Presentation: Fetus with an isolated congenital anomaly

A patient presents at 20 weeks’ gestation for a routine anatomy scan in a low-risk pregnancy. The sonographer detects an apparently isolated congenital anomaly. The remainder of the anatomy scan appears normal. First-trimester screening was low risk and there were no other concerning features.

• Discussion regarding genomic testing is dependent on the anomaly detected.
• Testing should be considered where there is a family history of a genetic condition that is associated with the isolated anomaly seen on the ultrasound.
• Details about genomic testing for specific congenital anomalies can be found in other GeNotes articles. See, for example:
• • fetus with a brain anomaly;
  • coarctation of the aorta; and
  • ventriculomegaly.

• 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. Referrals to clinical genetics are not routinely indicated for a fetal isolated congenital anomaly, however, a referral will be considered at this review.
• 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 the 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.
      • The clinician requesting the test will be required to complete a record of discussion form.
  • Where a specific genetic condition is considered likely, or there is a relevant family history, further guided genomic testing my be recommended.

• For tests that are undertaken using whole genome sequencing (WGS), 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 or 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 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).
  • parental samples should be submitted alongside the child’s sample. This is called trio testing. If this is not possible, such as when testing a child in care or a parent is unavailable for testing, the child may be tested as a singleton.
• For tests that do not include WGS, you will need to:
  • complete a test order form and consent (record of discussion) form, available from your local Genomic Laboratory Hub (GLH).
  • include details of the phenotype in the test order form (refer to HPO terms or the clinical summary) as well as the appropriate panel name(s) with associated R number.
  • 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 all these tests, an amniocentesis or chorionic villus sample or fetal blood sample (in an EDTA tube) is required.
• 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: Fetal abnormalities
• National Congenital Anomaly and Rare Disease Registration Service (Public Health England): Congenital anomaly statistics 2018 (PDF, 43 pages)
• NHS England: National Genomic Test Directory
• World Health Organization: Congenital anomalies

For patients

• Please refer patients to the information relating to the specific anomaly detected, which can be found across GeNotes.