R21: Rapid prenatal exome sequencing

Rapid prenatal exome sequencing (R21 in the NHS England National Genomic Test Directory) is undertaken for at-risk pregnancies in which a genomic diagnosis would guide management of the fetus. View the NHS rapid exome sequencing service guide for more information.

At the time of writing, R21 testing can only be requested by a consultant clinical geneticist following discussion with the mother’s local obstetrics team. The testing is undertaken on prenatal samples (chorionic villus or amniotic fluid) and is confined to the evaluation of a nationally agreed panel of genes known to cause disorders that may present prenatally. The R21 test is based on exome sequencing.

R21 testing can be requested when:

• a fetus presents with multiple anomalies affecting multiple systems; and/or
• the presentation is suggestive of an underlying monogenic disorder; and
• a molecular diagnosis may influence the management of the pregnancy or the baby in the immediate neonatal period.

Examples of presentations for which R21 testing may be indicated include a fetus with:

• multiple anomalies in a number of different systems;
• a suspected skeletal dysplasia where intrauterine growth restriction has been excluded;
• large echogenic kidneys and a normal bladder;
• major central nervous system anomalies in which a neural tube defect has been excluded;
• multiple contractures (excluding bilateral isolated talipes);
• a nuchal translucency greater than 6.5 millimetres and at least one additional anomaly and in which the array comparative genomic hybridisation (CGH) is normal; or
• non-immune fetal hydrops (fluid/oedema in at least two compartments detected at or after routine second trimester scan) and a normal array CGH.

R21 testing is undertaken by two of the UK’s Genomic Laboratory Hubs (GLHs): Central and South GLH and North Thames GLH. Before a sample is sent to the designated GLH, all referrals must be:

• reviewed by a local consultant clinical geneticist in consultation with the local obstetric team;
• discussed by the clinical geneticist with the receiving GLH;
• sent to the local or referring GLH, who will forward forms and samples to the receiving GLH;
• accompanied by a completed R21 test request form, including patient details, HPO term and contact details for the clinical geneticist and fetal medicine clinicians; and
• accompanied by a completed record of discussion form.

For clinicians

• NHS Genomic Medicine Service: National Genomic Test Directory Clinical Indication R21 Rapid Prenatal Exome Sequencing Test Request form
• NHS England: Rapid exome sequencing service for fetal anomalies testing (PDF, 19 pages)
• NHS North Thames GLH and West Midlands, Oxford and Wessex GLH: Record of discussion regarding prenatal exome sequencing form (PDF, two pages)