Down syndrome: Trisomy 21

What causes Down syndrome?

Down syndrome can be caused by any of three types of abnormal cell division involving chromosome 21.

The three genetic variants include:

Trisomy 21. More than 90% of Down syndrome cases are caused by trisomy 21. The extra chromosome (chromosome 21) results from the development of a sperm or egg. When an egg and sperm combine to form a fertilized egg, there are three (not two) 21 chromosomes present. As cells divide, an extra chromosome is repeated in each cell.
Mosaic trisomy 21. It is a rare form (less than 2% of cases) of Down syndrome. While this is similar to simple trisomy 21, the difference is that an extra chromosome 21 is present in some, but not all human cells. This type of Down syndrome is caused by abnormal cell division after fertilization. The name comes from the random order of normal and abnormal cells. With cellular mosaicism, mixing in different cells of the same type can be observed; whereas in tissue mosaicism one set of cells may have normal chromosomes and another type may have trisomy 21.
Translocation Trisomy 21. Sometimes (in 3-4% of cases) part of chromosome 21 attaches (translocates) to another chromosome (usually chromosome 13, 14 or 15) before or during conception. The carrier (the one who had the translocated chromosome) will have 45 chromosomes instead of 46, but will have all the human genetic material with 46 chromosomes. This is due to the fact that the extra material from chromosome 21 is located on another chromosome (the one that has undergone a translocation). The carrier will have extra material, but will only have one chromosome 21. The carrier will not show any symptoms of Down syndrome because they have the right amount of genetic material.

Couples who have a baby with Down syndrome due to translocation trisomy 21 may be more likely to have Down syndrome in future pregnancies. Indeed, one of the parents can be a balanced translocation carrier.

The probability of a successful translocation depends on the sex of the parent carrying the altered chromosome 21. If the father is the carrier, the risk is about 3%; if the mother is the carrier, the risk is about 12%.

In all cases of trisomy 21, but especially in cases of translocational trisomy 21, it is important that parents receive genetic counseling to determine their risk. There are no known behavioral or environmental causes of Down syndrome.

How dangerous is Down syndrome?

Some parents have a higher risk of having a child with Down syndrome.

Risk factors include:

Mother's age

As the egg ages, a woman's risk of abnormal chromosome division increases. Therefore, the risk of Down syndrome increases with a woman's age.

Mother's age Probability of having a child with Down syndrome

20 1 out of 1600
25 1 out of 1300
30 1 out of 1000
35 1 of 365
40 1 of 90
45 1 of 30

Previous child with Down syndrome

Typically, couples who have had a child with Down syndrome have a slightly increased risk (about 1%) of having a second child with Down syndrome.

A carrier parent

Parents who carry a Down syndrome genetic translocation have an increased risk depending on the type of translocation. Therefore, prenatal screening and genetic counseling are important. People with Down syndrome rarely reproduce. Fifteen to thirty percent of women with Down syndrome are fertile, and the chance of having a child with Down syndrome is approximately 50%.

There is no evidence that a man with Down syndrome had a child. While the incidence of children with Down syndrome increases with maternal age, more children are born to women under the age of 35 due to higher fertility rates. Eighty percent of children with Down syndrome are born to women under the age of 35.

What is the difference between a screening test and a diagnostic test?

A screening test will help identify the possibility of Down syndrome. Screening tests do not give definitive answers, but rather indicate the likelihood that a child has Down syndrome. An abnormal test result does not mean your child has Down syndrome.

The purpose of the screening test is to assess the risk of a child having Down syndrome. If the screening test is positive and there is a risk of Down syndrome, further testing may be recommended. Diagnostic tests can detect Down syndrome before the baby is born.

Experts recommend screening for Down syndrome for all pregnant women during the first trimester.

Diagnostic tests tend to be more expensive and carry some risk; screening tests are performed quickly and easily. However, screening tests are more likely to be erroneous; there are "false positives" (a test shows that a child has a disease when the child does not actually have one) and "false negatives" (a child has a disease but the test shows that he does not). ).

Screening tests during pregnancy

Various screening tests can help determine the possibility of Down syndrome. These screening tests do not give definitive answers, but indicate the likelihood that the child has Down syndrome.

The most common prenatal screening tests include:

Ultrasound
Blood tests. Ultrasound results are consistent with blood tests.
First trimester screening. It is a two-stage screening. Maternal blood is tested for two normal first trimester proteins. Then, with the help of ultrasound, the region of the collar space under the skin behind the child's neck is examined. This test is done between the 11th and 14th week of pregnancy.
Quadruple marker screen. Maternal blood is tested for four substances that typically come from the baby's blood, brain, cerebrospinal fluid, and amniotic fluid. This test is done between the 15th and 20th week of pregnancy.
Triple screening. At the 16th and 18th week of pregnancy, you can take a blood test that measures the amount of three substances: alpha-fetoprotein (AFP) produced by the fetus, human chorionic gonadotropin (hCG) and unconjugated estriol, which is produced by the fetus. produced by the placenta. To determine test results, doctors take into account the mother's age, weight, and ethnicity.

Diagnostic tests during pregnancy

If screening tests are positive or there is a high risk of Down syndrome, additional tests may be needed.

Diagnostic tests that can detect Down syndrome include:

Amniocentesis. performed after 15 weeks.
Chorionic villus sampling. performed between the 9th and 14th weeks.
Percutaneous umbilical blood sampling. performed after the 18th week.

Diagnostic tests for newborns

After birth, the initial diagnosis is usually based on the baby's appearance. If some or all of the characteristic features of Down syndrome are present, the doctor will order a chromosomal karyotype analysis. If an extra chromosome 21 is present, the diagnosis is Down syndrome.

What are the reasons to test or not to test?

Reasons for testing or not testing vary from person to person and couple to couple.

Performing tests and confirming the diagnosis gives you certain options:

Begin planning for a child with special needs
Start addressing anticipated lifestyle changes
Identify support groups and resources

Some individuals or couples may refuse to be tested or additional tested for a number of reasons:

They are satisfied with the results, regardless of the outcome
For personal, moral or religious reasons, the decision to carry a child to term is not an option.

Risk of harm to the developing baby

It is important to carefully discuss the risks and benefits of testing with your doctor. Your doctor will help you decide if the benefits of the results may outweigh the risks of the procedure.

Signs and symptoms of Down syndrome

Down syndrome symptoms can range from mild to severe. Mental and physical development in people with Down syndrome tends to be slower than in people without it. Babies born with Down syndrome may be of average height but grow slowly and remain smaller than other children of the same age.

Some common physical signs of Down syndrome include:

Flat face with an upward slant to the eyes
Short neck
Abnormally shaped ears
Protruding tongue
Small head
Deep crease in the palm of the hand with relatively short fingers
White spots in the iris of the eye
Poor muscle tone, loose ligaments, excessive flexibility
Small hands and feet

People with Down syndrome face a number of common health problems, including:

Congenital heart disease
Hearing problems
Intestinal problems, such as blocked small bowel or esophagus
Celiac disease
Eye problems, such as cataracts
Thyroid dysfunctions
Skeletal problems
Dementia – similar to Alzheimer’s

Treatment

There is no medical treatment for Down syndrome. However, children with Down syndrome will benefit from early medical care and developmental interventions from infancy. Children with Down syndrome can benefit from speech therapy, physical therapy, and occupational therapy. They can get special education and help in school.

Prognosis

The overall health and quality of life of people with Down syndrome has improved significantly in recent years. Many adult patients are healthier, live longer, and are more involved in society through early intervention and therapy.

Coping skills

Finding out that your child has Down syndrome can be scary and difficult. You may not know what to expect and may be worried about caring for a child with a disability.

To deal with this new situation, three actions can be helpful:

Gather a team of professionals. Find a team of doctors, teachers and therapists you trust to work with you to provide the best possible care for your child.
Look for other families. The support of those who have had a similar experience with a child with Down syndrome can be very helpful. These support groups can be found at local hospitals, doctors, schools, and on the Internet.
Don't believe the myths about Down syndrome. In recent years, tremendous progress has been made regarding people with Down syndrome. Most of them live with their families, attend regular schools and work in various jobs as adults. People with Down syndrome can lead full lives.