Fallot tetralogy

Definition

Down syndrome is the most common cause of mental retardation and malformation in a newborn. It occurs because of the presence of an extra chromosome.

Description

Chromosomes are the units of genetic information that exist within every cell of the body. Twenty-three distinctive pairs, or 46 total chromosomes, are located within the nucleus (central structure) of each cell. When a baby is conceived by the combining of one sperm cell with one egg cell, the baby receives 23 chromosomes from each parent, for a total of 46 chromosomes. Sometimes, an accident in the production of a sperm or egg cell causes that cell to contain 24 chromosomes. This event is referred to as nondisjunction. When this defective cell is involved in the conception of a baby, that baby will have a total of 47 chromosomes. The extra chromosome in Down syndrome is labeled number 21. For this reason, the existence of three such chromosomes is sometimes referred to as Trisomy 21.

In a very rare number of Down syndrome cases (about 1-2%), the original egg and sperm cells are completely normal. The problem occurs sometime shortly after fertilization; during the phase where cells are dividing rapidly. One cell divides abnormally, creating a line of cells with an extra chromosome 21. This form of genetic disorder is called a mosaic. The individual with this type of Down syndrome has two types of cells: those with 46 chromosomes (the normal number), and those with 47 chromosomes (as occurs in Down syndrome). Some researchers have suggested that individuals with this type of mosaic form of Down syndrome have less severe signs and symptoms of the disorder.

Another relatively rare genetic accident which can cause Down syndrome is called translocation. During cell division, the number 21 chromosome somehow breaks. A piece of the 21 chromosome then becomes attached to another chromosome. Each cell still has 46 chromosomes, but the extra piece of chromosome 21 results in the signs and symptoms of Down syndrome. Translocations occur in about 3-4% of cases of Down syndrome.

Down syndrome occurs in about 1 in every 800-1,000 births. It affects an equal number of boy and girl babies. Less than 25% of Down syndrome cases occur due to an extra chromosome in the sperm cell. The majority of cases of Down syndrome occur due to an extra chromosome 21 within the egg cell supplied by the mother (nondisjunction). As a woman's age (maternal age) increases, the risk of having a Down syndrome baby increases significantly. For example, at younger ages, the risk is about one in 4,000. By the time the woman is age 35, the risk increases to one in 400; by age 40 the risk increases to one in 110; and by age 45 the risk becomes one in 35. There is no increased risk of either mosaicism or translocation with increased maternal age.

Causes and symptoms

While Down syndrome is a chromosomal disorder, a baby is usually identified at birth through observation of a set of common physical characteristics. Babies with Down syndrome tend to be overly quiet, less responsive, with weak, floppy muscles. Furthermore, a number of physical signs may be present. These include:

• Flat appearing face
• Small head
• Flat bridge of the nose
• Smaller than normal, low-set nose
• Small mouth, which causes the tongue to stick out and to appear overly large
• Upward slanting eyes
• Extra folds of skin located at the inside corner of each eye, near the nose (called epicanthal folds)
• Rounded cheeks
• Small, misshapen ears
• Small, wide hands
• An unusual, deep crease across the center of the palm (called a simian crease)
• A malformed fifth finger
• A wide space between the big and the second toes
• Unusual creases on the soles of the feet
• Overly-flexible joints (sometimes referred to as being double-jointed)
• Shorter than normal height.

Other types of defects often accompany Down syndrome. About 30-50% of all children with Down syndrome are found to have heart defects. A number of different heart defects are common in Down syndrome, including abnormal openings (holes) in the walls which separate the heart's chambers (atrial septal defect, ventricular septal defect). These result in abnormal patterns of blood flow within the heart. The abnormal blood flow often means that less oxygen is sent into circulation throughout the body. Another heart defect which occurs in Down syndrome is called Tetralogy of Fallot. Tetralogy of Fallot consists of a hole in the heart, along with three other major heart defects.

Malformations of the gastrointestinal tract are present in about 5-7% of children with Down syndrome. The most common malformation is a narrowed, obstructed duodenum (the part of the intestine into which the stomach empties). This disorder, called duodenal atresia, interferes with the baby's milk or formula leaving the stomach and entering the intestine for digestion. The baby often vomits forcibly after feeding, and cannot gain weight appropriately until the defect is repaired.

Other medical conditions which occur in patients with Down syndrome include an increased chance of developing infections, especially ear infections and pneumonia; certain kidney disorders; thyroid disease (especially low or hypothyroid); hearing loss; vision impairment requiring glasses (corrective lenses); and a 20-times greater chance of developing leukemia.

Development in a baby and child with Down syndrome occurs at a much slower than normal rate. Because of weak, floppy muscles (hypotonia), babies learn to sit up, crawl, and walk much later than their normal peers. Talking is also quite delayed. The level of mental retardation is considered to be mild-to-moderate in Down syndrome. The actual IQ range of Down syndrome children is quite varied, but the majority of such children are in what is sometimes known as the trainable range. This means that most people with Down syndrome can be trained to do regular self-care tasks, function in a socially appropriate manner in a normal home environment, and even hold simple jobs.

As people with Down syndrome age, they face an increased chance of developing the brain disease called Alzheimer's (sometimes referred to as dementia or senility). Most people have a 6 in 100 risk of developing Alzheimer's, but people with Down syndrome have a 25 in 100 chance of the disease. Alzheimer's disease causes the brain to shrink and to break down. The number of brain cells decreases, and abnormal deposits and structural arrangements occur. This process results in a loss of brain functioning. People with Alzheimer's have strikingly faulty memories. Over time, people with Alzheimer's disease will lapse into an increasingly unresponsive state. Some researchers have shown that even Down syndrome patients who do not appear to have Alzheimer's disease have the same changes occurring to the structures and cells of their brains.

As people with Down syndrome age, they also have an increased chance of developing a number of other illnesses, including cataracts, thyroid problems, diabetes, and seizure disorders.

Diagnosis

Diagnosis is usually suspected at birth, when the characteristic physical signs of Down syndrome are noted. Once this suspicion has been raised, genetic testing (chromosome analysis) can be undertaken in order to verify the presence of the disorder. This testing is usually done on a blood sample, although chromosome analysis can also be done on other types of tissue, including skin. The cells to be studied are prepared in a laboratory. Chemical stain is added to make the characteristics of the cells and the chromosomes stand out. Chemicals are added to prompt the cells to go through normal development, up to the point where the chromosomes are most visible, prior to cell division. At this point, they are examined under a microscope and photographed. The photograph is used to sort the different sizes and shapes of chromosomes into pairs. In most cases of Down syndrome, one extra chromosome 21 will be revealed. The final result of such testing, with the photographed chromosomes paired and organized by shape and size, is called the individual's karyotype.

Treatment

No treatment is available to cure Down syndrome. Treatment is directed at addressing the individual concerns of a particular patient. For example, heart defects will many times require surgical repair, as will duodenal atresia. Many Down syndrome patients will need to wear glasses to correct vision. Patients with hearing impairment benefit from hearing aids.

While some decades ago, all Down syndrome children were quickly placed into institutions for lifelong care, research shows very clearly that the best outlook for children with Down syndrome is a normal family life in their own home. This requires careful support and education of the parents and the siblings. It is a life-changing event to learn that a new baby has a permanent condition which will effect essentially all aspects of his or her development. Some community groups exist to help families deal with the emotional effects of this new information, and to help plan for the baby's future. Schools are required to provide services for children with Down syndrome, sometimes in separate special education classrooms, and sometimes in regular classrooms (this is called mainstreaming or inclusion).

Prognosis

The prognosis in Down syndrome is quite variable, depending on the types of complications (heart defects, susceptibility to infections, development of leukemia) of each individual baby. The severity of the retardation can also vary significantly. Without the presence of heart defects, about 90% of children with Down syndrome live into their teens. People with Down syndrome appear to go through the normal physical changes of aging more rapidly, however. The average age of death for an individual with Down syndrome is about 50-55 years.

Still, the prognosis for a baby born with Down syndrome is better than ever before. Because of modern medical treatments, including antibiotics to treat infections, and surgery to treat heart defects and duodenal atresia, life expectancy has greatly increased. Community and family support allows people with Down syndrome to have rich, meaningful relationships. Because of educational programs, some people with Down syndrome are able to hold jobs.

Men with Down syndrome appear to be uniformly sterile (meaning that they are unable to have offspring). Women with Down syndrome, however, are fully capable of having babies. About 50% of these babies, however, will also be born with Down syndrome.

Prevention

Efforts at prevention of Down syndrome are aimed at genetic counseling of couples who are preparing to have babies. A counselor needs to inform a woman that her risk of having a baby with Down syndrome increases with her increasing age. Two types of testing is available during a pregnancy, to determine if the baby being carried has Down syndrome.

Screening tests are used to estimate the chance that an individual woman will have a baby with Down syndrome. At 14-17 weeks of pregnancy, measurements of a substance called AFP (alpha-fetoprotein) can be performed. AFP is normally found circulating in the blood of a pregnant woman, but may be unusually high or low with certain disorders. Carrying a baby with Down syndrome often causes AFP to be lower than normal. This information alone, or along with measurements of two other hormones, is considered along with the mother's age to calculate the risk of the baby being born with Down syndrome. These results are only predictions, and are only correct about 60% of the time.

The only way to definitively establish (with about 98-99% accuracy) the presence or absence of Down syndrome in a developing baby, is to test tissue from the pregnancy itself. This is usually done either by amniocentesis, or chorionic villus sampling (CVS). In amniocentesis, a small amount of the fluid in which the baby is floating is withdrawn with a long, thin needle. In chorionic villus sampling, a tiny tube is inserted into the opening of the uterus to retrieve a small sample of the placenta (the organ which attaches the growing baby to the mother via the umbilical cord, and provides oxygen and nutrition). Both amniocentesis and CVS allow the baby's own karyotype to be determined. A couple must then decide whether to use this information in order to begin to prepare for the arrival of a baby with Down syndrome, or to terminate the pregnancy.

Once a couple has had one baby with Down syndrome, they are often concerned about the likelihood of future offspring also being born with the disorder. Most research indicates that this chance remains the same as for any woman at a similar age. However, when the baby with Down syndrome has the type that results from a translocation, it is possible that one of the two parents is a carrier of that defect. A carrier "carries" the genetic defect, but does not actually have the disorder. When one parent is a carrier of a translocation, the chance of future offspring having Down syndrome is greatly increased. The specific risk will have to be calculated by a genetic counselor.

Key Terms

Chromosome

The structures which carry genetic information. Chromosomes are located within every cell, and are responsible for directing the development and functioning of all the cells in the body. The normal number is 46 (23 pairs).

Karyotype

The specific chromosomal makeup of a particular cell.

Mental retardation

A condition where an individual has a lower-than-normal IQ, and thus is developmentally delayed.

Mosaic

A term referring to a genetic situation, in which an individual's cells do not have the exact same composition of chromosomes. In Down syndrome, this may mean that some of the individual's cells have a normal 46 chromosomes, while other cells have an abnormal 47 chromosomes.

Nondisjunction

A genetic term referring to an event which takes place during cell division, in which a genetic accident causes an egg or sperm cell to have 24 chromosomes, rather than the normal 23.

Translocation

A genetic term referring to a situation during cell division in which a piece of one chromosome breaks off and sticks to another chromosome.

Trisomy

The condition of having three identical chromosomes, instead of the normal two.

Further Reading

For Your Information

Books

• Carey, John C. "Chromosomal Disorders." In Rudolph's Pediatrics, edited by Abraham M. Rudolph. Stamford: Appleton & Lange, 1996.
• Shapiro, Larry J. "Human Genetics." In Nelson Textbook of Pediatrics, edited by Richard Behrman. Philadelphia: W.B. Saunders Co., 1996.
• Stray-Gunderson, K. Babies with Down Syndrome: A New Parents' Guide. Kensington: Woodbine House, 1986.
• Tingey, C. Down Syndrome: A Resource Handbook. Boston: Little, Brown, Inc., 1988.

  Periodicals

• Carlson, Tucker, and Jason Cowley. "When a Life is Worth Living: Down's Syndrome Children." The Times (November 29, 1996): 18+.
• "Medical and Surgical Care for Children with Down Syndrome." The Exceptional Parent 25 no. 11 (November 1995): 78+.
• Roan, Shari. "Elixir of Hope?" Los Angeles Times 115 (March 6, 1996): E1.

  Organizations

• National Down Syndrome Congress. 1605 Chantilly Drive, Suite 250, Atlanta, GA 30324-3269. (800) 232-6372.
• National Down Syndrome Society. 666 Broadway, 8th Floor, New York, NY 10012-2317. (800) 221-4602. http://www.ndss.org.

Gale Encyclopedia of Medicine. Gale Research, 1999.