Presentation: Fetus with anomalies discovered during the mid-trimester anomaly scan

A couple attend their routine anomaly scan, having previously declined combined screening in the first trimester with an otherwise normal dating scan. The fetus is found to have severe ventriculomegaly, with a measurement of 16 millimetres.

• Discussion regarding genomic testing is dependent on the anomaly detected.
• Genomic testing should be considered where the anomaly is known to be associated with a genetic cause.
• 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.
• Genomic testing should be considered if there is a family history of a genetic condition that is associated with the isolated anomaly seen on the ultrasound.

• Consult the National Genomic Test Directory. From this directory 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 our dedicated Knowledge Hub resource.
• To find out which genes 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 as further review in a Fetal Medicine Unit is usually warranted.
• The 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 a fetal isolated 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 for the patient and/or discuss the case with a multidisciplinary team, depending on the specific clinical scenario and the patient’s wishes.
• Depending on the clinical scenario, a range of different genomic tests may be considered:
  • Where there is an isolated abnormality:
    • R22 Fetus with a likely chromosomal abnormality. This will process both:
      • R22.1 Genome-wide common aneuploidy testing; and
      • R22.2 Chromosomal microarray.
  • For certain significant or complex anomalies and/or where above testing is non-diagnostic, fetal exome sequencing may be considered:
    • R21 Fetal anomalies with a likely genetic cause: fetal exome sequencing.
      • Referral to clinical genetics and/or multidisciplinary discussion is required.
      • A record of discussion form is required as will be completed by the clinician requesting the test.
  • Where a specific genetic condition is considered likely or there is a relevant family history, further guided genomic testing my be recommended.
• For WGS-based tests, you will need to:
  • complete an NHS GMS test order form with details of the proband and parents. Include details of the phenotype (refer to human phenotype ontology (HPO) terms and the clinical summary) and the appropriate panel name(s) with associated R number (see How to complete a test order form for WGS for support).
  • complete an NHS GMS record of discussion (ROD) form for each person being tested. Note that, if you are undertaking trio testing of an affected child and their parents, you will need three of these forms (see How to complete a record of discussion form for support).
• For tests that do not include WGS, you will need to:
  • complete a test order form and consent (ROD) form, available from your local Genomic Laboratory Hub (GLH); and
  • include details of the phenotype (refer to HPO terms or the clinical summary) as well as the appropriate panel name(s) with associated R number.
• For all these tests, an amniocentesis or chorionic villus sample or fetal blood sample in an EDTA tube (purple-topped tube) is required.
• For many of the tests (particularly whole genome and exome sequencing), parental samples are also needed or are helpful.
• 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

• Fetal Medicine Foundation: Ventriculomegaly
• NHS England: National Genomic Test Directory
• NHS: Rapid exome sequencing service for fetal anomalies testing: FAQs (PDF, five pages)
• Office for Health Improvement and Disparities: 20-week screening scan pathway requirements specification

References:

• Navaratnam K and Alfirevic K (Royal College of Obstetricians and Gynaecologists). ‘Amniocentesis and chorionic villus sampling.’ British Journal of Obstetrics and Gynaecology 2021: volume 129, issue 1, pages e1–e5. DOI: 10.1111/1471-0528.16821

For patients

• Antenatal Results and Choices: Genetic tests in pregnancy
• NHS: If antenatal screening tests find something
• Public Health England: Screening in pregnancy: 20-week screening scan
• Public Health England: Screening in pregnancy: CVS and amniocentesis information for parents