The prenatal exome - a door to prenatal diagnostics?
James S Castleman1, Elizabeth Wall2, Stephanie Allen3
1West Midlands Fetal Medicine Centre, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK.
Expert Review of Molecular Diagnostics
|April 20, 2021
Summary
Prenatal exome sequencing (ES) offers rapid molecular diagnosis for fetal structural anomalies, improving counseling and reproductive options. This genetic testing aids in identifying monogenic causes when standard tests fail, benefiting future pregnancies.
Area of Science:
- Medical Genetics
- Fetal Medicine
- Genomic Medicine
Background:
- Prenatal ultrasound often detects structural anomalies in fetuses.
- Conventional genetic tests like karyotype and chromosomal microarray may not identify the underlying cause.
- Exome sequencing (ES) offers a potential solution for rapid molecular diagnosis.
Purpose of the Study:
- To review the evidence for incorporating exome sequencing into the fetal medicine care pathway.
- To explore the benefits and challenges of ES in ongoing pregnancies.
- To consider perspectives from healthcare professionals and patients regarding ES.
Main Methods:
- Comprehensive search of bibliographic databases.
- Appraisal of existing evidence on exome sequencing in prenatal diagnosis.
- Exploration of clinical and patient perspectives.
Main Results:
- Exome sequencing provides a genetic diagnosis for over 10% of fetuses with ultrasound anomalies and normal conventional tests.
- Diagnostic yield varies by phenotype, ranging from 6% to 80% when cytogenetics are inconclusive.
- ES is most effective in carefully selected cases.
Conclusions:
- Exome sequencing is a valuable tool for diagnosing monogenic causes of fetal structural anomalies.
- Expert oversight and multidisciplinary support are crucial for effective implementation and counseling.
- ES enhances antenatal and neonatal care, decision-making, and reproductive planning.
