Presentation: Fetus with raised nuchal translucency

A couple attend their first-trimester dating scan. They have elected to have first-trimester screening for trisomies 21, 18 and 13. During their scan, they are told that the fetus has an increased nuchal translucency (NT) measurement. They have a follow-up consultation with the screening team to discuss their options, and proceed with an appointment with the fetal medicine team.

• Any pregnancy with an NT over 3.5mm should be offered testing for chromosomal anomalies.
• Referral for fetal exome testing can be considered when the NT is over 6.5mm (measured between 11 and 14 weeks) and another anomaly is present (this can include a minor finding) and chromosomal anomalies have not been identified on a normal array CGH.
• When an increased NT is identified in combination with multiple congenital anomalies that are eligible for testing via R21 (see below) even without the nuchal measurement, R21 can be carried out in parallel with chromosome testing.
• If there is a family history of a genetic condition that can cause a raised NT, testing for a known familial variant may be appropriate.

• Refer to local guidance regarding fetal medicine referral.
• Referral to clinical genetics is not routinely indicated for an isolated raised NT. The fetal medicine review will determine whether genomic testing is appropriate, and referral to clinical genetics will typically occur if other anomalies are found, the NT is over 6.5mm, or in cases with a relevant family history of a genetic condition.
• The relevant team will refer to the National Genomic Test Directory to determine which tests are relevant.
• • For information about how to arrange testing in Wales, Scotland or Northern Ireland, see Genomic testing in the devolved nations.
• For a pregnancy with an enlarged NT, there are several relevant test panels. These are outlined below.
• • Where the increased NT is an isolated anomaly:
• • • R22 Fetus with a likely chromosomal abnormality. Unless clinical information and/or initial results indicate otherwise, R22 requests will process both:
• • • • R22.1 Genome-wide common aneuploidy testing; and
• • • • R22.2 Genome-wide microarray.
• • Where the NT is over 6.5mm in combination with another anomaly and a normal R22 result, or there are multiple congenital anomalies:
• • • R21 Fetal anomalies with a likely genetic cause. Unless clinical information and/or initial results indicate otherwise, R21 requests will process:
• • • • R21.1 Genome-wide common aneuploidy testing;
• • • • R21.2 Fetal anomalies whole exome sequencing or large panel sequencing; and
• • • • R21.3 Genome-wide microarray.
• None of the tests outlined above use whole genome sequencing, so you should use your local Genomic Laboratory Hub test order form and consent (record of discussion, or RoD) form.
• Parental samples may be needed for interpretation of the proband’s result. Parental samples can be taken alongside that of the proband, and their DNA stored, or can be requested at a later date if needed.
• For R21 Fetal anomalies with a likely genetic cause, you will need to:
• • ensure that the required multidisciplinary discussions have taken place, including fetal medicine, clinical genetics and the regional specialist R21 laboratory, and that there is an agreement that R21 can be offered;
• • inform your local laboratory of the plan for R21 testing, so that they can arrange the necessary exports to the specialist R21 laboratories in a timely fashion;
• • fill in the R21-specific test order form;
• • take informed consent for both parents, documented on R21-specific RoD forms;
  • send blood samples for both parents to the local laboratory (if only one parent is available, let the lab know – testing can still proceed, but there will be a small reduction in diagnostic yield); and
• • arrange and send a chorionic villus sample or amniocentesis sample for the fetus.
• Note that, in Scotland, referral to clinical genetics is required for consideration of rapid prenatal exome testing.
• All of the above tests are DNA based and require an amniocentesis or chorionic villus sample, or a fetal blood sample in an EDTA (typically purple-topped) tube. For more information about different sample types, see Samples for genomic testing in rare disease.
• If you are discussing genomics concepts with your patients, you may find it helpful to use the visual communication aids for genomics conversations.
• Information about patient eligibility and test indications was correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.

For clinicians

• NHS England: National Genomic Test Directory
• NHS North Thames and NHS West Midlands, Oxford and Wessex Genomic Laboratory Hubs: National Genomic Test Directory Clinical Indication R21 Rapid prenatal exome sequencing test request (PDF, two pages)
• NHS North Thames and NHS West Midlands, Oxford and Wessex Genomic Laboratory Hubs: Record of discussion regarding prenatal exome sequencing (PDF, two pages)
• The Fetal Medicine Foundation: Nuchal translucency at 11–13 weeks of pregnancy (video, two minutes)

For patients

• Oxford University Hospitals NHS Foundation Trust: When a scan shows a nuchal translucency (NT) measurement of 3.5 millimetres or more: Information leaflet (PDF, four pages)
• NHS North Thames and NHS West Midlands, Oxford and Wessex Genomic Laboratory Hubs: Information on prenatal exome sequencing for parents (PDF, two pages)