Second-trimester prenatal diagnosis of Nager syndrome with a deletion including detected by chromosomal microarray.

Nager syndrome is a rare, complex malformation syndrome, for which there is limited information on prenatal genetic testing. Clinical diagnosis of Nager syndrome, which can be caused by deletions encompassing SF3B4 gene, is possible prenatally. Prenatal chromosomal microarray can aid genotype-phenotype correlation in pregnancies with structural abnormalities seen on ultrasound.

Evolution of a prenatal genetic clinic-A 10-year cohort study.

Objective: To (a) evaluate the proportion of women where a unifying genetic diagnosis was obtained following assessment of an observed pattern of fetal anomalies and (b) assess trends in genetic testing in a joint fetal-medicine genetic clinic.

Method: Retrospective cohort study of all women attending the clinic. Outcomes included (a) indication for referral, (b) genetic test performed and (c) diagnoses obtained.

Exome Sequencing for Prenatal Detection of Genetic Abnormalities in Fetal Ultrasound Anomalies: An Economic Evaluation.

Introduction: In light of the prospective Prenatal Assessment of Genomes and Exomes (PAGE) study, this paper aimed to determine the additional costs of using exome sequencing (ES) alongside or in place of chromosomal microarray (CMA) in a fetus with an identified congenital anomaly.

Methods: A decision tree was populated using data from a prospective cohort of women undergoing invasive diagnostic testing. Four testing strategies were evaluated: CMA, ES, CMA followed by ES ("stepwise"); CMA and ES combined.

Prenatal chromosomal microarray testing of fetuses with ultrasound structural anomalies: A prospective cohort study of over 1000 consecutive cases.

Objective: Evaluate the diagnostic yield of prenatal submicroscopic chromosome anomalies using prenatal array comparative genomic hybridisation (aCGH).

Method: Prospective cohort study conducted between March 2013 and June 2017 including fetuses where an elevated nuchal translucency (NT) or structural anomaly was identified on ultrasound and common aneuploidy testing was negative. aCGH was performed using an 8-plex oligonucleotide platform with a genome wide backbone resolution of greater than 200 kb and interpretation in line with American College of Medical Genetics guidance.

Exome sequencing in the assessment of congenital malformations in the fetus and neonate.

Major congenital anomalies are often associated with perinatal mortality, long-term morbidity and prolonged hospitalisation. Prenatal ultrasound remains the principle diagnostic test for many anomalies, but despite this up to one-third are only identified in the neonatal period. The primary step in determining underlying aetiology is to define accurately the phenotype by recognition of dysmorphology (both prenatally and postnatally).

Prenatal exome sequencing analysis in fetal structural anomalies detected by ultrasonography (PAGE): a cohort study.

Background: Fetal structural anomalies, which are detected by ultrasonography, have a range of genetic causes, including chromosomal aneuploidy, copy number variations (CNVs; which are detectable by chromosomal microarrays), and pathogenic sequence variants in developmental genes. Testing for aneuploidy and CNVs is routine during the investigation of fetal structural anomalies, but there is little information on the clinical usefulness of genome-wide next-generation sequencing in the prenatal setting. We therefore aimed to evaluate the proportion of fetuses with structural abnormalities that had identifiable variants in genes associated with developmental disorders when assessed with whole-exome sequencing (WES).

Clinical utility of exome sequencing in the prenatal diagnosis of congenital anomalies: A Review.

Advances in prenatal genomics have enabled the assessment of not only the sub-microscopic structure of chromosomes using chromosomal microarray analysis, but also the detection of "pathogenic variants" to the resolution of a single base pair with the use of next generation sequencing. Research is emerging on the additional prenatal diagnostic yield that exome sequencing offers when structural fetal anomalies are detected on ultrasound examination, in particular the identification of monogenic abnormalities defining prognosis and recurrence of anomalies. Primarily assessed using fetal DNA obtained by invasive techniques (amniocytes or chorionic villi), this technology is progressing into a non-invasive approach using maternal plasma.

Molecular autopsy by trio exome sequencing (ES) and postmortem examination in fetuses and neonates with prenatally identified structural anomalies.

Purpose: To determine the diagnostic yield of combined exome sequencing (ES) and autopsy in fetuses/neonates with prenatally identified structural anomalies resulting in termination of pregnancy, intrauterine, neonatal, or early infant death.

Methods: ES was undertaken in 27 proband/parent trios following full autopsy. Candidate pathogenic variants were classified by a multidisciplinary clinical review panel using American College of Medical Genetics and Genomics (ACMG) guidelines.

The first antenatal diagnosis of KBG syndrome: a microdeletion at chromosome 16q24.2q24.3 containing multiple genes including ANKRD11 associated with the disorder.

The loss of ANKRD11 gene confirms the diagnosis of KBG syndrome but does not elucidate the pediatric phenotype providing a counseling challenge. With the expansion of prenatal diagnosis, and the potential to perform whole-exome sequencing antenatally, we must describe the genetic abnormalities, antenatal ultrasound findings, and phenotype concurrently to facilitate counseling.

Parental experiences of prenatal whole exome sequencing (WES) in cases of ultrasound diagnosed fetal structural anomaly.

Objective: To explore parental experiences of whole exome sequencing (WES) for prenatal diagnosis and ascertain what influenced their decision-making to undergo testing.

Method: Twelve women comprised a purposeful sample in a series of semistructured interviews. All had received a fetal anomaly diagnosis on ultrasound.

Prenatal Detection of PIK3CA-related Overgrowth Spectrum in Cultured Amniocytes Using Long-range PCR and Next-generation Sequencing.

Mutations in PIK3CA are associated with overgrowth spectrum disorders including excessive growth in some areas of the body and the central nervous system. Alterations in PIK3CA occur as somatic, postzygotic events and confer a mosaic genotype with variability in phenotypic expression being commonly observed. We describe the second reported prenatal diagnosis of a PIK3CA-related overgrowth spectrum disorder.

Prenatal whole exome sequencing: the views of clinicians, scientists, genetic counsellors and patient representatives.

Objective: Focus groups were conducted with individuals involved in prenatal diagnosis to determine their opinions relating to whole exome sequencing in fetuses with structural anomalies.

Method: Five representatives of patient groups/charities (PRGs) and eight clinical professionals (CPs) participated. Three focus groups occurred (the two groups separately and then combined).

The experience of pregnant women with a diagnosis of fetal lower urinary tract obstruction (LUTO).

Objective: to gain insight into the experiences and perspectives of pregnant women diagnosed antenatally with fetal lower urinary tract obstruction (LUTO) participating in an interventional fetal medicine randomised controlled trial (RCT).

Design: a qualitative study using semi-structured interviews. Interviews were analysed using Riessman's narrative analysis.

"If it helps..." the use of microarray technology in prenatal testing: patient and partners reflections.

The objective was to gain insight into the experiences of women and their partners diagnosed with a fetal abnormality on prenatal ultrasound examination and receiving genetic testing including microarray. Twenty-five semi-structured interviews were performed with women +/- their partners after receiving the results of prenatal genetic testing. Framework analysis was performed to elicit themes and subthemes.