Down Syndrome: Chromosome 21 Gone Awry

What is Down Syndrome?
Named after John Langdon Down, the first physician to identify it, Down syndrome is an equal-opportunity genetic (gene-related) disorder that spans across every race, nationality, and socioeconomic status. It occurs in 1 of every 800 live births and causes mild to severe learning disabilities.

How Does it Happen?
All cells in the human body contain chromosomes, structures that transmit genetic information. Chromosomes consist of thousands of genes that direct the growth and development of the body. All cells contain 23 pairs of chromosomes, in women the pairs are identified as XX and in men as XY. They are numbered 1 through 22.

Down syndrome occurs at the time of conception and is due to an error in cell division. Instead of the normal 46 chromosomes inherited from its parents (23 from each), the newly conceived human has 47. Medical science has pinned down chromosome 21 as the faulty one, but why it happens remains a mystery.

The reproductive cells are the only ones to differentiate from the normal pattern of pairs. The sperm cells of the male and the ovum in females each have 23 individual chromosomes. When the reproductive cells, the sperm and ovum, combine at fertilization, the fertilized egg that results contains 23 chromosome pairs.

When faulty cell division occurs with chromosome number 21, the egg has 3 of the chromosome 21 instead of 2; the extra chromosome is repeated in every cell of the body. This chromosomal pattern is a random error, accounts for 95% of the cases, and is known as Trisomy 21.

In 3%-4% of the cases, part of chromosome 21 breaks off (prior to or at conception) an attaches itself to another chromosome. This is called translocation and may indicate an unusual arrangement of chromosomal material in one of the parents.

In 1%-2% of the cases, the faulty cell division takes place after fertilization, which causes a mixture of two cell types that create a mosaic pattern. Some cells have 47 chromosomes and some have 46. This is called mosaicism.

The common thread of all three Down syndrome types is the extra portion of chromosome 21.

Diagnosis
A chromosome study known as a karyotype provides the definitive confirmation for Down syndrome. Blood or cell tissue is used and the chromosomes are grouped by number, size, and shape.

The initial diagnosis usually comes at or shortly after birth, and is based on physical characteristics associated with the syndrome. These include a flat face, a single crease across the palm of the hand, slanted eyes, weak muscle tone (hypotonia), and loose ligaments (ligament laxity).

Possible Problems
Hypotonia can cause developmental delays. The baby may take longer than other infants to roll over, sit, walk, etc. Ligaments that are too loose cause excessive joint flexibility, which means they are at risk for more dislocations of hips, knees, shoulders, etc.

If there are loose ligaments and weak muscles at the base of the skull/upper part of the spine, the neck bones (vertebrae) may press down on the spinal cord (spinal compression) causing an inability to coordinate muscle movements. This condition is accompanied by a stiff neck, headaches, clumsiness, tripping, weakness, and walking with stiff legs. Any of those symptoms in a child with Down syndrome should be monitored and reported to the doctor.

Early medical care and treatment can address some of these musculoskeletal (muscle and bone related) problems. Surgery, called spinal fusion, is sometimes recommended to hold the bones in the together.

Other Health Issues
Many children with Down syndrome also have other health complications. Statistics show a higher incidence of infection, vision, hearing, thyroid, and respiratory problems. Nearly 40% of the children have congenital heart defects.

Pre-natal Testing
A woman of any number of years can give birth to a baby with Down syndrome, but the risk does go up with age. Screening tests (estimate the risk factor) and diagnostic tests (confirm or deny the diagnosis) are available during pregnancy.

Screening
A blood test is most often used to screen for Down syndrome and is usually done between week 15 and 22 of the pregnancy, with week 15 or 16 being the ideal. A sample is taken and markers are evaluated. The markers are normal substances in the mother’s blood that are secreted by the placenta or fetus. If Down syndrome is present, the levels of these markers will be affected.

In a test known as a triple screen, these markers are checked: unconjugated estriol (uE3), alpha-fetoprotein (AFP), and human chorionic gonadotropin (hCG). If it is a quadruple screen, in addition to the previous three, a marker called inhibin A is evaluated. Which test is given depends on the hospital and the doctor. In Down syndrome pregnancies, the hCG and inhibin A are twice as high as unaffected pregnancies, while the levels of AFP and uE3 tend to be 25%-30% lower.

The age of the fetus and the mother are important in calculating the result. If the gestational age of the fetus is unknown or uncertain, an ultrasound (sonogram) will be given to help determine it. There are other factors that can affect the test results, including diabetes, body weight, multiple gestation (twins, triplets, etc.), and race.

Diagnostic Testing
Because abnormal results can also be the result of other health conditions, the diagnosis is not official until it has been confirmed. The three diagnostic tests currently available are amniocentesis, chorionic villus sampling (CVS), and percutaneous umbilical blood sampling (PUBS).

In an amniocentesis procedure, a small amount of amniotic fluid from the sac surrounding the fetus is drawn out through a needle to be studied. This is performed between week 12 and 20.

Chorionic villus sampling (CVS) is a procedure in which a small piece of chorionic villi (placental tissue) is taken from the uterus to be evaluated. This test is performed with ultra sound guidance and can be done through the abdomen (transabdominal) or cervix (transcervical), depending on the positioning of the placenta. This is test is performed between week 8 and 12.

Percutaneous umbilical blood sampling (PUBS) involves the insertion of a needle into the umbilical cord (tube connecting the fetus to the placenta) to retrieve a sample for observation.

Living Life
Persons with Down syndrome have a life expectancy of approximately 55 years, and many live well beyond that. While they may have more obstacles and challenges to overcome than the average individual, with appropriate medical care most children and adults with this disorder live full and healthy lives.

Just like those of us without Down syndrome, each person is a unique individual with specific needs. Some of them need more help than others. Some have a hard time getting through grade school and some go beyond high school. Some adults can hold jobs and some can’t. But they all have feelings, hopes and dreams, and the need to be loved.

So much of their quality of life depends on not only the medical care they receive, but the love and support of friends and family. Some of these people are the most amazing individuals you will ever have the privilege of meeting. If you don’t believe me, call your local Special Olympics Program and find out when and where the next competition is being held. Then show up. You won’t be disappointed.

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