Presentation: Fetus with ultrasound features suggestive of a chromosomal syndrome

A pregnant woman attends for her 20-week screening scan appointment, having previously declined combined first-trimester screening. The sonographer identifies several fetal anomalies and the couple are referred to a fetal medicine specialist. The specialist confirms that the fetus has a ‘strawberry-shaped’ cranium, choroid plexus cysts, exomphalos and overlapping fingers. A provisional diagnosis of trisomy 18 (Edwards syndrome) is given.

• Testing should be offered if there is a fetal phenotype suggestive of a chromosomal anomaly or syndrome.
• The most common chromosome aneuploidies are, in order of prevalence:
  • trisomy 21 (Down syndrome);
  • trisomy 18 (Edwards syndrome);
  • trisomy 13 (Patau syndrome);
  • 45,X (Turner syndrome); and
  • triploidy.
• If there are fetal ultrasound anomalies that do not appear characteristic of the above common aneuploidies, please refer to one of the following alternative GeNotes articles (depending on the individual case):
  • Pregnant woman with fetal anomalies identified during 20-week screening scan; or
  • Fetus with an isolated congenital anomaly.

• Refer to local guidance regarding fetal medicine and/or clinical genetics referral.
• The relevant team will refer to the National Genomic Test Directory to determine which tests are relevant for the clinical scenario and phenotype.
  • For information about how to arrange testing in Wales, Scotland or Northern Ireland, see Genomic testing in the devolved nations.
• Where there are concerns regarding an atypical phenotype, the following tests may be considered.
  • R22 Fetus with a likely chromosomal abnormality. This will process both:
    • R22.1 Genome-wide common aneuploidy testing; and
    • R22.2 Chromosomal microarray.
• Where there are multiple or complex anomalies and/or above testing is non-diagnostic, rapid fetal exome sequencing may be considered:
  • R21 Fetal anomalies with a likely genetic cause.
• 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
• Gov.uk: 11 physical conditions (20-week scan)
• Gov.uk: 20-week screening scan
• 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)
• Royal College of Obstetricians & Gynaecologists: Amniocentesis and chorionic villus sampling (Green-top Guideline no. 8)
• The Fetal Medicine Foundation: Chromosomal defects

For patients

• Down’s Syndrome Association
• Gov.uk Guidance: Screening in pregnancy: CVS and amniocentesis information for parents
• NHS North Thames and NHS West Midlands, Oxford and Wessex Genomic Laboratory Hubs: Information on prenatal exome sequencing for parents (PDF, two pages)
• SOFT UK
• Turner Syndrome Support Society