Down Syndrome

views updated

Down Syndrome

Definition

Down syndrome is the most common chromosome disorder and genetic cause of mental retardation. It occurs because of the presence of an extra copy of chromosome 21. For this reason, it is also called trisomy 21.

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 the sperm cells from the father and egg cell from the mother are formed, they both undergo a reduction of their total number of chromosomes from 46 to 23. This process is called meiosis. When a baby is conceived by the combination of one sperm cell with one egg cell, the baby receives 23 chromosomes from each parent, for a total of 46 chromosomes. Occasionally, an error occurs in the reduction process. Instead of passing on 23 chromosomes to the baby, a parent will pass on 24 chromosomes. This event is called non-disjunction and occurs in 95% of Down syndrome cases. The baby, therefore, receives an extra chromosome at conception. In Down syndrome, this is an extra chromosome 21. The total number of chromosomes in individuals affected with Down syndrome is 47 instead of 46.

In approximately 1-2% of Down syndrome cases, the original egg and sperm cells cells contain the correct number of chromosomes, 23 each. 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 copy of chromosome 21. This form of genetic disorder is called mosaicism. An 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). Individuals affected with this mosaic form of Down syndrome generally have less severe signs and symptoms of the disorder.

Another relatively rare genetic accident that causes Down syndrome is called translocation. During cell division, chromosome 21 somehow breaks. The broken off piece of this 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.

Genetic profile

Down syndrome is usually the result of an extra copy of chromosome 21 (trisomy 21). As described earlier, Down syndrome may occur because of nondisjunction within the sperm, or more commonly, the egg cell; genetic mosaicism, which occurs after conception; or translocation, which also occurs after conception.

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. Women who are 34 and younger have a recurrence rate of 1% for having another Down syndrome child. Women who are 35 and older are at increased risk. The specific risk varies and increases as their age increases. When a 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 a balanced translocation. When one parent is a carrier of a balanced translocation, the chance of future offspring having Down syndrome is greatly increased. Specific risks must be assessed by a genetic counselor.

Demographics

The incidence of Down syndrome is about one in 800 live births. It affects an equal number of male and female babies. 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 significantly increases. 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. It is important to remember that not all children with Down syndrome will exhibit all of the features discussed. There is great variability in both the number and severity of characteristics. Babies with Down syndrome tend to be overly quiet, less responsive to stimuli, and have weak, floppy muscles. A number of physical signs may also be present. These include: a flat appearing face; brighter sparkles in the iris of the eye (Brushfield spots); a small head; a flat bridge of the nose; a smaller than normal, low-set nose; small mouth. This causes the tongue to stick out and to appear overly large. They have upward slanting eyes; extra folds of skin located at the inside corner of each eye, near the nose (epicanthal folds); rounded cheeks; and small, misshapen ears. They tend to have small, wide hands; an unusual deep crease across the center of the palm (simian crease); a curved little finger; a wide space between the great and the second toes; unusual creases on the soles of the feet; overly flexible joints (sometimes referred to as being double-jointed); and, a shorter than normal length.

Other types of problems often accompany Down syndrome. Approximately 30-50% of all children with Down syndrome are found to have 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. Another relatively common problem is a tracheo-esophageal fistula. This is an abnormal connection between the trachea (windpipe) and esophagus that interferes with both eating and breathing.

Other medical conditions occurring in persons with Down syndrome include an increased chance of developing infections, especially ear infections and pneumonia; certain kidney disorders; thyroid disease (especially low or hypothyroidism); hearing loss; vision impairment requiring glasses (corrective lenses); and a 20 times greater chance than the population as a whole of developing leukemia.

Development in a baby and child affected 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 unaffected peers. Talking is also quite delayed. The level of mental retardation is considered to be mild to moderate in people with Down syndrome. The degree of mental retardation varies greatly among children with Down syndrome. While it is impossible to predict the severity of Down syndrome at birth, with proper education, children who have Down syndrome are capable of learning. Most children with Down syndrome can read and write and are placed in special education classes at school. The majority of individuals with Down syndrome become semi-independent, meaning that they can take care of their own needs with some assistance. Many hold noncomplex 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). People without Down syndrome have a lifetime risk of 12% for developing Alzheimer's disease. In contrast, by age 40-50, almost all persons with Down syndrome will also develop Alzheimer's disease.

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 performed on other types of tissue, including the 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. A female with Down syndrome will have a 47, XX + 21 karyotype; a male with Down syndrome will have a 47 XY + 21 karyotype.

Women who are over the age of 35 are offered prenatal tests to determine if their developing baby is affected with Down syndrome. A genetic counselor meets with these families to inform them of the risks and to discuss the tests that are available to make a diagnosis prior to delivery. Because there is a slight risk of miscarriage following some prenatal tests, all testing is optional. Couples must decide whether or not they desire to take this risk to learn the status of their unborn baby. Couples must also decide if they wish to know whether or not the baby the mother carries has Down syndrome. Some couples choose not to have the test because they are certain they would not choose an abortion if they find theirs is a Down syndrome baby.

Ultrasound is now available for prenatal screening. Some abnormalities associated with Down syndrome, including intrauterine growth retardation, may be detected using ultrasound. The use of ultrasound as a screening test for Down syndrome is limited by the difficulty of producing reliable sonographic images of critical fetal structures.

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 are 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. All pregnant women under the age of 35 are offered a maternal serum alpha-fetoprotein (MSAFP) screen. This test is normally performed at 15-22 weeks of pregnancy. The MSAFP screen measures a protein and two hormones normally found in maternal blood during pregnancy. A specific pattern of these hormones and protein can give a pregnant woman an increased risk for having a baby born with Down syndrome. Carrying a baby with Down syndrome often causes MSAFP to be lower than normal. Test results reveal only an increased risk and cannot diagnose a baby born with Down syndrome. The MSAFP test can detect up to 60% of all babies who will be born with Down syndrome. Women with an increased risk are offered amniocentesis.

The only way to definitively (with about 99% accuracy) establish 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 chorionic villus sampling, usually performed at 10-12 weeks of pregnancy, 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 ). In amniocentesis, a small amount of the fluid in which the baby is floating is withdrawn with a long, thin needle. Both amniocentesis and CVS allow the baby's own karyotype to be determined. Both tests carry a small risk of causing miscarriage. The risk from CVS is 1% and the risk from amniocentesis is 0.5%. This small risk must be considered when deciding to perform these tests. If test information is positive for Down syndrome, a couple must then decide how to use this information to begin to prepare for the arrival of a baby with Down syndrome, to consider adoption for the baby or to terminate the pregnancy. It must be noted that while the results of prenatal tests can diagnose Down syndrome, they are unable to predict the severity of symptoms.

Treatment

No treatment is available to cure Down syndrome. Treatment is directed at addressing the individual concerns of a particular person. For example, heart defects will many times require surgical repair, as will duodenal atresia or a tracheo-esophageal fistula. Many persons with Down syndrome will need to wear glasses to correct vision. Persons 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 homes. This requires careful support and education of both parents and siblings. It is a life-changing event to learn that a new baby has a permanent condition that will affect essentially all aspects of 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).

As of 2001, the genetic sequence for chromosome 21 was fully determined, which may open the door to new approaches to the treatment of Down syndrome through the development of gene-specific therapies.

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 significantly vary. 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 to 55 years.

The prognosis for a baby born with Down syndrome continues to improve. Due to modern medical treatments, including antibiotics to treat infections and surgery to correct heart defects, duodenal atresia, and tracheo-esophageal fistula, 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.

Most men with Down syndrome appear to be sterile (meaning that they are unable to have offspring). There has been at least one report of a male with Down syndrome who fathered a child. Some women with Down syndrome, however, are capable of having babies. Approximately 40% of women with Down syndrome are unable to become pregnant. The risk of a woman with trisomy 21 to have a child with Down syndrome is approximately 50%.

Health care team roles

Obstetricians, nurse practitioners, or family doctors often make an initial recommendation that a woman be screened for Down syndrome. Depending on the test, a physician, phlebotomist, or ultrasonographer may obtain sample materials. A laboratory technician will process sample materials. A genetic counselor, physician or other person with specialized training usually provides test results to a couple or woman. Counselors must be available to assist a woman or couple to make appropriate decisions about their baby. Pediatricians, family doctors, internists, and geriatric physicians provide care throughout the life of an individual with Down syndrome. Other health professionals, including surgeons, eye specialists, and hearing experts, provide services as needed.

Prevention

As of 2001, there is no known way to prevent Down syndrome.

KEY TERMS

Cell— A fundamental unit of living tissue. The specialized nature of organs and tissues in a human body reflects the specialized structure and function of its constituent cells.

Chromosome— The structures that 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).

Genetic counseling— A communication process by which personal genetic risk information is translated into practical information for families. Genetic counselors are health care professionals with specialized training and experience in the areas of medical genetics and counseling.

Karyotype— The specific chromosomal makeup of a particular cell.

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

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

Nondisjunction— A genetic term referring to an event that 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.

Resources

BOOKS

Girod, Christina M. Down Syndrome. Farmington Hills, MI: Lucent Books, 2001.

Jones, Kenneth L. "Down syndrome." In Smith's Recognizable Patterns of Human Malformation, 5th ed. Edited by Richard E. Behrman et al., Philadelphia: Saunders, 1997, 8-14.

Miller, Jon F, Mark Leddy and Lewis A. Leavitt. Improving the Communication of People With Down Syndrome. Baltimore, MD: Paul H Brookes Publishers, 1999.

Pueschel, Sigfried M. A Parent's Guide to Down Syndrome: Toward a Brighter Future, 2nd ed. Baltimore, MD: Paul H. Brookes Publishers, 2000.

Van Allen, Margot and Judith C. Hill. "Congenital anomalies." In Cecil Textbook of Medicine, 21st ed. Edited by Lee Goldman and J. Claude Bennett. Philadelphia: W.B. Saunders, 2000, 150-153.

Weeks, Daniel J. Perceptual-Motor Behavior in Down Syndrome. Champaign, IL: Human Kinetics Publishing, 2000.

PERIODICALS

Kaiser, A. P., P. P. Hester, and A. S. McDuffie. "Supporting communication in young children with developmental disabilities." Mental Retardation and Developmental Disability Research Review 7, no. 2 (2001): 143-150.

Maymon, R., E. Dreazen, I. Buckovsky, Z. Weinraub, and A. Herman. "Does a 'notched' nuchal translucency indicate Down syndrome fetuses or other adverse pregnancy outcome?" Prenatal Diagnosis 21, no. 5 (2001): 403-408.

Palisano R. J., S. D. Walter, D. J. Russell, P. L. Rosenbaum, M. Gemus, B. E. Galuppi, and L. Cunningham. "Gross motor function of children with down syndrome: creation of motor growth curves." Archives of Physical Medicine and Rehabilitation 82, no. 4 (2001): 494-500.

Savulescu, J. "Resources, Down's syndrome, and cardiac surgery." British Medical Journal 322, no. 7291 (2001): 875-876.

Van Riper, M., and W. I. Cohen. "Caring for children with Down syndrome and their families." Journal of Pediatric Health Care 15, no. 3 (2001): 123-131.

Varela, A. M., L. B. Sardinha, and K. H. Pitetti. "Effects of an aerobic rowing training regimen in young adults with Down syndrome." American Journal of Mental Retardation 106, no. 2 (2001): 135-144.

ORGANIZATIONS

American Academy of Neurology, 1080 Montreal Avenue, St. Paul, Minnesota 55116. (651) 695-1940. Fax: (651) 695-2791. ?http://www.aan.com/?. [email protected].

American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, IL 60007-1098. (847) 434-4000. Fax: (847) 434-8000. ?http://www.aap.org/default.htm?. [email protected].

American Association on Mental Retardation, 444 North Capitol Street, NW, Suite 846, Washington, D.C. 20001-1512. (202) 387-1968 or (800) 424-3688. Fax: (202) 387-2193. ?http://www.aamr.org?.

American Speech-Language Hearing Association, 10801 Rockville Pike, Rockville, MD 20852. (800) 638-8255. ?http://www.asha.org/?. [email protected].

Association of Retarded Citizens of the United States, PO Box 6109, 2501 Avenue J, Arlington, TX 76011.

National Association for Down Syndrome, PO Box 4542, Oak Brook, IL 60522. (630) 325-9112. ?http://www.nads.org/?.

National Down Syndrome Congress, 7000 Peachtree-Dunwoody Road, NE, Lake Ridge 400 Office Park, Building #5, Suite 100, Atlanta, GA 30328-1655. (800) 232-6372 or (770) 604-9500. ?http://www.ndsccenter.org/?. [email protected].

National Down Syndrome Society, 666 Broadway, New York, NY 10012. (212) 460-9330 or (800) 221-4602. Fax: (212) 979-2873. ?http://www.ndss.org/?.