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.

• Parental testing can be considered where there is a family history of CF.
• Fetal testing should be discussed in cases in which both partners carry a confirmed pathogenic variant.

• Collect a detailed family and personal history from the couple.
• Follow local protocols regarding referral. This is likely to involve:
  • referral to clinical genetics of cases in which there is a family history of cystic fibrosis and/or known carrier status; and
  • referral to local screening teams.
• The clinical genetics team will review the NHS England National Genomic Test Directory eligibility criteria to determine which tests are available to your patients. The directory itself provides a list of all available tests.
  • For those working within NHS Wales, please consult the All Wales Medical Genomics Service website for information on how to arrange testing.
• Testing options may include:
  • R185: Cystic fibrosis carrier testing. This is likely to be the primary test undertaken in cases in which a familial diagnosis has been made. This test will report on the most common pathogenic variants in the Northern European population, not on the whole CFTR gene. If the specific 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. Some of the available tests are:
    • R304 NIPD for cystic fibrosis – haplotype testing. This can be used if it has been confirmed that both parents are carriers of a confirmed pathogenic variant and an unaffected or unaffected non-carrier pregnancy or child’s sample is available. Parents must not be consanguineous. This can be performed after nine weeks of pregnancy (confirmed via ultrasound scan).
    • R305 NIPD for cystic fibrosis – mutation testing. This is used for pregnancies at risk of CF where the father carries a CFTR pathogenic variant listed in the test eligibility criteria and both parents are confirmed to be carriers of a different mutation. It can be performed after nine weeks of pregnancy (confirmed via ultrasound scan). R305 testing excludes paternal inheritance.
      • Diagnostic testing in this circumstance requires invasive testing (amniocentesis or chorionic villus sampling).
    • Some families will not fulfil criteria for NIPD. In these cases, invasive testing and a more comprehensive CF panel may be offered.
    • If the patient presents pre-conceptually, pre-implantation genomic testing for monogenic disorders may be available. Referral via clinical genetics is required.
• For NIPD, a blood sample in a Streck tube (or EDTA tube) is required. For many of the tests, parental samples are also needed or are helpful. Please refer to your local Genomic Laboratory Hub (GLH) for details of test request forms and where to send samples.
• 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. For many of the tests, parental samples are also needed or are helpful. Please refer to your local GLH for details of test request forms and where to send samples.
• A record of discussion form, or another appropriate local consent form, is required for testing.
• 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

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