Cystic fibrosis (CF) is the most common inherited disease in most European countries and North America’s white population. Paradoxically though, CF is rather unknown to most people; only the latest years there has been some increased awareness of the disease…
Since 2001, CF prenatal testing is offered to all women of reproductive age as a routine part of obstetric care in the United States. In Europe, the situation is much more heterogeneous: in most countries screening is proposed only to couples at high risk; in the UK and France systematic testing for CF is carried out on newborns, but not on couples without a family history.
In this article I will provide some basic information on cystic fibrosis to help you make your informed decision about prenatal testing…
GETTING TO KNOW CYSTIC FIBROSIS
What is cystic fibrosis?
Cystic fibrosis is an inherited disease, which affects most of the organs of the body, often causing problems with the respiratory and digestive systems. It does not affect a person’s intelligence or appearance. CF generally poses serious risk to a person’s health and shortens life span.
What causes cystic fibrosis?
People have CF because a faulty gene is passed from the parents to the child. Cystic fibrosis is a recessive disorder. That means, both parents must carry the abnormal gene. In that case, there is a 25% (1 in 4) chance the child will have CF, a 50% (1 in 2) chance of the child being a carrier and a 25% (1 in 4) chance he/she will not have the faulty gene. Persons who have one copy of the abnormal gene are called carriers. Almost invariably, carriers will not show no signs of CF.
How common is cystic fibrosis?
About 4% of the population (1 in 25 persons) are CF carriers. CF concerns 1 in approximately 2500 births (USA’s white population, Greece; 1 in 3000 in UK, 1 in 4500 in France).
What are the symptoms of CF?
The symptoms of CF can vary in type and severity. Many people with CF produce a thick, sticky mucus in their bodies. This mucus clogs the lungs and makes it hard to breathe, leading to infection and eventually severe lung damage. It can also affect the digestive organs, making it difficult for the body to absorb food. Most men with CF are infertile.
Is there a cure for CF?
Currently there is no cure for CF. However, through research and improved care, quality and length of life for people with the condition continues to improve. While in the 60’s, a child born with the disease was lucky to live beyond five years, today around half of persons with CF are expected to live past 41 (median survival 37 years), and approximately 15% of individuals with CF have a mild form of the disease with a median survival of 56 years.
TESTING FOR CYSTIC FIBROSIS
What is a carrier testing?
Carrier testing looks at a person’s DNA (genetic material) and tells if that person carries a CF gene mutation (an abnormal gene). The test is taken from cells in a blood sample or from cells that are scraped from inside the mouth.
When can CF carrier testing be done?
Carrier testing can be done when a couple is planning a pregnancy, or during pregnancy (ideally before the 20th week of pregnancy). Initially, only one partner is usually checked. If testing shows that a couple is at high risk, more testing can be done during pregnancy to see whether the fetus has CF.
Should I have prenantal testing?
Having the test to learn if you are a CF carrier is a personal choice and may be influenced by medical, ethical or religious factors. You should carefully consider your options in case of a positive result (see below) and decide accordingly.
How accurate is CF carrier testing?
Cystic fibrosis is caused by mutations in the CF transmembrane regulator (CFTR) gene, located on chromosome 7.
Testing for cystic fibrosis, though, is not straightforward. To date, more than 1700 CF mutations have been identified. Of the laboratory tests available for detection of CF mutations, most of them detect between 20 and 32 mutations. With these tests, about 65-80% of the mutations will be identified.
A more complete analysis of the CFTR gene can be done (by a technique called DNA sequencing); this technique is not appropriate for routine carrier screening because, besides being very expensive, it may yield results that can be difficult to interpret. This type of testing is generally reserved for:
- patients with CF,
- patients with a family history of CF,
- infertile men with a specific abnormality called congenital bilateral absence of the vas deferens, (commonly associated with CF), or
- newborns with a positive newborn screening result.
It is very important that you and your partner understand the sensitivity and limitations of testing, as well as your reproductive options.
UNDERSTANDING THE RESULTS OF CF CARRIER SCREENING TEST
One partner negative: If your test results are negative, the chance that you are a CF carrier is small. There are some rare CF gene defects that the test does not detect. For this reason, you could be told your test result is negative, and you could still be a carrier.
One partner positive: If the test results show that one partner is a carrier, the next step is to test the other partner. Both parents must be CF carriers for the baby to have CF.
If one parent has a negative test result, the chance that the baby will have CF is small. Because the risk is small, if one partner is a carrier but the other has a negative result, no further testing is recommended.
If the father is not available for a carrier test, you may discuss with your doctor to help you decide whether to have prenatal testing of the fetus.
Both partners positive: If both partners are CF carriers, further prenatal testing can be done to see if the baby has CF. As stated before, if two CF carriers have a baby, there is a 25% chance that the baby will have CF, 50% chance the baby will be a carrier, and 25% chance that the baby will not be a CF carrier.
WHEN BOTH PARTNERS ARE POSITIVE…
What prenatal tests can be done to know if the fetus is affected?
Prenatal tests done to detect CF (and other disorders) involve obtaining with a needle some of the fetus’ genetic material and analyzing it to see if it is affected. This can be done around the third month of pregnancy by chorionic villus sampling (CVS) or during the fourth month by amniocentesis. With CVS the genetic material is taken from the placenta, with amniocentesis from the amniotic fluid. You should know that both tests have a small risk of miscarriage.
What are our options if the fetus has CF?
You may decide to:
1. Continue the pregnancy. You may, until the time of delivery, get prepared to live with an affected child, learn more about the disease and eventually discuss with other parents who have a child with CF; or
2. End the pregnancy. Each country has its own laws on pregnancy termination. You should discuss this decision with your doctor.
What are our options when planning a pregnancy?
You may decide to:
1. Have amniocentesis or CVS in each pregnancy,
2. Undergo a technique called preimplantation genetic diagnosis, where you do in vitro fertilization with your own sperm and eggs, and then check the embryos for CF by performing an embryo biopsy (see picture above),
3. Use donor sperm or donor eggs (the donor should be tested for CF carrier status), or
4. Adopt a child.
If you are interested in learning more about cystic fibrosis and prenatal testing, discuss it with your obstetrician–gynecologist, or read more here:
Inserm.fr (French and English)
American College of Obstetricians and Gynecologists (ACOG): Cystic Fibrosis prenatal screening and diagnosis. (For patients)
ACOG Committee Opinion: Update on Carrier Screening for Cystic Fibrosis. December 2005
Best practice guidelines for molecular genetic diagnosis of cystic fibrosis and CFTR-related disorders – updated European recommendations. Eur J Hum Genet. 2009 Jan; 17(1): 51–65.
National Health System (NHS) UK: Cystic Fibrosis
American College of Medical Genetics: Technical Standards and Guidelines for CFTR Mutation Testing. 2006 Edition
Heading: ahealthiermichigan.org; Recessive disorder: cysticfibrosis.org.uk, CF flower lungs: Pinterest.com; CF purple ribbon: etsy.com; PGD: www.imt.ie