Trio exome sequencing is highly relevant in prenatal diagnostics.

OBJECTIVE: About 3% of newborns show malformations, with about 20% of the affected having genetic causes. Clarification of genetic diseases in postnatal diagnostics was significantly improved with high-throughput sequencing, in particular through whole exome sequencing covering all protein-coding regions. Here, we aim to extend the use of this technology to prenatal diagnostics. METHOD: Between 07/2018 and 10/2020, 500 pregnancies with fetal ultrasound abnormalities were analyzed after genetic counseling as part of prenatal diagnostics using WES of the fetus and parents. RESULTS: Molecular genetic findings could explain ultrasound abnormalities in 38% of affected fetuses. In 47% of these, disease-causing de novo variants were found. Pathogenic variants in genes with autosomal recessive or X-linked inheritance were detected in more than one-third (70/189 = 37%). The latter are associated with increased probability of recurrence, making their detection important for further pregnancies. Average time from sample receipt to report was 12 days in the recent cases. CONCLUSION: Trio exome sequencing is a useful addition to prenatal diagnostics due to its high diagnostic yield and short processing time (comparable to chromosome analysis). It covers a wide spectrum of genetic changes. Comprehensive interdisciplinary counseling before and after diagnostics is indispensable.

Three-dimensional multi-slice view: new prospects for evaluation of congenital anomalies in the fetus.

OBJECTIVES: The purpose of this study was to describe the use and potential of Multi-Slice View 3-dimensional (3D) ultrasonographic software (Medison Co, Ltd, Seoul, Korea) in showing fetal congenital anomalies. METHODS: Fetuses with congenital anomalies diagnosed by means of 2-dimensional ultrasonography were prospectively included in the study. Good-quality 3D volumes of the region of interest were obtained in each case. Subsequently, these volumes were reviewed with use of 3D eXtended Imaging with Multi-Slice View and SonoMR (Medison Co, Ltd). Image processing was performed through the use of off-line software (Medison XI Viewer, version 1.0.0.218). RESULTS: A total of 6 fetuses (median gestational age, 27 weeks; range, 16-35 weeks) with the following anomalies were examined: dacryocystocele, esophageal atresia, right-sided aortic arch, hydrometrocolpos, horseshoe kidney, and hemivertebra. Images of diagnostic quality were obtained from all patients. According to the respective underlying anomalies and the positions of the fetuses, images were obtained from the initial axial plane in 2 cases (esophageal atresia and right-sided aortic arch) and from reconstructed planes in the remaining 4 cases (dacryocystocele, hydrometrocolpos, horseshoe kidney, and hemivertebra). CONCLUSIONS: Three-dimensional Multi-Slice View can deliver informative images of the region of interest regardless of fetal position. It may be particularly helpful for evaluation of difficult anomalies in the fetus.