Down Syndrome

Clinical Features

Down syndrome is associated with a characteristic physical appearance, mental retardation, and specific birth defects or health conditions. The facial features, in addition to low muscle tone (called hypotonia), are often the first signs that alert a physician to a potential diagnosis of Down syndrome. These features include an up-slant of the outer corners of the eyes, small skin folds over the inner corners of the eyes, a small nose with a flat nasal bridge, a flat profile, and a large, grooved tongue that often protrudes from the mouth. Other physical characteristics can include a short neck, excess skin on the back of the neck, short hands with a single palmar crease, a wide gap between the first and second toes, and short stature. There are many individuals without Down syndrome who may have one or more of these features. It is only when the features occur together and the appropriate genetic test (chromosome studies) confirms clinical suspicion that a diagnosis of Down syndrome is made.

All individuals with Down syndrome have mental retardation, usually mild to moderate. The degree of learning disability may not be immediately apparent, since social ability generally exceeds scholastic ability. Early intervention programs are important for giving people with Down syndrome the best chance to maximize their learning potential.

Certain birth defects and health conditions are more common in individuals with Down syndrome. The most common birth defect is a congenital heart defect, affecting 40 percent to 50 percent of newborns with the condition. Although many can be repaired with surgery, congenital heart defects remain the major cause of early death among affected persons. Individuals with Down syndrome have an increased chance of experiencing hearing loss, vision problems, and thyroid disease, as well as an increased susceptibility to infections. Because of such concerns, specific guidelines for the health care of individuals with Down syndrome have been developed.

Chromosomal Basis of Down Syndrome

In 1959 French geneticist Jerome Lejeune recognized that individuals with Down syndrome have forty-seven chromosomes instead of the usual forty-six. Later, it was determined that it is an extra copy of chromosome 21 that causes the condition. It is not yet clear how the extra chromosome causes the clinical features, although it is believed that an "extra dose" of one or more of the genes on the chromosome is responsible.

There are three types of Down syndrome: trisomy 21, mosaic Down syndrome, and translocation Down syndrome. In 94 percent of cases, the extra copy of chromosome 21 stands alone (is not attached to any other chromosomes) and is present in every cell of the body. This is called trisomy 21, trisomy meaning three.

Trisomy 21 occurs due to a chromosome packaging error. Usually when the body makes its sex cells (egg or sperm cells) during meiosis, it packages up one chromosome from each pair. However, sometimes an error (nondisjunction) occurs, causing both chromosomes from a pair to get packaged together. If the sex cell with the extra chromosome is fertilized by a sex cell with the usual chromosome number, the resulting embryo will have a trisomy. If the extra chromosome is chromosome 21, the embryo will have Down syndrome. About 75 percent of embryos with trisomy 21 abort spontaneously before birth. Nondisjunction occurs by chance in the making of both egg and sperm cells, but it happens more often in egg cells as women get older. Thus, the chance of having a baby with Down syndrome increases with increasing maternal age.

Translocation Down syndrome, which accounts for 3 percent to 4 percent of cases, occurs when the extra copy of chromosome 21 is attached to another chromosome. In about one-fourth of the cases where a person has translocation Down syndrome, he or she inherited the translocation from a parent. Therefore it is important to test the parents' chromosomes in these cases, for purposes of future family planning.

The third type of Down syndrome is the mosaic type, which occurs in 2 percent to 3 percent of cases. In mosaic Down syndrome, a person has some cells with an extra copy of chromosome 21 and some cells with the usual two copies. People with mosaic Down syndrome may or may not have milder symptoms than people with "full" trisomy 21.

Testing for Down Syndrome

Cytogenetic analysis looks at the number and structure of a person's chromosomes. This test, which can be performed on a blood sample, is the test used to definitively determine if an individual has Down syndrome.

Prenatal diagnosis for Down syndrome (testing for the condition during pregnancy) is possible. Chromosome studies can be performed on fetal cells collected via chorionic villus sampling (CVS) at ten to twelve weeks of pregnancy or by amniocentesis at fifteen to twenty weeks of pregnancy. Because of the link between the mother's age and the chance of Down syndrome, prenatal diagnosis for Down syndrome and other chromosome conditions is routinely offered to women thirty-five and older. Whether to pursue prenatal diagnosis is a personal decision that can only be made by the parents.

SEE ALSO BIRTH DEFECTS; CHROMOSOMAL ABERRATIONS; MEIOSIS; MOSAICISM; NONDISJUNCTION; PRENATAL DIAGNOSIS.

Angela Trepanier

and Gerald L. Feldman

Bibliography

Evans, Mark I., et al. Fetal Diagnosis and Therapy: Science, Ethics, and the Law. Philadelphia, PA: JB Lippincott Co., 1989.

Gardner, R., J. McKinlay, and Grant R. Sutherland. Chromosome Abnormalities and Genetic Counseling, 2nd ed. New York: Oxford University Press, 1996.

Nussbaum, Robert L., Roderick R. McInnes, and Huntington F. Willard, eds. Thompson & Thompson Genetics in Medicine, 6th ed. Philadelphia, PA: W. B. Saunders, 2001.

Pueschel, Siegfried M., ed. A Parent's Guide to Down Syndrome: Toward a Brighter Future, 2nd ed. Baltimore, MD: Paul H. Brooks Publishing, 2001.

Internet Resource

Cohen, William I., ed. "Health Care Guidelines for Individuals with Down Syndrome: 1999 Revision." Down Syndrome Quarterly 4, no. 3 (1999): 1-15. <http://www.denison.edu/dsq/health99.shtml>.