Presentation: Patient in 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).
• The National Genomic Test Directory provides full CF carrier testing eligibility criteria, as well as information about who can currently request it (including clinical genetics, fetal medicine and gynaecology services).
• CF carrier testing identifies pathogenic variants responsible for approximately 90% of CF cases. It is important to note that 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.

• In the clinical scenario described, there should be early referral for genomic counselling so that prenatal testing options can be discussed. This will usually be arranged by the midwifery team and should be prioritised to allow prompt review given the time-sensitive nature.
• If a patient presents pre-conceptually with a family history of CF, a referral to clinical genetics for evaluation should be arranged.
• 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.
• For information about how to arrange testing in Wales, Scotland or Northern Ireland, see our dedicated Knowledge Hub resource.
• 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 twenty seconds)

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