Search

Background: Exome sequencing in prenatal context confronts with pathogenic variants associated with phenotypes that are not detectable prenatally. Materials and Methods: A consanguineous couple was referred at 24 weeks of gestation for prenatal genetic investigations after ultrasonography findings including decreased fetal movements, hypoplastic male external genitalia, retrognathia, prefrontal edema, anomalies of the great vessels with pulmonary atresia and dilated tortuous aorta. Result: Prenatal trio exome sequencing identified two homozygous likely pathogenic variants, i.e. a missense in EFEMP2 involved in cutis laxa and a nonsense in RAG1 involved in several types of severe combined immunodeficiency. Discussion: The fetal ultrasonographic phenotype was partially compatible with previously reported prenatal presentations secondary to EFEMP2 biallelic variants, but prenatal presentations have never been reported for RAG1 related disorders because the RAG1 phenotype is undetectable during pregnancy. Conclusion: Both EFEMP2 and RAG1 variants were disclosed to the couple because the EFEMP2 variant was considered causative for the fetal ultrasonographic phenotype and the RAG1 variant was considered a finding of strong interest for genetic counselling and monitoring of future pregnancies following the American College of Medical Genetics and Genomics recommendations about the discovery of incidental findings in fetal exome sequencing in prenatal diagnosis. [ABSTRACT FROM AUTHOR]

A consanguineous couple was referred at 10 weeks of gestation (WG) for prenatal genetic investigations due to isolated cystic hygroma. Prenatal trio exome sequencing identified causative homozygous truncating variants in ASCC1 previously implicated in spinal muscular atrophy with congenital bone fractures. Prenatal manifestations in ASCC1 can usually include hydramnios, fetal hypo‐/akinesia, arthrogryposis, contractures and limb deformities, hydrops fetalis and cystic hygroma. An additional truncating variant was identified in CSPP1 associated with Joubert syndrome. Presentations in CSPP1 include cerebellar and brainstem malformations with vermis hypoplasia and molar tooth sign, difficult to visualize in early gestation. A second pregnancy was marked by the recurrence of isolated increased nuchal translucency at 10 + 2 WG. Sanger prenatal diagnosis targeted on ASCC1 and CSPP1 variants showed the presence of the homozygous familial ASCC1 variant. In this case, prenatal exome sequencing analysis is subject to a partial ASCC1 phenotype and an undetectable CSPP1 phenotype at 10 weeks of gestation. As CSPP1 contribution is unclear or speculative to a potentially later in pregnancy or postnatal phenotype, it is mentioned as a variant of uncertain significance. The detection of pathogenic or likely pathogenic variants involved in severe disorders but without phenotype‐genotype correlation because the pregnancy is in the early stages or due to prenatally undetectable phenotypes, will encourage the clinical community to define future practices in molecular prenatal reporting. Key points: What's already known about this topic? Homozygous pathogenic truncating variants in ASCC1 were previously implicated in spinal muscular atrophy with congenital bone fractures.Homozygous pathogenic truncating variants in CSPP1 were previously implicated in Joubert syndrome. What does this study add? This report confirms cystic hygroma as ASCC1 associated fetal presentation.Detection of pathogenic or likely pathogenic variants involved in severe disorders but without phenotype‐genotype correlation because the pregnancy is in the early stages or due to prenatally undetectable phenotypes will encourage the clinical community to define future practices in molecular prenatal reporting. [ABSTRACT FROM AUTHOR]

Objective: To assess the contribution and impact of fetal magnetic resonance imaging (MRI) in managing fetal gastroschisis. Methods: We conducted an observational retrospective study of gastroschisis patients at three fetal medicine centers from 2008 to 2019. The primary endpoint was the number of cases in which the MRI provided relevant information related to gastroschisis. Results: A total of 189 patients were included, and our study group included 38 patients who underwent MRI. For the eight patients with suspected gastroschisis, MRI confirmed the diagnosis. In six cases, it provided additional relevant information (spiral turn, intestine ischemia, and bowel size discrepancy). For the 17 patients with ultrasound signs of additional gastrointestinal anomalies, MRI detected one case of unidentified complex gastroschisis on sonography. For the 13 patients undergoing routine MRI, no significant information was obtained. One termination of pregnancy and one fetoscopy were performed a few days after the MRI results. There was no subsequent follow‐up or additional bowel complications to support management. Conclusion: Although MRI did not change the management of pregnancies complicated by fetal gastroschisis, patients presenting with fetal gastroschisis with intraabdominal bowel dilatation could benefit from MRI to allow for more precise prenatal counseling to predict postnatal intestinal complications before birth. Key points: What's already known about this topic?The antenatal management of gastroschisis is based on ultrasonography and non‐stress testing.Intraabdominal bowel dilatation has been proposed as the main predictor of outcome for complex gastroschisis.Indications for MRI in gastroschisis are not well‐defined. What does this study add?Performing magnetic resonance imaging (MRI) did not modify the management of pregnancy in most cases.In more than 20% of cases (8/38), performing MRI could specify the anatomical injury complicating gastroschisis when associated with intraabdominal dilatation of the intestinal loops.It can help to refine the prenatal counseling and postnatal care protocols.MRI is only indicated in the third trimester in cases of complex gastroschisis. [ABSTRACT FROM AUTHOR]