Presentation: Woman in pre-conception or early pregnancy with a family history of cystic fibrosis

A 25-year-old woman presents at six weeks pregnant. Her sister’s son has cystic fibrosis, meaning that her sister is almost certainly a carrier. She is anxious and wants to know whether her pregnancy could be affected.

• Those who would be eligible for CF carrier testing in England include:
  • prospective egg or sperm donors;
  • those who have a close relative with CF (up to the fourth degree – for example, a first cousin’s child or a closer relative), in which case you should test the partner whose family is affected;
  • the partner of a known CF carrier;
  • a couple that is closely consanguineous (first cousins) and from an ethnic group with a high carrier frequency; and
  • both parents of a fetus with echogenic bowel (where both parents are available for testing).
• Carrier testing can be requested from primary care and other clinical specialties depending on the clinical scenario and presentation.
• The process for requesting tests may vary locally and regionally; R185 Cystic fibrosis carrier testing is the National Genomic Test Directory’s clinical indication code for CF carrier testing.
• CF carrier testing identifies pathogenic variants responsible for about 90% of CF cases, though it does not exclude all rare variants. For an urgent prenatal test, a two-week turnaround time for results is available.
• If one parent carries a variant, the status of the other partner is needed to determine risk to the pregnancy. This allows for consideration of prenatal testing of the fetus.
• Traditionally, prenatal diagnosis has required invasive testing via either chorionic villus sampling or amniocentesis. Increasingly, non-invasive prenatal diagnosis (NIPD) is used to analyse cell-free placental DNA fragments.

• Understand that CF follows an autosomal recessive inheritance pattern.
• If a woman presents pre-conceptually then they and their partner should be offered CF carrier testing directly from primary care. Presentations within primary care include: having a family history of CF, having a partner who is a known carrier of CF or being from an at-risk group.
• Where the couple is already pregnant, there should be urgent referral as per local pathways (usually clinical genetics or obstetric services) so that carrier testing and prenatal testing options can be discussed and offered in an appropriate timescale. Include details of the affected family member, if the patient is able to give you these.
• Antenatal testing options include chorionic villus sampling, which can be offered from 10 weeks gestation, and NIPD, which can be offered from 9 weeks gestation.
• Explain that the 50 most common variants in White populations (plus the family variant, if available) are tested for as these are responsible for around 90% of cases. A ‘normal’ test result does not exclude the possibility they are a carrier, however. Document this in the patient record.
• 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 containing details of all available tests.
  • For information about how to arrange testing in Wales, Scotland or Northern Ireland, see our dedicated Knowledge Hub resource.
• Follow the local test requesting process; you may be asked for the clinical indication code (R185 Cystic fibrosis carrier testing). Blood samples should be taken in an EDTA tube (typically purple-topped) and sent in the same sample collection service, where your usual provider lab will forward to the genomics laboratory.
• If both expectant parents are found to be CF carriers then refer them to the clinical genetics/genomics service with advice to return if they achieve pregnancy in the meantime.
• CF variant testing is cascaded to appropriate close family members via the clinical genetics clinic, and ‘To whom it may concern’ letters are generated for relatives to hand to their GPs.
• Information about patient eligibility and test indications were 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
• Patient Info: Cystic fibrosis
• Royal College of General Practitioners Communicating Genomics: Autosomal recessive inheritance (video, two minutes)
• NHS South East Genomics: Genetic Test Ordering in Primary Care

References:

• Rohlfs EM, Zhou Z, Heim RA and others. ‘Cystic fibrosis carrier testing in an ethnically diverse US population’. Clinical Chemistry 2011: volume 57, issue 6, pages 841–848. DOI: 10.1373/clinchem.2010.159285

For patients

• Cystic Fibrosis Trust: Testing for cystic fibrosis carriers in families