Dr Esther Dempsey, BSc MBBS MSC MRCPCH, British Heart Foundation Clinical Research Fellow, St George’s University of London presented exciting new data on prenatal exome sequencing at The British Society for Genetic Medicine (BSGM) Annual Conference 2019.
Prenatal exome sequencing is soon to be available throughout England. Diagnostic yield is impacted by patient selection and ranges from 8 to 10% in unselected cohorts and as high as 80% in narrower phenotypes such as skeletal dysplasia.
In a recent study, following a year’s implementation of prenatal exome sequencing in selected cases of fetal anomaly, those with an oedema phenotype were reviewed. Fetal oedema has a poor outcome and has many genetic and non-genetic causes presenting a significant challenge for clinicians to diagnose.
Doubling diagnostic yield
In this study, diagnostic rate was considered in three phenotype categories. The first group had persistent raised nuchal translucency (NT) beyond 16 weeks gestation and normal array and infection screen. A virtual rasopathy gene panel was applied, yielding a diagnosis in 1/3 (33%; LZTR1).
The second group had non-immune hydrops fetalis (NIHF), where fluid had accumulated in 2 or more fetal components but there were no other features; diagnostic rate using a virtual fetal hydrops gene panel was 2/4 (50%; PIEZ01, PTPN11).
The final group had multiple fetal abnormalities and oedema in one or more fetal compartments and a normal array.Here a phenotype specific gene panel+/-a fetal hydrops gene panel was used for assessment of the exome and this resulted in a diagnosis in 5/8 (63%; BICD2, SLC6A9, NIPBL, RAF1and TSC1).
Overall 53% of cases with oedema had a genetic diagnosis following exome sequencing and analysis with Congenica software, compared to 26% in those without. Whilst this is a relatively small dataset obtained over the course of 2018, early indications suggest that these figures are a good reflection of subsequent cases and that fetuses with an oedema phenotype are a good group to target for exome sequencing.
The Fetal Odema and Lymphatic Disorder (FOLD) study is now recruiting for an aetiological study including ultrasound markers, deep phenotyping and genomics.
Rapidly identify the cause of prenatal fetal anomalies
Prenatal genetic diagnosis is a critical but complex clinical challenge to inform decisions during pregnancy and after birth. To support the analysis of ultrasound-detected fetal anomalies faster than ever before, we have developed Congenica Prenatal, a pre-configured application available within our clinical decision support platform, with expert curated and annotated gene panels, enabling you to rapidly identify the molecular cause of fetal anomalies.