Cystic fibrosis (CFTR gene): carriers, screening and inheritance

In CF the body makes thick, sticky mucus that can clog the airways and the digestive system. The NHS lists lung symptoms such as a cough that does not go away and brings up mucus, wheezing, shortness of breath and frequent sinus and chest infections, and digestive symptoms such as constipation, stomach pain, bloating and large, greasy, hard-to-flush stools. Other signs include slow growth in children, weight loss in adults, swollen fingertips with rounder nails and very salty sweat.

The NHS Genomics Education Programme describes CF as progressive: lung damage builds up over time, with recurrent infections leading to bronchiectasis, and the pancreas often cannot release enough digestive enzymes. Most men are infertile because the vas deferens is missing or blocked, women may have reduced fertility, and diabetes and liver disease can occur. Milder forms may not appear until later in childhood or even adulthood.

The cystic fibrosis transmembrane conductance regulator gene, CFTR, carries the instructions for a channel that moves salt and water across cell surfaces. When both copies are altered the channel does not work properly, and secretions become thick. The NHS Genomics Education Programme says there are many different pathogenic variants in CFTR. Some are common, such as delta F508, others are rare, and some produce severe disease while others give a milder picture. This is why two people with CF can have quite different courses.

The same programme says most new diagnoses in the UK come through the newborn blood spot test, which includes a measure called immunoreactive trypsinogen (IRT); if IRT is above a set cut-off, genomic testing for up to 100 known common CFTR variants is carried out. It cautions that cases are occasionally missed, particularly milder presentations involving rare variants, so CF should still be considered in a child with typical symptoms or born abroad where newborn screening is not offered.

Everyone has two copies of CFTR. A carrier has one working copy and one altered copy and has no symptoms. The NHS explains that a child only gets CF if they inherit an altered gene from both parents, and a child who inherits one altered gene is a carrier who could pass the condition on if their partner also carries one.

The chances do not change from one pregnancy to the next. The NHS Genomics Education Programme says the parents of most affected people are carriers and have a 25% chance of an affected child in each pregnancy, and that unaffected siblings and other close relatives have a high chance of being carriers. Because around 1 in 25 people of European ancestry are carriers, there is a small but significant chance that the partner of a carrier is also a carrier, and the programme says siblings and close relatives should be offered counselling and testing at an appropriate age to inform their own reproductive choices.

The NHS says CF is one of the conditions all babies are checked for with the newborn blood spot test, normally done at 5 days old, and asks parents to tell the person taking the test if anyone in the family has CF. If the screen suggests CF, the baby has a sweat test to measure salt. Older children and adults who may have CF have a blood test followed by a sweat test.

The NHS says a relative of someone with CF or a known carrier can arrange carrier testing, as can a person whose partner has CF or is a known carrier. If either partner is a carrier or has CF, genetic counselling can be requested, through the GP or care team, to discuss options. The NHS Genomics Education Programme adds that where both partners are known carriers, options may include pre-implantation genetic testing and non-invasive prenatal diagnosis.

The NHS says there is currently no cure but there are medicines and supportive treatments. Medicines include CFTR modulators, which reduce the effect of the altered gene on cells in the lungs, medicines to widen the airways or clear mucus, antibiotics for infections and steroids to reduce airway inflammation. Physiotherapy, devices such as inhalers and masks, and dietary support with a high-energy diet and sometimes supplements are all part of care, and a lung transplant is considered for some people whose symptoms are not controlled.

Care is lifelong and is usually delivered by an NHS cystic fibrosis care team in a larger hospital. The NHS advises staying physically active, eating well, washing hands, avoiding smoking and vaping, and considering not meeting other people with CF face to face because of a higher risk of serious infections from one another. The NHS names the Cystic Fibrosis Trust as a charity that provides information and support.