Presentation: Fetus with a diaphragmatic hernia

A woman attends her routine fetal anomaly scan at 20 weeks. During the scan, the sonographer identifies an anomaly in the chest. The stomach appears to be partially above the diaphragm and the heart appears pushed towards the baby’s right side. The sonographer suspects a congenital diaphragmatic hernia (CDH) and refers the case to antenatal clinic for ongoing management.

• Genomic testing should be considered where a CDH is identified.
• Around 30% of CDH cases have an underlying genetic cause.
• The chance of an underlying genetic cause is increased where there are additional and/or associated anomalies.

• 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.
• The fetal medicine review will determine whether genomic testing is appropriate, and referral to clinical genetics will be considered – though note that referral to clinical genetics is not routinely indicated for a fetal isolated diaphragmatic hernia.
• 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.
• Depending on the clinical scenario, a range of different genomic tests may be considered. These are outlined below.
• • Where there is an isolated anomaly:
• • • R22 Fetus with a likely chromosomal abnormality. Unless clinical information and/or initial results indicate otherwise, R22 requests will process both:
• • • • R22.1 Genome-wide common aneuploidy testing; and
• • • • R22.2 Genome-wide microarray.
• • Where there are multiple or complex anomalies:
• • • R21 Fetal anomalies with a likely genetic cause. Fetal exome sequencing can be offered if the phenotype is as described above. Unless clinical information and/or initial results indicate otherwise, R21 requests will process:
• • • • R21.1 Genome-wide common aneuploidy testing;
• • • • R21.2 Fetal anomalies whole exome sequencing or large panel sequencing; and
• • • • R21.3 Genome-wide microarray.
• 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 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
• 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)

For patients

• Gov.uk Guidance: Congenital diaphragmatic hernia: Information for parents
• Great Ormond Street Hospital for Children NHS Foundation Trust: Diaphragmatic hernia
• NHS North Thames and NHS West Midlands, Oxford and Wessex Genomic Laboratory Hubs: Information on prenatal exome sequencing for parents (PDF, two pages)