BackgroundExome sequencing is now being incorporated into clinical care for pediatric and adult populations, but its integration into prenatal diagnosis has been more limited. One reason for this is the paucity of information about the clinical utility of exome sequencing in the prenatal setting.MethodsWe retrospectively reviewed indications, results, time to results (turnaround time, TAT), and impact of exome results for 146 consecutive “fetal exomes” performed in a clinical diagnostic laboratory between March 2012 and November 2017. We define a fetal exome as one performed on a sample obtained from a fetus or a product of conception with at least one structural anomaly detected by prenatal imaging or autopsy. Statistical comparisons were performed using Fisher’s exact test.ResultsPrenatal exome yielded an overall molecular diagnostic rate of 32% (n = 46/146). Of the 46 molecular diagnoses, 50% were autosomal dominant disorders (n = 23/46), 41% were autosomal recessive disorders (n = 19/46), and 9% were X-linked disorders (n = 4/46). The molecular diagnostic rate was highest for fetuses with anomalies affecting multiple organ systems and for fetuses with craniofacial anomalies. Out of 146 cases, a prenatal trio exome option designed for ongoing pregnancies was performed on 62 fetal specimens, resulting in a diagnostic yield of 35% with an average TAT of 14 days for initial reporting (excluding tissue culture time). The molecular diagnoses led to refined recurrence risk estimates, altered medical management, and informed reproductive planning for families.ConclusionExome sequencing is a useful diagnostic tool when fetal structural anomalies suggest a genetic etiology, but other standard prenatal genetic tests did not provide a diagnosis.Electronic supplementary materialThe online version of this article (10.1186/s13073-018-0582-x) contains supplementary material, which is available to authorized users.

Despite having experienced complexity and identified challenges of the reproductive genetic counseling, availability of diagnostic WES contributed important information that aided in prenatal care planning and decision-making. Future enhanced provider education and larger studies to systematically study the integration of WES in reproductive genetic counseling and prenatal care will be important.

An omphalocele is a congenital defect in the abdominal wall characterized by absent abdominal muscles, fascia, and skin. The characteristic ultrasound appearance includes a midline defect with herniation of abdominal contents into the base of the umbilical cord. Other anatomic abnormalities are seen in approximately 50% of cases, most notably cardiac defects (19%-32%). Approximately, 50% of cases are associated with genetic and multiple malformation syndromes including trisomy 13/18, pentalogy of Cantrell and Beckwith-Wiedemann syndrome. Therefore, a thorough evaluation is recommended, including detailed anatomic survey, fetal echocardiogram, genetic counseling, and prenatal diagnostic testing. Overall prognosis depends on the size of the omphalocele, genetic studies, and associated anomalies. Early prenatal diagnosis remains important in order to provide parental counseling and assist in pregnancy management. Delivery should occur at a tertiary care center. Timing and mode of delivery should be based on standard obstetric indications with cesarean delivery reserved for large omphalocele (>5 cm) or those that involve the fetal liver. Neonatal management involves either primary or staged reduction, both of which can be associated with a prolonged neonatal hospitalization. Key Points What is already known about this topic? � Omphalocele can be accurately diagnosed on prenatal ultrasound � A significant proportion of omphalocele cases are associated with chromosomal abnormalities or genetic syndromes � Isolated cases of small omphalocele can be associated with a good prognosis � In the absence of other obstetric indications delivery should be at term What does this study add? � The role of magnetic resonance imaging for prognostic prediction remains unclear. � Further studies are needed to determine the role of stated exome sequencing. 1 | INTRODUCTION Omphalocele is one of the most common types of abdominal wall defects. With improved sensitivity of prenatal ultrasound and expanding prenatal diagnostic options, clinicians are tasked with not only providing the diagnosis, but counseling the patient regarding prenatal and postnatal management options. In this manuscript, we review the essential points for counseling when the diagnosis of fetal omphalocele is made in order to answer common questions that might arise in discussion with parents. Ideally, counseling should be provided by a multidisciplinary team consisting of obstetricians, genetic counselors, maternal-fetal medicine specialists, neonatologists, and pediatric surgeons.

Wolf–Hirschhorn syndrome (WHS) is caused by partial deletion of the short arm of chromosome 4 and is characterized by dysmorphic facies, congenital heart defects, intellectual/developmental disability, and increased risk for congenital diaphragmatic hernia (CDH). In this report, we describe a stillborn girl with WHS and a large CDH. A literature review revealed 15 cases of WHS with CDH, which overlap a 2.3-Mb CDH critical region. We applied a machine-learning algorithm that integrates large-scale genomic knowledge to genes within the 4p16.3 CDH critical region and identified FGFRL1, CTBP1, NSD2, FGFR3, CPLX1, MAEA, CTBP1-AS2, and ZNF141 as genes whose haploinsufficiency may contribute to the development of CDH.

Background: Cardiovascular disease is the leading cause of death among women. Sex-specific risk factors for cardiovascular disease include history of a hypertensive disorder of pregnancy. Problem: After diagnosis of a hypertensive disorder of pregnancy, professional societies recommend follow-up with a primary care provider for preventative care. There are gaps in patient and health care provider knowledge of the association between a hypertensive disorder of pregnancy and cardiovascular disease. That gap has a negative effect on patients receiving recommended follow-up. Methods: An electronic registry was created to identify those who gave birth in our health system and had a diagnosis of hypertensive disorder of pregnancy. From this, information outreach was sent electronically to the patient and their primary care provider. Interventions: Communication in the outreach included education on the association between hypertensive disorders of pregnancy and cardiovascular disease, the importance of follow-up, cardiopreventative strategies, and biochemical assessment. Medical records were audited at approximately 6 months postpartum to determine if patients completed a visit with their primary care provider to discuss cardiovascular risks. Results: Between May 2021 and June 2022, 15% (n = 1,131) of patients who gave birth in our health system had a diagnosis of hypertensive disorder of pregnancy. Ninety percent of those patients who received outreach communication viewed the letter. At baseline, 16% of patients during postpartum with a hypertensive disorder of pregnancy saw their primary care provider to discuss cardiopreventative strategies. After implementation of our program, 26% of those with a hypertensive disorder of pregnancy saw their primary care provider for follow-up and discussed cardiopreventative strategies. Clinical Implications: Nurses should ensure that women during postpartum and their primary care providers are educated about the association of hypertensive disorders of pregnancy and long-term cardiovascular risk. The electronic health record may be an optimal way to ensure education is provided and follow-up scheduled.