Carrier Testing for Cystic Fibrosis: Information for Health Professionals

CF is a condition in which, because of an abnormality of a chloride channel gene known as CFTR,  mucous is abnormally viscid.  This results in digestive problems in infancy (due to pancreatic insufficiency) in some individuals, and chronic lung disease beginning in childhood or early adolescence in nearly all affected patients.  The average life expectancy for individuals with CF is presently 35-40 years, and this will probably increase as some promising medications are introduced into clinical practice.  CF does not affect intelligence.  Nearly all men with CF are infertile.

In addition to "classical" CF, there are milder forms of CF, one of which causes congenital bilateral absence of the vas deferens (CBAVD) but no lung disease.  Men with CBAVD are azoospermic.  Rare individuals with CF have very mild lung disease and few other medical problems.  There is speculation that certain CFTR variants may be responsible, at least in part, for a small proportion of otherwise unexplained chronic pulmonary and/or pancreatic disease.

CF is an autosomal recessive disorder.  This means that males and females are equally likely to be affected and that both parents must be carriers of CF to have an affected child.  Carriers have no manifestations of CF, nor do they have any health problems related to being a CF carrier.  Molecular testing is the only way to identify CF carriers.  Approximately 3-4% of the Caucasian population are CF carriers.  When both members of a couple are identified as being CF carriers, each pregnancy has a 25% chance of resulting in a child with CF.  Women with CF have a 50% chance of having an affected child if their partner is a CF carrier.  Some males with CF can have children by in vitro fertilization with spermatogonia aspirated from the testes.

As of 2011, over 1,700 variants of the CFTR gene have been identified that result in cystic fibrosis.  Roughly 23 mutations occur frequently enough to be included in a standard panel for carrier testing (although many laboratories test for more mutations, which very slightly increases the overall sensitivity of carrier screening).

ACOG recommends offering CF carrier testing at preconception counseling, infertility care, or during the first and early second trimester of pregnancy to all patients, with the following considerations:

• A decision to have CF carrier screening should be reached by "informed choice."
• Having a negative screening result reduces, but does not eliminate, the possibility of being a carrier.
• Carrier screening need not be repeated if it has been previously performed.

• Anyone who has a personal and/or family history of CF, or whose reproductive partner has a family history of CF
• Couples where one or both are identified as CF carriers
• A woman's reproductive partner who has CBAVD

We recommend discussing the issue and providing written information (either from one of the laboratories that offer cystic fibrosis carrier testing or a brochure published by ACOG entitled Cystic fibrosis:  prenatal screening and diagnosis).  Please feel free to give your patient a copy of CF: Information for Patients .  It should be emphasized that the ability to detect CF carriers varies considerably with ethnic background.  Sensitivity is less than 50% for Asian Americans, 60-70% for African Americans, ~70% for Hispanics,  ~90% for non-Hispanic Caucasians, and 93-97% for Ashkenazi Jews.

Cystic fibrosis is a component of most pan-ethnic screening panels.  Written informed consent for genetic testing is required by all labs for New York State patients.  If one or both members of a couple are of Ashkenazi Jewish ancestry, please review our information on Ashkenazi screening for further carrier screening recommendations..