Cystic fibrosis (CF) is a genetic disease that primarily affects the lungs and digestive system, leading to the production of thick, sticky mucus. This abnormal mucus can clog airways, trap bacteria, and obstruct organs like the pancreas, causing breathing difficulties, frequent infections, and problems with nutrient absorption. Understanding the risk factors for cystic fibrosis is important for individuals and families, enabling informed decisions about genetic testing and family planning. This article explores the underlying genetic causes and how they contribute to an individual’s risk.
The Genetic Foundation of Cystic Fibrosis
Cystic fibrosis stems from mutations in a gene called the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. This gene provides instructions for making the CFTR protein, which acts as a channel across cell membranes. The CFTR protein regulates the movement of negatively charged chloride ions and water in and out of cells.
In healthy individuals, the CFTR protein ensures that mucus remains thin and slippery, lubricating and protecting various bodily linings, including those in the lungs and digestive system. When the CFTR gene is mutated, the resulting protein may be faulty, produced in insufficient amounts, or entirely absent. This malfunction prevents proper chloride and water transport, causing mucus to become abnormally thick and sticky.
Over 2,000 mutations in the CFTR gene have been identified. The most common, known as delta F508, leads to a faulty CFTR protein that cannot properly transport ions.
How Cystic Fibrosis is Inherited
Cystic fibrosis is inherited in an autosomal recessive pattern, meaning a child must inherit two mutated copies of the CFTR gene—one from each parent—to develop the condition. If an individual inherits only one mutated CFTR gene and one normal copy, they are considered a “carrier” of cystic fibrosis. Carriers typically do not exhibit symptoms of CF because their single functional gene copy is usually sufficient to produce enough working CFTR protein.
Carriers can pass their mutated gene copy to their children. When both parents are carriers of a CFTR gene mutation, there is a specific probability for each pregnancy:
A 25% chance (1 in 4) that the child will inherit two mutated copies and have CF.
A 50% chance (1 in 2) that the child will inherit one mutated and one normal copy, becoming a carrier themselves.
A 25% chance (1 in 4) that the child will inherit two normal copies and neither have CF nor be a carrier.
This probability applies to each pregnancy independently, regardless of previous children’s genetic status.
Factors Increasing Genetic Risk
An individual’s family history significantly influences their likelihood of being a carrier or having a child with cystic fibrosis. Having a sibling, parent, or other close relative diagnosed with CF directly indicates the presence of CFTR gene mutations within the family, increasing the chance of being a carrier. Even without a known family history of CF, individuals can still be carriers.
Ethnic background is another important factor in assessing genetic risk, as the prevalence of CFTR gene carriers varies across different populations. Cystic fibrosis is most common in individuals of Northern European descent, with approximately 1 in 22 to 1 in 27 Caucasians being a carrier. Carrier rates are also notable in Ashkenazi Jewish populations, with about 1 in 25 individuals being a carrier. While CF occurs in all racial and ethnic groups, it is less common in people of African, Hispanic, Middle Eastern, Native American, or Asian descent, which can sometimes lead to a delayed diagnosis in these populations.
Assessing and Understanding Your Risk
Genetic testing provides actionable information for individuals concerned about their risk of cystic fibrosis. Carrier screening, typically performed through a blood test, is available for prospective parents to determine if they carry a CFTR gene mutation. While over 1,000 CFTR mutations can cause CF, carrier screening panels usually detect the most common mutations, identifying about 85% to 90% of carriers in Caucasian populations. A negative result reduces, but does not entirely eliminate, the small chance of being a carrier of a rare, undetected mutation.
Newborn screening programs, implemented in various regions, identify infants who may be at risk for CF shortly after birth. A positive newborn screen prompts further diagnostic tests, such as a sweat chloride test and additional genetic screening, to confirm or rule out a CF diagnosis. Genetic counseling plays a supportive role, offering individuals and families detailed information about CF inheritance, interpreting test results, and discussing family planning options.