Through simple tests we can now learn answers to important questions about a great variety of risks that are based in genetics. The tests that are available can be helpful in many different categories, from early fetal life to mature life risks for the woman who has concerns about breast and ovarian cancer. We live in an amazing time and scientific breakthroughs in genetics are becoming available. In the future many more will be discovered.
First we will look at how testing can be done as part of Prenatal Care. According to the American Congress of Obstetricians and Gynecologists almost all children in the United States are born healthy. Only 2 or 3 out of 100 newborns have major birth defects. For the majority of these the cause is unknown. However, there are certain birth defects that can be tested before the baby is born. These include Down syndrome, Trisomy 13, Trisomy 18, and open neural tube defects.
The risk of having a baby with a chromosome abnormality, such as Down syndrome, increases with the mother’s age. However, ACOG recommends prenatal testing be offered to all pregnant women, regardless of age.
In our office as part of regular prenatal care we now provide the First Trimester Genetic Screening Test. This test was developed in England about 10 years ago, has become popular in the United States, and is now offered around the world. The First Trimester Genetic Screening Test is a simple finger-stick blood test performed on the pregnant woman, combined with an ultrasound of the fetus between 11 and 14 weeks of gestation. The ultrasound confirms the baby’s gestational age and measures the amount of fluid behind the baby’s neck. Results of the blood test and ultrasound are combined and used by a lab to estimate the risk of Down syndrome, Trisomy 13 and Trisomy 18. About 91% of Down syndrome cases are detected by this safe, reliable testing method. A negative test does not completely exclude the possibility of the baby being affected. If you want to have additional testing, it is available, even if you have a normal screening test result. Further tests that are available including CVS testing and amniocentesis. Each of those is highly accurate, but has a slight risk of complications including miscarriage, and so it is reassuring that the first trimester screening test is so very safe.
If you are screened for chromosome abnormalities in the first trimester, you should also be tested for neural tube defects such as spina bifida in the second trimester. This is accomplished by a serum AFP test, routinely done between 15 and 19 weeks of pregnancy. High levels of AFP in the maternal serum may indicate that the developing fetus has a neural tube disorder. Most of the screening results will be normal. A positive screen occurs in about 5% of cases. If a positive screen occurs we will discuss the possible causes of it. This does not mean that the fetus is affected, as most are not. Further testing is available to help determine if a neural tube defect is actually present. If you decide to have further testing, we usually recommend a genetic specialist for it, where the risks of having further testing are very low and the results are highly accurate.
Generally accepted criteria for population testing (according to ACOG) are that the disease can impair health in the affected person, that there is a high frequency of carriers in the population to be screened, that reliable methods are available, technically valid and are cost-effective, and that the testing is voluntary, with counseling available if needed. Carrier screening in contemporary prenatal care is an excellent example of that. It can predict when a baby may be affected.
Such new tests, available now, offer genetic carrier testing for Cystic fibrosis (CF), Spinal Muscular Atrophy (SMA), and Fragile X syndrome. Cystic fibrosis is the most common lethal autosomal recessive disease in the U.S. One out of every 25 Caucasians with no family history of it is a carrier. The carrier rates are less in other ethnic groups: 1 in 45 Hispanics, 1 in every 65 Black Americans, and 1 in 90 Asians. It affects the respiratory, digestive and reproductive systems. It affects about 1 in 3300 people in the U.S. and causes the body to produce abnormally thick mucus, leading to life threatening infections. It does not affect intelligence. The average life span for an individual with it is 37.
Spinal Muscular Atrophy is the second most common lethal autosomal recessive disease in the U.S. It has a carrier frequency of about 1 in 41 people of all racial backgrounds, or 1 in 35 Caucasians. Every year about 1 in 6000 to 1 in 10000 babies is born with SMA. It is a severe, often fatal genetic disorder in which the muscles which are needed for breathing become progressively weaker and waste away. The most common type causes respiratory failure and death by age 2. There is currently no treatment for it.
Fragile X is the most commonly inherited form of mental impairment. It is found in all racial and ethnic groups. It results from excessive CGG repeats on the FMR 1 gene found on the X chromosome. Fragile X is a disorder that causes mental retardation, autism and hyperactivity. It is found in 1 in 4000 males and 1 in 8000 females. One in every 260 women is a carrier for Fragile X, if they have no family history of mental retardation or autism. If MR or autism is present, the risk is greater.
Tay Sachs Disease is an autosomal recessive genetic disease found in Jewish individuals of Central and Eastern European descent. One in five Jews is a carrier for 1 of 19 severe and preventable genetic diseases. These diseases are autosomal recessive, so a carrier is healthy but at risk of passing on the gene mutation to his or her offspring. It is crucial that if one partner has a positive screening test, that the other partner should be screened as well. All at-risk individuals, including interfaith couples should be screened prior to pregnancy, if possible. A simple blood test is all that is needed to screen for these diseases. If both parents are identified as carriers during pregnancy, there is a 25% chance that the baby could be affected. Further testing to evaluate the risk can be done at 11-13 weeks by CVS or at 16 weeks by amniocentesis.
We are also concerned about the genetic risks for breast and ovarian cancer. Breast and ovarian cancer can run in families. In every family, certain traits are shared and passed on from one generation to the next. Most obvious are physical traits such as eye or hair color, or resemblances that parents and children share. Less obvious are inherited genetic traits that control the tendency to develop specific diseases, such as certain cancers.
Most people don’t realize that about 10% of breast and ovarian cancers are hereditary. They are due to a mutated (altered) gene passed on from parent to child. You don’t actually inherit cancer, but rather a higher risk of developing it over time.
Even if there’s a pattern of breast and or ovarian cancer in your family, cancer doesn’t have to be inevitable. You may benefit from learning more about your own risk. Cancer research shows that early detection along with proactive medical care aimed at prevention can reduce cancer risk and save lives.
You can have an inherited risk if:
you were diagnosed with breast cancer before the age of 50 and or ovarian cancer at any age
you have close family members diagnosed with breast cancer before that age of 50, ovarian cancer at any age, or male breast cancer.
We get two copies of every gene, one from our mother and one from our father. Because we inherit all of our different traits through our parents through a genetic blueprint, if either parent carries a BRCA mutation, we may carry it too. Two specific genes called BRCA1 and BRCA2 play a big part in preventing breast and ovarian cancers. Normally these genes protect us to prevent abnormal growth. When they do not work properly certain groups of cells can grow without control and cancer may occur.
BRAC testing can help determine if you are at risk. Taking a closer look at your family history is the first step toward finding out if your risk is increased. BRAC testing is not like a mammogram or a pap test, which is offered to the general population. It’s specifically for people thought to be at high risk of breast or ovarian cancer, due to family history or due to developing breast cancer at a young age or ovarian cancer at any age. The test is done by getting a small sample of blood and sending it out for analysis. The result comes back in about a week. If negative, it means that your risk is no more than average. If positive, there are many steps that can be taken to minimize risk, including early and more frequent screening, more advanced screening techniques such as MRI, and even medications such as Tamoxifen or Evista that are known to reduce the possibility of getting cancer.
We live in exciting times where scientific advances enable us to know more about the future. Knowing your genetic risks can make your life safer. I’m sure that in the future there will be many more breakthrough advances that will give us a longer, healthier life.