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) and chronic lung disease beginning in childhood or early adolescence.  The average life expectancy for individuals with CF is presently 35 years.  Although life expectancy has increased as treatment advances have occurred, it remains a serious, chronic disease for those individuals affected.  The condition does not affect intelligence.  Males with CF are infertile.

There are milder forms of CF, one of which causes congenital bilateral absence of the vas deferens (CBAVD) in the absence of lung disease.  Men with CBAVD are azoospermic.  Occasionally an individual with CF has very mild lung disease and few other medical problems.  It is possible that CF variants are responsible for a small proportion of otherwise unexplained chronic pulmonary disease.

CF is inherited as 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 absolutely no manifestations of CF, nor do they have any health problems related to being a CF carrier.  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 testis.

Over 900 variants of the CFTR gene have been identified that result in cystic fibrosis.  Roughly 25 mutations occur frequently enough to be included in a standard panel for carrier testing.  Thus, CF carriers cannot be identified with 100% sensitivity.  Clinical manifestations (phenotype) of CF depend on the specific two CFTR mutations (genotype) in any given individual, although there is also variability in phenotype between individuals with the same genotype.

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

• Individuals with a family history of CF
• Reproductive partners of individuals who have CF
• Couples when one or both partners are Caucasian and are planning a pregnancy or seeking prenatal care
• Carrier testing should be "made available" to non-Caucasian couples

We at The Genetics Center feel that carrier testing should be offered, prior to contemplating pregnancy or as early as possible in a pregnancy, to your patients as follows:  

• Anyone who has a personal and/or family history of CF or whose reproductive partner has a family history of CF

In this situation, we highly recommend referring your patient for genetic consultation prior to conceiving or as early as possible in a newly-recognized pregnancy.

• Any woman who is pregnant to whom prenatal diagnosis for other reasons (such as maternal age or prenatal testing for another genetic disorder) will be recommended

Referring your patient for a genetic consultation in this situation is recommended.

• Anyone who is contemplating carrier screening for other genetic conditions, such as Tay-Sachs disease.

• Either or both members of a Caucasian couple who, when informed of the availability and the limitations of CF carrier screening, have expressed an interest in being tested

We recommend discussing the issue, providing written information (either from one of the laboratories that offer cystic fibrosis carrier testing or a brochure published by ACOG entitled " Cystic Fibrosis Carrier Testing:  The Decision is Yours "), or both.  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 is less than 100% and varies depending on ethnic background.  Sensitivity ranges from less than 60% in Hispanics and Asians to 97% with European-Jewish (Ashkenazi) ancestry.  In addition to the approximately 3% of Caucasians expected to be identified as CF carriers, another 3-5% will have variations of potential genetic significance that might, under certain circumstances, result in a child with mild cystic fibrosis or male infertility.

The following needs to be considered by your patients:

• Whether CF represents a serious enough condition that knowing if a fetus were affected would be important prior to the baby being born

• Whether your patient feels comfortable with some uncertainty about test results and with knowing that prenatal diagnosis is only available when both members of a couple are identified as CF carriers

If one member of a couple is a CF carrier, and the other screens negative, there may be a higher risk for having a child with CF than before screening, but prenatal diagnosis would not be available in this situation.

• What the ethnic backgrounds of both your patient and her partner are

For a couple who are both of European-Jewish ancestry, testing is highly sensitive.  For an Asian couple, not only is the disease much less common than in Caucasians (1/32,000), but carrier testing may detect as few as 1/3 of carriers.  Carrier testing in persons of European ancestry is 85-90% sensitive, and somewhat less sensitive when the ethnic backgrounds include Mediterranean or Southern European.  African-American couples have a 1/15,000 risk for having a child with CF, and carrier testing identifies 70% of carriers.

• Whenever additional prenatal testing or carrier screening is being contemplated for other reasons

For instance, if someone is already planning to have an amniocentesis because of maternal age, carrier testing for CF can be very reasonable, since fetal cells will be available for prenatal diagnosis of CF for "at risk" couples without additional risk to the fetus.

New York State mandates specific informed consent for presymptomatic genetic testing.  The laboratories performing testing have model consents available.  We have a consent for genetic testing that you may prefer to use.  Bear in mind that completion of testing take 1-3 weeks, hence screening both members of a couple may be preferable if your patient is beyond the first trimester.  A genetics referral should be considered if either member of a couple is discovered to be a CF carrier or if other carrier testing is contemplated.  Please review our information on Ashkenazi screening for additional recommendations if your patient and/or her husband are of European-Jewish ancestry.