Genetic Carrier Screening
What is genetic carrier screening and why is it part of your infertility work-up?
Carrier screening is a blood test performed to determine if you are a carrier for common genetic diseases that can be inherited. Most individuals are silent carriers, which means they only have one copy of the mutation within a gene, allowing the gene to function properly. By performing genetic carrier screening before pregnancy, it allows you to prepare for possible pregnancy risks and enables you to learn about your reproductive options.
According to the American College of Obstetrics & Gynecology (ACOG) and the American College of Medical Genetics and Genomics (ACMG) the recommendations for testing specific conditions includes the following:
Cystic fibrosis (CF) is a life-threatening, multiorgan disease that affects the lungs, pancreas, gastrointestinal tract and reproductive tract. CF is caused by a mutation in the CFTR gene. According to the Cystic Fibrosis Foundation, the current median age of survival is 42. This disease is most common amongst the white population. As a result, sensitivity of screening can vary across differing populations. There are hundreds of known variants, however screening only includes the most common ones. This means that after screening, there is still a small residual risk of being a carrier.
Spinal Muscular Atrophy (SMA)
SMA is an autosomal recessive disease in the gene SMN1 that causes degeneration of the spinal cord motor nerves. Individuals affect do not produce enough protein called survival motor neuron (SMN) causing motor neurons to die. This leads to severe muscle weakness that can cause paralysis and death. Carrier frequency in the general population is 1/40-1/60, however can vary by ethnicity. For examples, Ashkenazi Jews have a higher risk of being carriers compared to the Hispanic population who have a lower carrier frequency. To date, there is no treatment for SMA.
Sickle Cell Anemia
Sickle cell anemia is an autosomal recessive disorder that causes an abnormal hemoglobin shape. Hemoglobin is a protein that is responsible for carrying oxygen for the body’s tissue and returns carbon dioxide back to the lungs. Carriers are said to have sickle cell trait and may have mild symptoms of anemia. Sickle cell disease is more severe and can result in occlusion in the blood vessels (vasoocclusive crisis) causing interruption of blood supply to organs. This results from acute illness, decreased oxygenation and stress. Repeat vasoocclusive crisis long term, can result in organ failure. These crises are often very painful and requires hospitalization. Sickle cell anemia results from having two copies of a single amino acid change in the -globin gene from glutamate to valine in the number 6 position of the protein. Approximately 1/10 African Americans have sickle cell trait.
Fragile X Syndrome
Fragile X syndrome is the most common form of inherited intellectual disability and autism, which can vary in severity. Fragile X is an x-linked inherited disorder that primarily affects males, caused by an expansion of trinucleotide repeat in DNA, cytosine-guanine-guanine (CGG) on the FMR1 gene. The normal number of repeats is 5-44, and 55-200 repeats is considered a pre-mutation. A person with 55-200 repeats does not have features of Fragile X syndrome but is at higher risk of developing a tremor/ataxia. In women, the pre-mutation may present as primary ovarian insufficiency (previously, premature ovarian failure). When greater than 200 repeats are present, this is considered a full mutation causing the FMR1 gene to become inactive and causes Fragile X syndrome.
What happens if I am a carrier?
The next step involves testing your partner for variants in the same gene. If your partner is negative, then the risk of having an affected child is significantly reduced (but not zero). If you and your partner are both carrier for the same genetic disease then your risk of having an affected child is approximately 25%. Speaking with a genetic counselor will be important to help in making informed decisions on how to proceed. You have the option to undergo IVF with preimplantation genetic testing of single gene disorders (PGT-M) in order to reduce the risk of having an affected child.