Cystic Fibrosis Carrier Screening
What is Cystic Fibrosis?
Cystic fibrosis (CF) is a multisystem disease that affects the lungs, pancreas, gastrointestinal tract, and reproductive system. Symptoms of cystic fibrosis can vary among individuals and most frequently include lower airway inflammation and chronic infections that can progress to end-stage lung disease. Pancreatic insufficiency with malabsorption is a complication that occurs in many individuals with CF. Most males with cystic fibrosis experience infertility. Individuals with cystic fibrosis have normal intelligence and the average median survival is currently 37 years. The most common cause of death is respiratory failure. Treatment of an individual with CF can include medication to improve digestion, monitored nutrition, and lung therapy. The life expectancy of people with CF who are born between 2013 and 2017 is predicted to be 44 years. Data also show that of the babies who are born in 2017, half are predicted to live to be 46 years or older.1
How is Cystic Fibrosis Inherited?
Cystic fibrosis is inherited in an autosomal recessive manner. In most cases, both parents must be carriers of the condition in order to have a child with CF. Carriers are not themselves affected by the disease, but have a chance of having a child with the disease. If one parent is found to be a carrier, screening is recommended for their partner. If the partner screens negative, then the couple’s risk of having an affected child is reduced (but not eliminated). If both parents are carriers of CF, there is a 25% chance in each pregnancy of having a child with CF, a 50% chance of having a child who is an unaffected carrier of the condition, and a 25% chance of having a child who is not a carrier and is unaffected.
CF Carrier Screening
Expanded CF Carrier Screen
The expanded CF carrier screen is a panel of 215 variants reported to cause cystic fibrosis. This panel includes the 23 variants recommended for carrier screening by ACOG and ACMG. The remaining variants on the panel have been reported in the literature to be a cause of cystic fibrosis. The CFTR c.1210-12T(5_9) locus (aka IVS8 polyT region 5T, 7T, 9T) is only examined as a reflex to a p.R117H positive result. Improved detection rates are seen in many ethnicities with the use of expanded CF carrier testing.
Expanded rates and residual risks with the expanded CF panel:
| Ethnicity | Carrier Frequency | Detection Rate | Residual Risk |
|---|---|---|---|
| African American | 1/61 | 77% | 1/262 |
| Ashkenazi Jewish | 1/24 | 99% | 1/2301 |
| Asian | 1/94 | 55% | 1/205 |
| Caucasian | 1/25 | 92% | 1/301 |
| Hispanic | 1/58 | 83% | 1/336 |
Cystic Fibrosis Poly T Analysis
When either of our CF panels are ordered, the CFTR c.1210-12T(5_9) locus (aka IVS8 poly-T region 5T, 7T, 9T) is only examined as a reflex to a p.R117H positive result. The 5T poly-T allele is known to play a role in male infertility, even in the absence of p.R117H. If poly-T testing is desired, this can be ordered separately (test code J520) in addition to a CF panel.
Who Should Have Cystic Fibrosis Carrier Screening?
ACMG and ACOG recommend that CF carrier testing be offered to all couples prior to conception or early in pregnancy.
Is There Prenatal Diagnosis for Cystic Fibrosis?
Yes. If both biological parents are found to be carriers of cystic fibrosis, prenatal testing by chorionic villi sampling or amniocentesis can be performed to determine whether or not a fetus is affected.
References
- Cystic Fibrosis Foundation. Understanding Changes in Life Expectancy. https://www.cff.org/Research/Researcher-Resources/Patient-Registry/Understanding-Changes-in-Life-Expectancy/. Accessed September 10, 2019.