Presentation: Pregnancy at risk of cystic fibrosis

A couple attends their booking appointment and advises the midwife that the mother has a brother with cystic fibrosis (CF). She has been tested and is a known carrier. This was an unplanned pregnancy, so they have not been to the GP or to a clinical genetics team to have her partner tested for carrier status.

• Carrier testing can be considered where there is a family history of CF.
• Where one parent is known to be a carrier of CF, the other parent can have carrier testing to determine the chance of a pregnancy having CF.
• Fetal testing should be discussed in cases in which both partners carry a confirmed pathogenic variant.

• 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.
• Collect a detailed family and personal history from the couple.
• Follow local protocols regarding referral. This is likely to involve:
  • referral to clinical genetics services where there is a family history of CF and/or known carrier status and
  • referral to local screening teams.
• Testing options may include:
  • R185: Cystic fibrosis carrier testing.
    • Reports the commonest pathogenic variants in the Northern European population, not the whole CFTR gene.
    • If a familial variant is known, it is important to notify the testing laboratory to ensure that that variant is analysed during testing.
    • If the test does not detect that the individual is a carrier of CF, a residual risk that they are a carrier will be reported. It is also important to include the individual’s ancestry on the test request form to ensure the accuracy of their residual carrier risk.
  • Non-invasive prenatal diagnosis (NIPD): This test has strict inclusion and exclusion criteria, which can be reviewed in the test directory. NIPD can be performed after nine weeks of pregnancy (confirmed via ultrasound scan). Available tests include:
    • R304 NIPD for cystic fibrosis – haplotype testing. This test is available where both parents are carriers of a confirmed pathogenic variant. DNA must be available for both parents and either and a previously affected foetus (or child’s) DNA sample. Parents must not be consanguineous.
    • R305 NIPD for cystic fibrosis – mutation testing. Where a pregnancy is at risk of CF and the father carries a CFTR pathogenic variant listed in the test eligibility criteria which is different to the maternal variant. R305 testing excludes paternal inheritance.
  • Some families will not fulfil criteria for NIPD. In these cases, invasive testing and a more comprehensive CF panel may be offered. Diagnostic testing in this circumstance requires invasive testing (amniocentesis or chorionic villus sampling).
  • If the patient presents pre-conceptually, pre-implantation genomic testing for monogenic disorders may be available. Referral via clinical genetics is required.
  • For many of the tests, parental samples are also needed or are helpful.
• 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 human phenotype ontology (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 NIPD, a blood sample in a Streck tube (or EDTA tube) is required.
• For invasive tests, an amniocentesis or chorionic villus sample, or fetal blood sample (in an EDTA tube) is required, as well as a sample from the mother to test for maternal cell contamination.
• 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
• West Midlands Regional Genetics Laboratory: NIPD for cystic fibrosis (CF) – R304.1 (PDF, one page)

For patients

• Action Medical Research for Children: Cystic Fibrosis
• Cystic Fibrosis Trust