Pregnancy genetic testing down syndrome

Down syndrome - Diagnosis and treatment

Diagnosis

The American College of Obstetricians and Gynecologists recommends offering the option of screening tests and diagnostic tests for Down syndrome to all pregnant women, regardless of age.

Screening tests can indicate the likelihood or chances that a mother is carrying a baby with Down syndrome. But these tests can't tell for sure or diagnose whether the baby has Down syndrome.
Diagnostic tests can identify or diagnose whether your baby has Down syndrome.

Your health care provider can discuss the types of tests, advantages and disadvantages, benefits and risks, and the meaning of your results. If appropriate, your provider may recommend that you talk to a genetics counselor.

Screening tests during pregnancy

Screening for Down syndrome is offered as a routine part of prenatal care. Although screening tests can only identify your risk of carrying a baby with Down syndrome, they can help you make decisions about more-specific diagnostic tests.

Screening tests include the first trimester combined test and the integrated screening test.

The first trimester combined test

The first trimester combined test, which is done in two steps, includes:

Blood test. This blood test measures the levels of pregnancy-associated plasma protein-A (PAPP-A) and the pregnancy hormone known as human chorionic gonadotropin (HCG). Abnormal levels of PAPP-A and HCG may indicate a problem with the baby.
Nuchal translucency test. During this test, an ultrasound is used to measure a specific area on the back of your baby's neck. This is known as a nuchal translucency screening test. When abnormalities are present, more fluid than usual tends to collect in this neck tissue.

Using your age and the results of the blood test and the ultrasound, your doctor or genetic counselor can estimate your risk of having a baby with Down syndrome.

Integrated screening test

The integrated screening test is done in two parts during the first and second trimesters of pregnancy. The results are combined to estimate the risk that your baby has Down syndrome.

First trimester. Part one includes a blood test to measure PAPP-A and an ultrasound to measure nuchal translucency.
Second trimester. The quad screen measures your blood level of four pregnancy-associated substances: alpha fetoprotein, estriol, HCG and inhibin A.

Diagnostic tests during pregnancy

If your screening test results are positive or worrisome, or you're at high risk of having a baby with Down syndrome, you might consider more testing to confirm the diagnosis. Your health care provider can help you weigh the pros and cons of these tests.

Diagnostic tests that can identify Down syndrome include:

Chorionic villus sampling (CVS). In CVS, cells are taken from the placenta and used to analyze the fetal chromosomes. This test is typically performed in the first trimester, between 10 and 13 weeks of pregnancy. The risk of pregnancy loss (miscarriage) from a CVS is very low.
Amniocentesis. A sample of the amniotic fluid surrounding the fetus is withdrawn through a needle inserted into the mother's uterus. This sample is then used to analyze the chromosomes of the fetus. Doctors usually perform this test in the second trimester, after 15 weeks of pregnancy. This test also carries a very low risk of miscarriage.

Preimplantation genetic diagnosis is an option for couples undergoing in vitro fertilization who are at increased risk of passing along certain genetic conditions. The embryo is tested for genetic abnormalities before it's implanted in the womb.

Diagnostic tests for newborns

After birth, the initial diagnosis of Down syndrome is often based on the baby's appearance. But the features associated with Down syndrome can be found in babies without Down syndrome, so your health care provider will likely order a test called a chromosomal karyotype to confirm diagnosis. Using a sample of blood, this test analyzes your child's chromosomes. If there's an extra chromosome 21 in all or some cells, the diagnosis is Down syndrome.

More Information

Amniocentesis
Genetic testing
Ultrasound

Treatment

Early intervention for infants and children with Down syndrome can make a major difference in improving their quality of life. Because each child with Down syndrome is unique, treatment will depend on individual needs. Also, different stages of life may require different services.

Team care

If your child has Down syndrome, you'll likely rely on a team of specialists that can provide medical care and help him or her develop skills as fully as possible. Depending on your child's particular needs, your team may include some of these experts:

Primary care pediatrician to coordinate and provide routine childhood care
Pediatric cardiologist
Pediatric gastroenterologist
Pediatric endocrinologist
Developmental pediatrician
Pediatric neurologist
Pediatric ear, nose and throat (ENT) specialist
Pediatric eye doctor (ophthalmologist)
Audiologist
Speech pathologist
Physical therapist
Occupational therapist

You'll need to make important decisions about your child's treatment and education. Build a team of health care providers, teachers and therapists you trust. These professionals can help evaluate the resources in your area and explain state and federal programs for children and adults with disabilities.

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Coping and support

When you learn your child has Down syndrome, you may experience a range of emotions, including anger, fear, worry and sorrow. You may not know what to expect, and you may worry about your ability to care for a child with a disability. The best antidote for fear and worry is information and support.

Consider these steps to prepare yourself and to care for your child:

Ask your health care provider about early intervention programs in your area. Available in most states, these special programs offer infants and young children with Down syndrome stimulation at an early age (typically until age 3) to help develop motor, language, social and self-help skills.
Learn about educational options for school. Depending on your child's needs, that may mean attending regular classes (mainstreaming), special education classes or both. With your health care team's recommendations, work with the school to understand and choose appropriate options.
Seek out other families who are dealing with the same issues. Most communities have support groups for parents of children with Down syndrome. You can also find internet support groups. Family and friends can also be a source of understanding and support.
Participate in social and leisure activities. Take time for family outings and look in your community for social activities such as park district programs, sports teams or ballet classes. Although some adaptations may be required, children and adults with Down syndrome can enjoy social and leisure activities.
Encourage independence. Your child's abilities may be different from other children's abilities, but with your support and some practice your child may be able to perform tasks such as packing lunch, managing hygiene and dressing, and doing light cooking and laundry.
Prepare for the transition to adulthood. Opportunities for living, working, and social and leisure activities can be explored before your child leaves school. Community living or group homes, and community employment, day programs or workshops after high school require some advance planning. Ask about opportunities and support in your area.

Expect a bright future. Most people with Down syndrome live with their families or independently, go to mainstream schools, read and write, participate in the community, and have jobs. People with Down syndrome can live fulfilling lives.

By Mayo Clinic Staff

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Prenatal Testing for Down Syndrome | Patient Education

Down syndrome is a genetic condition caused by extra genes from the 21st chromosome. It results in certain characteristics, including some degree of cognitive disability and other developmental delays. Common physical traits include 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 traits.

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. Under age 25, the odds of having a child with Down syndrome are about 1 in 1,400. At age 35, the odds are about 1 in 350. At age 40, the odds are about 1 in 100.

Causes of Down Syndrome

There are three causes of Down syndrome:

Trisomy 21

An estimated 95 percent of people with Down syndrome have trisomy 21, meaning they have three number 21 chromosomes instead of two. We normally have 23 pairs of chromosomes, each made up of genes. During the formation of the egg and 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 to 97 percent of the extra chromosome is of maternal origin.

Translocation

Translocation occurs in about 3 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 some of the cells but not all of them. The other cells have the usual pair of 21st chromosomes. About 1 to 2 percent of people with Down syndrome have this type.

Prenatal Testing

Screening tests can 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 of miscarriage. We offer options for both screening and diagnostic testing.

Screening Tests

Sequential Integrated Screening — Sequential integrated screening is offered to all pregnant women by the state of California. This non-invasive screening is performed in two steps.

In the first step, which is performed between 10 and 14 weeks of pregnancy, a blood sample is taken from the mother and a nuchal translucency ultrasound is performed to measure the amount of fluid at the back of the baby's neck. If the blood test is scheduled prior to the ultrasound, we can provide the results at the end of the ultrasound appointment. The results of the blood test, the nuchal translucency measurement and the mother's age are used to estimate the risk for Down syndrome and trisomy 18.

The second step is a maternal blood test between 15 to 20 weeks of pregnancy. When the results of this blood test are combined with the results from the first trimester blood test and nuchal translucency ultrasound, the detection rate for Down syndrome increases. This test also provides a personal risk assessment for having a fetus with trisomy 18, Smith-Lemli-Opitz syndrome, an open neural tube defect or an abdominal wall defect.

Diagnostic Tests

Amniocentesis, chorionic villus sampling (CVS) and ultrasound are the three primary procedures for diagnostic testing.

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 involves removing a tiny piece of tissue from the placenta. Under ultrasound guidance, the tissue is obtained either with a needle inserted through the abdomen or a catheter inserted through the cervix. The tissue is then cultured and a karyotype 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 if the mother is carrying multiples. 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.

If You Receive a Positive Result

If you receive 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.

Screening tests for Down syndrome in the first 24 weeks of pregnancy

Relevance
Down's syndrome (also known as Down's disease or Trisomy 21) is an incurable genetic disorder that causes significant physical and mental health problems and disability. However, Down syndrome affects people in completely different ways. Some have significant symptoms, while others have minor health problems and are able to lead relatively normal lives. There is no way to predict how badly a child might be affected. nine0006

Expectant parents during pregnancy are given the opportunity to have a screening test for Down syndrome in their baby to help them make a decision. If a mother is carrying a child with Down syndrome, then a decision should be made whether to terminate the pregnancy or keep it. The information gives parents the opportunity to plan life with a child with Down syndrome.

The most accurate screening tests for Down syndrome include amniotic fluid (amniocentesis) or placental tissue (chorionic villus biopsy (CVS)) to identify abnormal chromosomes associated with Down syndrome. Both of these tests involve inserting a needle into the mother's abdomen, which is known to increase the risk of miscarriage. Thus, screening tests are not suitable for all pregnant women. Therefore, more often take blood and urine tests of the mother, and also conduct an ultrasound examination of the child. These screening tests are not perfect because they can miss cases of Down syndrome and are also at high risk of being positive when the child does not have Down syndrome. Thus, if a high risk is identified using these screening tests, further amniocentesis or CVS is required to confirm the diagnosis of Down syndrome. nine0006

What we did
We analyzed combinations of serum screening tests in the first (up to 14 weeks) and second (up to 24 weeks) trimesters of pregnancy with or without ultrasound screening in the first trimester. Our goal was to identify the most accurate tests for predicting the risk of Down syndrome during pregnancy. One ultrasound index (neckfold thickness) and seven different serological indexes (PAPP-A, total hCG, free beta-hCG, unbound estriol, alpha-fetoprotein, inhibin A, ADAM 12) were studied, which can be used separately, in ratios or in combination with each other, obtained before 24 weeks of gestation, thereby obtaining 32 screening tests for the detection of Down's syndrome. We found 22 studies involving 228615 pregnant women (including 1067 fetuses with Down syndrome). nine0004

What we found
During Down Syndrome screening, which included tests during the first and second trimesters that combined to determine overall risk, we found that a test that included neckfold measurement and PAPP- A in the first trimester, as well as the determination of total hCG, unbound estriol, alpha-fetoprotein and inhibin A in the second trimester, turned out to be the most sensitive, as it allowed to determine 9out of 10 pregnancies associated with Down syndrome. Five percent of pregnant women who were determined to be at high risk on this combination of tests would not have a child with Down syndrome. There have been relatively few studies evaluating these tests, so we cannot draw firm conclusions or recommendations about which test is best.

Other important information to consider
Ultrasounds by themselves have no adverse effects on women, and blood tests can cause discomfort, bruising, and, in rare cases, infection. However, some women who have a high-risk Down syndrome baby on screening and who have had an amniocentesis or CVS are at risk of miscarriage of a non-Down syndrome baby. Parents will need to weigh this risk when deciding whether to perform amniocentesis or CVS after a "high risk" screening test is identified. nine0006

Translation notes:

Translation: Abuzyarova Daria Leonidovna. Editing: Prosyukova Ksenia Olegovna, Yudina Ekaterina Viktorovna. Project coordination for translation into Russian: Cochrane Russia - Cochrane Russia (branch of the Northern Cochrane Center on the basis of Kazan Federal University). For questions related to this translation, please contact us at: [email protected]; [email protected]

Down syndrome - symptoms, risks, early diagnosis

Down syndrome is a genetic disorder caused by abnormal cell division that produces an extra full or partial copy of chromosome 21. This extra genetic material causes the developmental changes and physical features of Down syndrome.

The manifestations of the syndrome vary in severity from person to person, causing lifelong mental retardation and developmental delay. This is the most common genetic chromosomal disorder and is the cause of limited learning ability in children. It also often causes other medical problems, including heart and gastrointestinal problems. nine0006

Unfortunately, a large number of stereotypes and misconceptions about this condition are still widespread in Russia. In addition, not all future parents know what to do in order to identify the risks of this syndrome.

In this article we will describe the main facts about Down syndrome and talk about the possibilities of modern genetic diagnostics, which allow us to detect this syndrome in time.

Down syndrome is one of the most common chromosomal abnormalities. Most of the manifestations of this condition are associated with trisomy - the presence of an additional complete or partial copy - of chromosome 21. This anomaly accounts for up to 90% of cases of Down syndrome.

Interesting fact

Why does chromosome 21 have exactly this serial number

In 1959, when the first conference on the creation of the International System of Human Cytogenetic Nomenclature (ISCN) was held, scientists decided to number the non-sex chromosomes from 1 to 22 in accordance with their decreasing size. So, the smallest chromosome was numbered 22, and the largest - 1. However, at that time, geneticists did not yet have reliable tools for accurately assessing the size of each chromosome, and later it turned out that the 21st chromosome was still smaller than the 22nd. However, several studies have already been published linking the onset of Down syndrome to trisomy 21. To avoid confusion, the numbering was not changed. So chromosome 21 retained its number despite being the smallest. nine0006

Source: Thomas Eggermann and Gesa Schwanitz 2011

The cause of trisomy 21 has not yet been clearly identified. It is generally accepted that it is the result of a spontaneous error, which manifests itself in the inability of the 21st chromosome to separate during the development of an egg or sperm.

Source: National Human Genome Research Institute

In addition to the standard trisomy of chromosome 21, Down syndrome can be caused by its various chromosomal rearrangements: Robertsonian translocations, reciprocal translocations, duplications, submicroscopic aberrations. In rare cases of Down syndrome, mosaicism or mutation of chromosome 21 has been identified. The rarest case of Down syndrome is chromosome 21 tetrasomy - the presence of four free chromosomes 21, or two normal chromosomes and, in addition, isochromosome 21. Aberration usually leads to death in early pregnancy. nine0006

Learn more about the genetics of Down syndrome

Our geneticists have extensive experience in advising on congenital genetic diseases, including Down syndrome. You can sign up for a consultation and get answers to all questions about the genetic causes of this disease, as well as assess the risk of its occurrence in your future children. You can sign up by phone 8 (499) 677-52-22 or via chat.

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Down syndrome - symptoms

In addition to the well-known features of the disease, such as mental retardation and learning difficulties, Down syndrome has more than 80 other phenotypic manifestations, including those that affect the central nervous system, heart, gastrointestinal tract, skeleton, and immune system. The phenotypes associated with Down syndrome vary in both frequency and severity, resulting in a wide range of phenotypic combinations.

Cognitive impairment, hypotonia, and craniofacial features are universal phenotypes, while cardiac anomalies affect only about half of people with Down syndrome. Individual phenotypes similar to those seen in Down syndrome have been documented in individuals without trisomy 21, but the overall higher frequency and severity of these phenotypes in individuals with Down syndrome suggests that trisomy plays an important role in initiating or modifying these features. Although it has been suggested that common mechanisms may be involved in the similar phenotypes seen in people with and without trisomy 21, the overall pathophysiology must be proven for each individual phenotype. nine0006

Source: Roper and Reeves, 2006

People with Down syndrome are at increased risk of congenital heart disease, epilepsy, leukemia, thyroid disease, and various mental disorders. Due to various physiological manifestations of the syndrome, such as growth retardation, low muscle tone, flexible ligaments, short arms, atlantoaxial joint instability, and others, their quality of life is markedly reduced. Most often, they cannot have children, or their children inherit the syndrome. nine0006

15 times more often

Leukemia occurs in children with Down syndrome.

Down syndrome - how to assess the risk?

Down syndrome occurs in about 1 in 660 newborns. At the same time, the risk of giving birth to a child with this syndrome increases with the age of the mother. In 20-year-old mothers, it is less than 0.1% and increases gradually to 3% in mothers aged 45.

0.5% of newborns

On average, this is exactly the frequency of manifestation of Down syndrome in developed countries. However, it should be noted that this risk increases with the age of the mother. nine0006

The age of the mother remains the only factor by which we can assess the risk of having Down's syndrome before conception. Parents of children with this condition are usually healthy, and no behavioral or environmental factors affect the likelihood of having a child with this syndrome.

Various prenatal tests and comprehensive studies are used to assess the risk of Down syndrome after conception. non-invasive prenatal tests remain the most reliable and safest way

Benefits of NIPT

Safe
Informative
Fast
Exactly

The non-invasive prenatal test requires only the pregnant woman's venous blood, which contains small fragments of her own genetic material and fragments of the extracellular fetal DNA of the unborn child. With the help of a unique technology, extracellular fetal DNA is isolated, followed by its sequencing by the NGS method. Thanks to this, we can accurately assess the risks of Down syndrome in the fetus. nine0006

The choice of a non-invasive prenatal test depends on many factors. The main things we pay attention to are the history, the gestational age, whether the pregnancy occurred naturally or after IVF, whether donor cells were used in the IVF cycle, the number of fetuses, the presence of a missing twin, what are the results of other tests, and so on.

Want to choose NIPT?

Our geneticist will review the circumstances of your pregnancy and help you select a non-invasive prenatal test to assess your risk of Down syndrome. We have been doing this for over 8 years and have done thousands of consultations and tens of thousands of studies. nine0006

The possibilities of prenatal diagnosis are much broader than the assessment of the risk of Down syndrome. Modern medical technologies allow the use of a wide range of tools for risk assessment and diagnosis of chromosomal rearrangements, mutations and hereditary diseases.