Presentation: Fetus with a brain anomaly

A couple attend their anomaly scan at 19 weeks of pregnancy and are told that there is excess fluid on both sides of their baby’s brain. The baby is diagnosed with moderate ventriculomegaly with a measurement of 14 millimetres. The pregnancy has otherwise been low risk and no associated anomalies can be seen.

• Testing is usually offered in all cases of ventriculomegaly, with or without other associated anomalies.
• The chance of identifying an underlying genetic condition increases with more severe ventriculomegaly and where there are associated anomalies.
• It is important that other causes, such as infection, are excluded.

• 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. A transvaginal scan may be undertaken to provide better views of the brain. MRI assessment will be considered.
• 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 isolated ventriculomegaly, though may be relevant if progressive or associated with other anomalies and fetal exome sequencing (see below) is considered. Other brain anomalies may warrant earlier clinical genetics referral for consideration of detailed genomic testing.
• The fetal medicine team will decide which testing is most suitable for the patient and/or discuss the case with a multi-disciplinary 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 multi-disciplinary discussion is required.
  • 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 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).
  • 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 is required in an EDTA tube (purple-topped tube).
• 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
• International Society of Ultrasound and Gynaecology (ISUOG): Ventriculomegaly
• NHS England: National Genomic Test Directory
• NHS England: The 20-week screening scan

For patients

• Great Ormond Street Hospital for Children NHS Foundation Trust: Ventriculomegaly
• SHINE: Spina bifida and hydrocephalus information