Presentation: Fetus with anomalies discovered during the 20-week screening scan

A couple attend their routine 20-week screening scan. The fetus is found to have severe ventriculomegaly, with a posterior horn measurement of 16mm.

• Discussion regarding genomic testing is dependent on the anomaly or anomalies detected.
• Genomic testing should be considered if the anomaly/ies are known to have a potential genetic basis.
• Details about genomic testing for specific congenital anomalies can be found in other GeNotes articles. See, for example:
  • ‘Pregnancy at risk of congenital adrenal hyperplasia‘;
  • ‘Coarctation of the aorta‘; and
  • ‘Ventriculomegaly‘.
• The chance of a genetic diagnosis increases if more than one anomaly is detected.
• If there is a family history of a genetic condition, with an inheritance patten that confers a risk to the pregnancy and an associated anomaly seen on the ultrasound, specific genomic testing for a known familial variant may be most appropriate.

• Consult the National Genomic Test Directory. From here you can access the rare and inherited disease eligibility criteria for information about individual tests and their associated eligibility criteria. You can also access a spreadsheet of all available tests.
  • For information about how to arrange testing in Wales, Scotland or Northern Ireland, see Genomic testing in the devolved nations.
• For information about the genes that are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• Refer to local guidance regarding fetal medicine referral. Further review in a fetal medicine unit is usually warranted.
• A fetal medicine review will determine whether genomic testing is appropriate, and referral to clinical genetics will be considered. Referral to clinical genetics is not routinely indicated for an isolated minor congenital anomaly, but may be recommended where there are multiple and/or complex anomalies.
• The fetal medicine team will decide which testing is most suitable and/or discuss the case with a multidisciplinary team, depending on the specific clinical scenario and the family’s wishes.
• The genomic tests that may be considered include the following.
  • Where there is an isolated anomaly:
    • R22 Fetus with a likely chromosomal abnormality. This will process both:
      • R22.1 Genome-wide common aneuploidy testing; and
      • R22.2 Chromosomal microarray.
  • For multiple congenital anomalies, and for certain significant or complex anomalies, rapid fetal exome sequencing may be considered:
    • R21 Fetal anomalies with a likely genetic cause.
• Where a specific genetic condition is considered likely or there is a relevant family history, further guided genomic testing may be recommended.
• 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 child’s result. Parental samples can be taken alongside that of the child, 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

• Gov.uk Guidance: 20-week screening scan pathway requirements
• NHS England: National Genomic Test Directory
• NHS England: Rapid exome sequencing service for fetal anomalies testing: Frequently asked questions (PDF, five pages)
• 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: Ventriculomegaly

References:

• Navaratnam K and Alfirevic Z (Royal College of Obstetricians and Gynaecologists). ‘Amniocentesis and chorionic villus sampling.’ British Journal of Obstetrics and Gynaecology 2022: volume 129, issue 1, pages e1–e5. DOI: 10.1111/1471-0528.16821

For patients

• Antenatal Results & Choices: Genetic tests in pregnancy
• Gov.uk Guidance: Screening in pregnancy: 20-week screening scan
• Gov.uk Guidance: Screening in pregnancy: CVS and amniocentesis information for parents
• NHS England: If antenatal screening tests find something
• NHS North Thames and NHS West Midlands, Oxford and Wessex Genomic Laboratory Hubs: Information on prenatal exome sequencing for parents (PDF, two pages)