalies or intracerebral structural anomalies have a reduced chance on a diagnosis
FIGURE 2
FIGURE 2
Impact of rWES on clinical decision making. Schematic overview of the impact of rWES outcome on clinical decision making. Three main categories for requesting rWES were identified. In each category, rWES impact clinical decision making. From this analysis, it can be clearly shown that rWES impacts clinical decision making, even in the absence of a diagnosis. rWES, rapid whole exome sequencing
See this image and copyright information in PMC

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