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 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 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 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 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: 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.
      • A record of discussion (RoD) form is required for fetal exome sequencing.
  • Where a specific genetic condition is considered likely or there is a relevant family history, further guided genomic testing may 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 RoD 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 (RoD) form, available from your local Genomic Laboratory Hub.
  • 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, chorionic villus sample or fetal blood sample is required in an EDTA tube (typically a purple-topped tube).
• 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

• NHS England: National Genomic Test Directory

For patients

• Great Ormond Street Hospital for Children NHS Foundation Trust: Diaphragmatic hernia information
• Public Health England: Congenital diaphragmatic hernia (CDH) information for parents