Carrier Screening

When beginning a family, people may wonder who their child will take after - will the baby have my hair? His eyes?  What parents may not think about are genetic variants that they may have, but do not express themselves as a physical feature or a health condition.  Sometimes genetic variants cause a gene not to work properly in our body.  People who have a non-working gene variant with little or no symptoms are called carriers.  It is estimated that each person carries one or two genetic variants that can cause a health condition in a child.¹

Humans have approximately 20,000 genes and these genes come in pairs.  A child may be born with a genetic condition when they inherit a non-working variant in the same gene from both parents.  These conditions are called recessive conditions.  To determine if a pregnancy may be at an increased risk to have a recessive condition, carrier screening is available.

Standard Carrier Testing Recommendations:

Some recessive conditions are more common than others.  Based on the high carrier frequencies of cystic fibrosis, spinal muscular atrophy, and hemoglobinopathies, the American College of Obstetrics and Gynecology recommends that all pregnant women and/or couples considering pregnancy should be offered carrier screening.²

Carrier screening is usually performed using a blood or saliva sample.  Following please find information on the most commonly screened conditions:

Cystic Fibrosis (CF) ^{3 4}

• Causes thick mucus to build up in the lungs which can lead to frequent infections
• Over time, the lungs can become damaged and breathing becomes difficult
• Thick mucus can also cause digestive problems
• The average lifespan for someone with CF is 42 years

Spinal Muscular Atrophy (SMA) ^2 5

• Causes the muscles to weaken over time
• The most common form of SMA causes overall muscle weakness before 6 months old and death by 2-4 years old from respiratory failure
• In other forms of SMA, muscle weakness can develop before birth or later in childhood

Hemoglobinopathies ^{2 5 6 7 8}

• Cause anemias, such as sickle cell anemia and thalassemia
• Symptoms of these conditions are fatigue, yellow skin and eyes, frequent infections, swelling and pain in the joints, and organ damage
• Lifespan can be shortened

What is the chance you are a carrier if you do not have a family history of these conditions? (Note: these are estimates)

Expanded Carrier Screening:

People who want more comprehensive information about their carrier status may opt for expanded carrier screening.  Expanded carrier screening provides information on carrier status for more than 100 conditions.  Conditions included in expanded carrier screening should:

• Be fairly common, meaning the chance for a patient to be a carrier is 1% or greater
• Have a significant effect on the quality of life either cognitively, physically, or both
• Have an early onset. Prenatal carrier testing is not intended for adult onset conditions
• Benefit from early detection and treatment
• Be conditions that can be prenatally diagnosed ²

Results of Carrier Screening:

As with other types of screening tests, it is important to recognize the limitations of carrier screening. Carrier screening may not detect all carriers of a condition, but a negative carrier screening result reduces the likelihood of being a carrier. ¹For example, if a non-Hispanic White individual screens negative for cystic fibrosis, there is still a 1 in 343 chance that this individual is a carrier of cystic fibrosis. This is because carrier screening may be unable to detect variants less commonly associated with a particular condition. Sometimes the exact residual risk of being a carrier following screening is unknown.

If someone is found to be a carrier of a genetic condition, it does not mean that his or her children will have that condition.   However, if both parents are carriers for the same condition, then there is a 1 in 4 or 25% chance of an affected child and a 75% chance of an unaffected child.  If the other partner is tested and screens negative, then the chance of an affected child is significantly reduced. 

Next Steps for Carriers:

When a person is found to be a carrier of a genetic condition, recommended next steps include offering carrier screening to his/her partner and referral to a genetic counselor.  Genetic counseling should include a discussion of the specific condition, reproductive risks, prenatal diagnosis, and options for future pregnancy including adoption, donor egg or sperm, and preimplantation genetic diagnosis. Carriers are also encouraged to inform their family members who are at risk to be carriers so they can pursue screening if desired.²

References

^{1. Gao Z., Waggoner D., Stephens M., Ober C., Przeworski M., 2015 An estimate of the average number of recessive lethal mutations carried by humans. Genetics 199: 1243–1254.} 

^{2. Carrier screening in the age of genomic medicine. Committee Opinion No. 690. American College of Obstetricians and Gynecologists. Obstet Gynecol 2017;129:e35–40.} 

^{3. Ong T, Marshall SG, Karczeski BA, et al. Cystic Fibrosis and Congenital Absence of the Vas Deferens. 2001 Mar 26 [Updated 2017 Feb 2]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from:}
https://www.ncbi.nlm.nih.gov/books/NBK1250/

^{4. Carrier screening for genetic conditions. Committee Opinion No. 691. American College of Obstetricians and Gynecologists. Obstet Gynecol 2017;129:e41–55.}

^{5. Prior TW, Finanger E. Spinal Muscular Atrophy. 2000 Feb 24 [Updated 2016 Dec 22]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from:} 
https://www.ncbi.nlm.nih.gov/books/NBK1352/

^{6. Origa R, Moi P. Alpha-Thalassemia. 2005 Nov 1 [Updated 2016 Dec 29]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from:}
https://www.ncbi.nlm.nih.gov/books/NBK1435/

^{7. Origa R. Beta-Thalassemia. 2000 Sep 28 [Updated 2015 May 14]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from:}
https://www.ncbi.nlm.nih.gov/books/NBK1426/

^{8. Bender MA, Douthitt Seibel G. Sickle Cell Disease. 2003 Sep 15 [Updated 2014 Oct 23]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from:} 
https://www.ncbi.nlm.nih.gov/books/NBK1377/

This article was written by Maria Keever, MMSc, CGC, certified genetic counselor with WakeMed Physician Practices - Maternal Fetal Medicine.