Down Syndrome

Signs and Symptoms

Down syndrome is a genetic condition caused by extra genes from the 21st chromosome that result in certain characteristics including some degree of mental retardation, or cognitive disability, and other developmental delays. The incidence of Down syndrome in the United States is about 1 in 1,000 births. There is no association between Down syndrome and culture, ethnic group, socioeconomic status or geographic region.

Age-related Risks

Generally, the chance of having a Down syndrome birth is related to the mother's age. The odds of having a child with Down syndrome at age 35 are about 1 in 350. Under age 25, the odds are about 1 in 1,400. At age 40, the odds are about 1 in 100.

Types of Down Syndrome

There are three types of Down syndrome:

• Trisomy 21 — An estimated 95 percent of people with Down syndrome have Trisomy 21, meaning an individual has three instead of two number 21 chromosomes. We normally have 23 pairs of chromosomes, each made up of genes. During the formation of the egg or the sperm a woman's or a man's pair of chromosomes normally split so that only one chromosome is in each egg or sperm. In Trisomy 21, the 21st chromosome pair does not split and a double-dose goes to the egg or sperm. An estimated 95 percent to 97 percent of the extra chromosome is of maternal origin.

• Translocation — This occurs in about 3 percent to 4 percent of people with Down syndrome. In this type, an extra part of the 21st chromosome gets stuck onto another chromosome. In about half of these situations, one parent carries the extra 21st chromosome material in a "balanced" or hidden form.

• Mosaicism — In mosaicism, the person with Down syndrome has an extra 21st chromosome in only some of the cells but not all of them. The other cells have the usual pair of 21st chromosomes. About 1 percent to 2 percent of people with Down syndrome have this type.

In addition to mental retardation and other developmental delays, some common physical traits are an upward slant of the eyes; flattened bridge of the nose; single, deep crease on the palm of the hand; and decreased muscle tone. A child with Down syndrome, however, may not have all these symptoms.

Typically, parents of Down syndrome babies don't have any symptoms themselves even though they may carry an abnormal gene.

Risk of Recurrence

After the birth of a child with Down syndrome, the risk of having a second child with Down syndrome depends on what caused the condition in the first child. A medical geneticist or genetic counselor should be consulted to get more precise information on the risks. The following are some general guidelines:

• Trisomy 21 — The risk of Down syndrome recurring is either 1 percent to 2 percent or the risk based on the mother's age, whichever is higher.

• Translocation — The risk of Down syndrome recurring depends on if the translocation was inherited or not inherited. If not inherited, the risk is the same as the risk based on the mother's age. If inherited, the risk depends on the type of translocation and the sex of the parent carrying the chromosome abnormality. For the more common "balanced" or hidden translocation, the risk ranges from about 3 percent when the father is the carrier to about 12 percent when the mother is the carrier. If a parent carries a rare "21;21" translocation, the risk for Down syndrome is 100 percent.

• Mosicism — The risk is about the same as risk based on the mother's age.

Diagnosis

Screening can provide important information about potential risks for pregnancy. Screening tests have been designed to identify women at increased risk of having a baby with Down syndrome. These tests have no risks of miscarriage, but can't determine with certainty whether a fetus is affected. Diagnostic tests, on the other hand, are extremely accurate at identifying certain abnormalities in the fetus, but carry a small — generally less than 1 percent risk — risk of miscarriage. We offer options for both screening and diagnostic testing.

Screening

• Expanded AFP Screening — An expanded alpha fetoprotein (AFP) screening is a simple blood test. It is performed between 15 and 20 weeks of pregnancy and is recommended by the state of California for all pregnant women. The blood test result is combined with a woman's age to estimate her own personal risk for carrying a fetus with Down syndrome. The blood test also provides information about the risk of open neural tube defects, abdominal wall defects and trisomy 18. The rate of detection for women under 35 is about 85 percent for neural tube defects, 60 percent for Down syndrome and 60 percent for trisomy 18. The detection rate is higher in women over 35 years of age.

  This is a screening test, which means that if your test result is positive, you have an increased risk of a genetic abnormality. It does not diagnose birth defects, or tell you for certain if your fetus does or does not have a birth defect. Women who have an abnormal expanded AFP or who are going to be 35 at the time of delivery have the option of undergoing chorionic villus sample (CVS) or amniocentesis. These tests can diagnose chromosomal disorders, but not all birth defects, with a high degree of certainty.

  This test is typically performed by your obstetrician. You may be referred to the Prenatal Diagnosis Center for a follow-up examination if the AFP screening indicates a potential risk.

• Nuchal Translucency Screening (NT) — UCSF Medical Center is one of the few centers nationwide to offer nuchal translucency screening (NT) screening, a new, non-invasive test performed early in pregnancy to identify women at increased risk for Down syndrome and other birth defects. NT screening is performed between 11 and 14 weeks of pregnancy. It is offered to women of all ages. The screening is done via a high-resolution ultrasound exam of the nuchal area — a fold of skin at the back of the neck of the fetus. The results are combined with the mother's age to determine an adjusted risk for Down syndrome. The rate of detection for Down syndrome is about 80 percent. Based on the results, a woman has the option of undergoing CVS or amniocentesis for diagnosis.

  NT is a screening test only and cannot determine with certainty if the fetus does or does not have Down syndrome, only if your risk seems to be high or low. While this test has been developed for Down syndrome screening, other chromosomal abnormalities can sometimes be detected. In addition, fetuses with an increased area of nuchal translucency are at risk for other birth defects. An additional ultrasound and fetal echocardiogram, an ultrasound of the fetal heart, can be performed at 18 to 20 weeks of gestation to look for these abnormalities, if indicated.

  If the screening indicates that your fetus is at an increased risk of Down syndrome, a genetic counselor or physician will discuss the specific risk. The counselor also will discuss further diagnostic testing available, including chorionic villus sampling (CVS) or amniocentesis.

Diagnostic tests

• Amniocentesis — Amniocentesis is used most commonly to identify chromosomal problems, such as Down syndrome. When the fetus is known to be at risk, it can detect other genetic diseases like cystic fibrosis, Tay-Sachs disease and sickle cell disease. An amniocentesis procedure for genetic testing is typically performed between 15 and 20 weeks of pregnancy. Under ultrasound guidance, a needle is inserted through the abdomen to remove a small amount of amniotic fluid. The cells from the fluid are then cultured and a karyotype analysis — an analysis of the chromosomal make-up of the cells — is performed. It takes about two weeks to receive the results of the test.

  Amniocentesis detects most chromosomal disorders, such as Down syndrome, with a high degree of accuracy. Testing for other genetic diseases, such as Tay-Sachs disease, is not routinely performed but can be detected through specialized testing if your fetus is known to be at risk. Testing for neural tube defects, such as spina bifida, also can be performed. There is a small risk of miscarriage as a result of amniocentesis — about 1 in 100 or less. Miscarriage rates for procedures performed at UCSF Medical Center are less than 1 in 350.

• Chorionic Villus Sampling (CVS) -- Like amniocentesis, chorionic villus sampling is used most commonly to identify chromosomal problems, such as Down syndrome. It can detect other genetic diseases like cystic fibrosis, Tay-Sachs disease and sickle cell disease in at-risk fetuses. The main advantage of CVS over amniocentesis is that it is done much earlier in pregnancy, at 10 to 12 weeks, rather than 15 to 20 weeks.

  CVS involve removing a tiny piece of tissue from the placenta. Under ultrasound guidance, the tissue is obtained either with a needle through the abdomen or a catheter inserted through the cervix. The tissue is then cultured and a karyotype analysis &mash; analysis of the chromosomal make-up of the cells — is performed. It takes about two weeks to receive the results.

  The advantage of CVS over amniocentesis is that the test is performed much earlier in pregnancy, so results are typically available by the end of the third month. A disadvantage is that spinal cord defects cannot be detected. Expanded alpha fetoprotein (AFP)blood testing or ultrasound can be performed later in the pregnancy to screen for spinal cord defects.

  There is a small risk of miscarriage as a result of CVS -- 1 in 100 or less. Miscarriage rates for procedures performed at UCSF Medical Center are less than 1 in 350.

• Ultrasound -- The primary purpose of ultrasound is to determine the status of a pregnancy -- the due date, size of the fetus and multiple gestations. Ultrasound also can provide some information about possible birth defects in a fetus. All patients at UCSF Medical Center undergo a comprehensive ultrasound examination before any invasive tests are performed. Results of the ultrasound are explained at the time of the visit.

  In some patients, an ultrasound raises concern of a possible abnormality in the fetus. We have extensive experience in performing and interpreting ultrasounds in pregnancy.

Please see our Frequently Asked Questions about choroid plexus cysts discovered during ultrasound.

Treatment

If you have positive results on a screening test, we recommend that you discuss this with your doctor and a genetic counselor. Options for further diagnostic testing will be explained. The decision as to whether to have invasive genetic testing is up to you.

If a diagnostic test finds a genetic abnormality, the significance of such results should be discussed with experts familiar with the condition, including a medical geneticist and a genetic counselor, as well as your own doctor.

Medical geneticists and genetic counselors are available at the UCSF Prenatal Diagnosis Center. Referrals and support information are available for all decisions.