Down Syndrome

Definition

Down syndrome (DS) is the most common cause of mental retardation and malformation in a newborn. It occurs because of the presence of an extra chromosome. It was first described in 1866 by Dr. John L. H. Down (1828–1896), an English physician.

Down syndrome occurs about once in every 800 births. It is estimated that about 6,000 children are born with DS each year in the United States.

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 one in every 800-1,000 births. It affects an equal number of boys and girls. 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.

Down syndrome sometimes occurs together with such other developmental disorders as Rett syndrome. Although such double diagnoses are very rare, it is important for parents to recognize that the presence of one chromosomal abnormality does not exclude the possibility that their child may have a second anomaly.

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 that 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 that 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 that 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 (a blood disorder).

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 six in 100 risk of developing Alzheimer's, but people with Down syndrome have a 25 in 100 chance of the disease. In addition to an increased risk of developing Alzheimer's, patients with DS show the first signs of the disease much earlier than most people, often in their early 40s. Alzheimer's disease causes the brain to shrink and to break down. The number of brain cells decreases, and abnormal deposits and structural rearrangements 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. A new questionnaire was published in 2004 to help doctors evaluate adults with Down syndrome for symptoms of Alzheimer's-related dementia.

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.

A drug known as piracetam received some attention in the treatment of Down syndrome patients in the mid-1990s. Piracetam is a so-called "smart drug" that is marketed in Europe and Japan to normal adults hoping to increase their cognitive abilities. It is also sold to skiers and mountain climbers as a remedy for loss of concentration at high altitudes. Although some European researchers have studied piracetam as a possible treatment for dementia in Alzheimer's disease, none of these trials have shown as of 2004 that the drug is of any benefit to Alzheimer's patients. Piracetam is not approved for use in the United States; several large shipments of it were seized by the Food and Drug Administration in 2004. Piracetam can be obtained via the Internet but is not recommended by mainstream medical practitioners.

In 1998 the European company licensed to produce piracetam, UCB Pharma in Belgium, issued a statement discouraging its use in children with Down syndrome. The company obtained orphan drug status for piracetam from the FDA in the early 2000s and has conducted a controlled trial of the drug as a possible treatment for muscle spasms (myoclonus) in children.

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 approach, however, 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 that 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 educational practice 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. The most common cause of death is heart disease.

Still, the prognosis for a baby born with Down syndrome in the early 2000s 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 that 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 conveys the genetic defect to the next generation 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 requires evaluation by a genetic counselor.

KEY TERMS

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).

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.

Orphan drug— A term for a drug that treats a rare disease, defined by the Food and Drug Administration (FDA) as one that affects fewer than 200,000 Americans. The FDA has an Office of Orphan Products Development (OOPD), which offers grants to researchers to develop these products.

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

Beers, Mark H., MD, and Robert Berkow, MD, editors. "Congenital Anomalies." Section 19, Chapter 261 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.

Tierney, Lawrence, et al. Current Medical Diagnosis and Treatment. Los Altos, CA: Lange Medical Publications, 2001.

PERIODICALS

Chen, Harold, MD. "Down Syndrome." eMedicine December 6, 2004. 〈http://www.emedicine.com/med/topic567.htm〉.

Egan, J. F., P. A. Benn, C. M. Zelop, et al. "Down Syndrome Births in the United States from 1989 to 2001." American Journal of Obstetrics and Gynecology 191 (September 2004): 1044-1048.

Evans, J. G., G. Wilcock, and J. Birks. "Evidence-Based Pharmacotherapy of Alzheimer's Disease." International Journal of Neuropsychopharmacology 7 (September 2004): 351-369.

Leonard, H., L. Weaving, P. Eastaugh, et al. "Trisomy 21 and Rett Syndrome: A Double Burden." Journal of Paediatrics and Child Health 40 (July 2004): 406-409.

Prasher, V., A. Farooq, and R. Holder. "The Adaptive Behaviour Dementia Questionnaire (ABDQ): Screening Questionnaire for Dementia in Alzheimer's Disease in Adults with Down Syndrome." Research in Developmental Disabilities 25 (July-August 2004): 385-397.

Tanner, Lindsey. "Study: Drug May Hurt Syndrome Kids." Chicago: Associated Press April 12, 2001.

Tyler, C., and J. C. Edman. "Down Syndrome, Turner Syndrome, and Klinefelter Syndrome: Primary Care throughout the Life Span." Primary Care 31 (September 2004): 627-648.

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〉.

National Organization for Rare Disorders (NORD). 55 Kenosia Avenue, P. O. Box 1968, Danbury, CT 06813-1968. (203) 744-0100. Fax: (203) 798-2291. 〈http://www.rarediseases.org〉.

United States Food and Drug Administration (FDA). 5600 Fishers Lane, Rockville, MD 20857-0001. (888) INFO-FDA. 〈http://www.fda.gov〉.

OTHER

Food and Drug Administration (FDA). "Grants Awarded by the OOPD Program." 〈http://www.fda.gov/orphan/grants/previous.htm〉.

Food and Drug Administration (FDA). "Refusal Actions by FDA as Recorded in OASIS for China (Mainland). August 2004." 〈http://www.fda.gov/ora/oasis/1/ora_oasis_c_cn.html〉.

Leshin, Lem, MD. "Piracetam and Down Syndrome." http://www.ds-health.com/piracet.html.

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 to 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 1 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 to 50% of all children with Down syndrome are found to have heart defects.

Malformations of the gastrointestinal tract are present in about 5 to 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 non-complex 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 tracheoesophageal fistula, life expectancy has greatly increased. Community and family support allows people with

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.

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.

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. 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. Goldman, Lee and Bennett, J. Claude. 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 out-come?" 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/>. info@aan.org.

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>. kidsdoc@aap.org.

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/>. actioncenter@asha.org.

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/>. ndsccenter@aol.com.

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/>.

OTHER

Administration on Developmental Disabilities (Dept of Health and Human Services). <http://www.acf.dhhs.gov/programs/add/index.htm>.

Arc. <http://www.thearc.org/faqs/down.html>.

Children With Disabilities. <http://www.childrenwithdisabilities.ncjrs.org/>.

Disability Solutions. <http://www.disabilitysolutions.org/>.

National Council on Disability. <http://www.ncd.gov/>.

Resources for Children with Special Needs. <http://www.childrenwithdisabilities.ncjrs.org/>.

L. Fleming Fallon, Jr., MD, DrPH

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/〉. info@aan.org.

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〉. kidsdoc@aap.org.

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/〉. actioncenter@asha.org.

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/〉. ndsccenter@aol.com.

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/〉.

OTHER

Administration on Developmental Disabilities (Dept of Health and Human Services). 〈http://www.acf.dhhs.gov/programs/add/index.htm〉.

Arc. 〈http://www.thearc.org/faqs/down.html〉.

Children With Disabilities. 〈http://www.childrenwithdisabilities.ncjrs.org/〉.

Disability Solutions. 〈http://www.disabilitysolutions.org/〉.

National Council on Disability. 〈http://www.ncd.gov/〉.

Resources for Children with Special Needs. 〈http://www.childrenwithdisabilities.ncjrs.org/〉.

Down syndrome

Definition

Down syndrome is the most common cause of mental retardation and malformation in a newborn. A genetic disorder, it occurs because of the presence of an extra chromosome.

Description

Chromosomes are 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 combining 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 when 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 number 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 percent of cases of Down syndrome.

Demographics

Down syndrome occurs in about one in every 800 to 1,000 births. It affects an equal number of boys and girls. Less than 25 percent 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 to 50 percent 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 that 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 that 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 percent 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 that 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 that requires corrective lenses; and a 20-times greater chance of developing leukemia (a blood disorder).

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 dementia or senility). Most people have a six in 100 risk of developing Alzheimer's, but people with Down syndrome have a one-in-four 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 loss of brain function. People with Alzheimer's have strikingly faulty memories. Over time, people with Alzheimer's disease 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 medical difficulties, 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

As of 2004 no treatment is available to cure Down syndrome. Treatment is directed at addressing the individual concerns of a particular patient. For example, heart defects often times require surgical repair, as will duodenal atresia. Many Down syndrome patients need to wear glasses to correct vision. Patients with hearing impairment benefit from hearing aids.

In the mid 1900s, all Down syndrome children were quickly placed into institutions for lifelong care. Research shows, however, that the best outlook for children with Down syndrome is family life in their own home. This arrangement requires careful support and education of the parents and the siblings. Parents and other siblings face a life-changing event in receiving a new baby who has a permanent condition that will affect essentially all aspects of his or her development. Some community groups are committed to helping families deal with the emotional effects of this new situation. Schools are required to provide services for children with Down syndrome, sometimes in separate special education classrooms and sometimes in regular classrooms, a practiced 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 percent 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 at death for an individual with Down syndrome is about 50 to 55 years.

Still, in the early 2000s, 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 and in some cases 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 percent 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 percent of the time. Other screening tests measure and compare the levels of other markers present in the mother's blood. A specialized ultrasound exam measures the thickness of the back of the fetus's neck (called nuchal lucency). Thicker measurements correlate with the possibility of Down syndrome or other chromosomal abnormalities.

KEY TERMS

Chromosome —A microscopic thread-like structure found within each cell of the human body and consisting of a complex of proteins and DNA. Humans have 46 chromosomes arranged into 23 pairs. Chromosomes contain the genetic information necessary to direct the development and functioning of all cells and systems in the body. They pass on hereditary traits from parents to child (like eye color) and determine whether the child will be male or female.

Karyotype —A standard arrangement of photographic or computer-generated images of chromosome pairs from a cell in ascending numerical order, from largest to smallest.

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 —An event that takes place during cell division in which a chromosome pair does not separate as it should. The result is an abnormal number of chromosmes in the daughter cells produced by that cell division.

Translocation —The transfer of one part of a chromosome to another chromosome during cell division. A balanced translocation occurs when pieces from two different chromosomes exchange places without loss or gain of any chromosome material. An unbalanced translocation involves the unequal loss or gain of genetic information between two chromosomes.

Trisomy —An abnormal condition where three copies of one chromosome are present in the cells of an individual's body instead of two, the normal number.

All of these screening tests are used to decide which mothers will be offered other, more definitive testing to ascertain whether the baby has Down syndrome. These more definitive tests each carry a risk of miscarriage, which is why screening tests are an important first step. 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 that 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 other 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.

Parental concerns

Parenting a child with Down syndrome can be both challenging and rewarding. Children with Down syndrome have a wide range of potential outcomes. Early intervention programs have been proven to be of great help in assisting these children in achieving the highest level of functioning possible. There are many support groups available for parents and siblings of Down syndrome children.

Resources

BOOKS

Hall, Judith G. "Chromosomal Clinical Abnormalities." In Nelson Textbook of Pediatrics. Edited by Richard E. Behrman et al. Philadelphia: Saunders, 2004.

Simpson, Joe Leigh. "Genetic Counseling and Prenatal Diagnosis." In Obstetrics: Normal and Problem Pregnancies. Edited by Steven G. Gabbe. London: Churchill Livingstone, 2002.

Tierney, Lawrence, et al. Current Medical Diagnosis and Treatment. Los Altos, CA: Lange Medical Publications, 2001.Periodicals

Canick, J. A. "Prenatal screening for Down syndrome: current and future methods." Clinical Laboratory Medicine 86 (June 2003): 395–411.

Roizen, N. J. "Medical care and monitoring for the adolescent with Down syndrome." Adolescent Medicine 13 (June 2002): 345–58.

Tyler, C. "Down syndrome, Turner syndrome, and Klinefelter syndrome: primary care throughout the life span." Primary Care 31 (September 2004): 627.

ORGANIZATION

National Down Syndrome Congress. 1370 Center Drive, Suite 102 Atlanta, GA 30338 (800) 232-6372. Web site: <www.ndsccenter.org>

National Down Syndrome Society. 666 Broadway, 8th Floor, New York, NY 10012-2317. Web site: <www.ndss.org>.

Kim A. Sharp, M.Ln. Rosalyn Carson-DeWitt, MD

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

When a baby is conceived, the sperm cell from the father and the egg cell from the mother undergo a reduction of the total number of chromosomes from 46 to 23. Occasionally an error occurs in this reduction process and instead of passing on 23 chromosomes to the baby, a parent will pass on 24 chromosomes. This event is called nondisjunction and it occurs in 95% of Down syndrome cases. The baby therefore receives an extra chromosome at conception. In Down syndrome, that extra chromosome is chromosome 21. Because of this extra chromosome 21, individuals affected with Down syndrome have 47 instead of 46 chromosomes.

Genetic profile

In approximately one to two percent of Down syndrome cases, the original egg and sperm cells contain the correct number of chromosomes, 23 each. The problem occurs sometime shortly after fertilization—during the phase when 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. 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). 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.

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. Mothers under the age of 35 with one Down syndrome-affected child have a 1% chance that a second child will also be born with Down syndrome. In mothers 35 and older, the chance of a second child being affected with Down syndrome is approximately 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 a balanced translocation. A carrier has rearranged chromosomal information and can pass it on, but he or she does not have an extra chromosome and therefore is not affected with 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 assessed by a genetic counselor.

Demographics

Down syndrome occurs in about one in every 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 increases significantly. 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.

Down syndrome occurs with equal frequency across all ethnic groups and subpopulations.

Signs 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. Not all affected babies will exhibit all of the symptoms discussed. There is a large variability in the number and severity of these characteristics from one affected individual to the next. 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; a small head; a flat bridge of the nose; a smaller than normal, low-set nose; small mouth, which causes the tongue to stick out and to appear overly large; upward slanting eyes; bright speckles on the iris of the eye (Brushfield spots); extra folds of skin located at the inside corner of each eye near the nose (epicanthal folds); rounded cheeks; small, misshapen ears; small, wide hands; an unusual deep crease across the center of the palm (simian crease); an inwardly 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 shorter-than-normal stature.

Other types of defects often accompany Down syndrome. Approximately 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. All of these result in abnormal patterns of blood flow within the heart. Abnormal blood flow within the heart often means that less oxygen is sent into circulation throughout the body, which can cause fatigue, a lack of energy, and poor muscle tone.

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 malformation of the gastrointestinal tract that is seen in patients with Down syndrome is an abnormal connection between the windpipe (trachea) and the digestive tube of the throat (esophagus) called a tracheoesophageal fistula (T-E fistula). This connection interferes with eating and/or breathing because it allows air to enter the digestive system and/or food to enter the airway.

Other medical conditions occurring 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 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 Down syndrome. The degree of mental retardation varies a great deal from one child to the next. 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 affected with Down syndrome can read and write and are placed in special education classes in school. The majority of individuals with Down syndrome become semi-independent adults, meaning that they can take care of their own needs with some assistance.

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 12% chance of developing Alzheimer's, but almost all people with Down syndrome will have either Alzheimer disease or a similar type of dementia by the age of 50. Alzheimer 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.

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 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 . An individual with Down syndrome will have a 47 XX+21 karyotype if they are female and a 47 XY+21 karyotype if they are male.

Women who become pregnant after the age of 35 are offered prenatal tests to determine whether or not 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 types of tests available to make a diagnosis prior to delivery. Because there is a slight risk of miscarriage following some prenatal tests, all testing is optional, and couples need to decide whether or not they desire to take this risk in order to learn the status of their unborn baby.

Screening tests are used to estimate the chance that an individual woman will have a baby with Down syndrome. A test called the maternal serum alpha-fetoprotein test (MSAFP) is offered to all pregnant women under the age of 35. If the mother decides to have this test, it is performed between 15 and 22 weeks of pregnancy. The MSAFP screen measures a protein and two hormones that are normally found in maternal blood during pregnancy. A specific pattern of these hormones and protein can indicate an increased risk for having a baby born with Down syndrome. However, this is only a risk and MSAFP cannot diagnose Down syndrome directly. Women found to have an increased risk of their babies being affected with Down syndrome are offered amniocentesis . The MSAFP test can detect up to 60% of all babies who will be born with Down syndrome.

Ultrasound screening for Down syndrome is also available. This is generally performed in the mid-trimester of pregnancy. Abnormal growth patterns characteristic of Down syndrome such as growth retardation, heart defects, duodenal atresia, T-E fistula, shorter than normal long-bone lengths, and extra folds of skin along the back of the neck of the developing fetus may all be observed via ultrasonic imaging.

The only way to definitively establish (with about 99% accuracy) the presence or absence of Down syndrome in a developing baby is to test tissue during the pregnancy itself. This is usually done either by amniocentesis, or chorionic villus sampling (CVS). All women under the age of 35 who show a high risk for having a

baby affected with Down syndrome via an MSAFP screen and all mothers over the age of 35 are offered either CVS or amniocentesis. In CVS, a tiny tube is inserted into the opening of the uterus to retrieve a small sample of the placenta (the organ that 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. CVS may be performed as early as 10 to 12 weeks into a pregnancy. Amniocentesis is generally not performed until at least the fifteenth week. Both CVS and amniocentesis carry small risks of miscarriage. Approximately 1% of women miscarry after undergoing CVS testing, while approximately one-half of one percent miscarry after undergoing amniocentesis. Both amniocentesis and CVS allow the baby's own karyotype to be determined.

Approximately 75% of all babies diagnosed prenatally as affected with Down syndrome do not survive to term and spontaneously miscarry. In addition, these prenatal tests can only diagnose Down syndrome, not the severity of the symptoms that the unborn child will experience. For this reason, a couple might use this information to begin to prepare for the arrival of a baby with Down syndrome, to terminate the pregnancy, or in the case of miscarriage or termination, decide whether to consider adoption as an alternative.

Treatment and management

No treatment is available to cure Down syndrome. Treatment is directed at addressing the individual concerns of a particular patient. For example, heart defects may require surgical repair, as will duodenal atresia and T-E fistula. 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 children with Down syndrome were quickly placed into institutions for lifelong care, research shows very clearly that the best out-look 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 that will affect essentially all aspects of his or her development. Some community groups help families deal with the emotional effects of raising a child with Down syndrome. Schools are required to provide services to children with Down syndrome, sometimes in separate special education classrooms, and sometimes in regular classrooms (this is called mainstreaming or inclusion).

In May 2000, the genetic sequence for chromosome 21 was fully determined, which opens the door to new approaches to the treatment of Down syndrome through the development of gene-specific therapies.

Prognosis

The prognosis for an individual with Down syndrome is quite variable, depending on the types of complications (heart defects, susceptibility to infections, development of leukemia, etc.). 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 to 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.

There has only been one report of a male affected with Down syndrome becoming a father. Approximately 60% of women with Down syndrome are fully capable of having children. The risk of a woman with trisomy 21 having a child affected with Down syndrome is 50%.

Resources

BOOKS

Pueschel, Siegfried M. A Parent's Guide to Down Syndrome: Toward a Brighter Future. Revised ed. New York: Paul H. Brookes Publishing Co., 2000.

Selikowitz, Mark. Down Syndrome: The Facts. 2nd ed. London: Oxford University Press, 1997.

Stray-Gunderson, K. Babies with Down Syndrome: A New Parents' Guide. Kensington: Woodbine House, 1986.

PERIODICALS

Carlson, Tucker, and Jason Cowley. "When a Life is Worth Living: Down's Syndrome Children." The Times (29 November 1996): 18+.

Cohen, William, ed. "Health Care Guidelines for Individuals with Down Syndrome: 1999 Revision." Down Syndrome Quarterly (September 1999).

Hattori, M., A. Fujiyama, D. Taylor, H. Watanabe, et al. "The DNA sequence of human chromosome 21." Nature (18 May 2000): 311–19.

ORGANIZATIONS

National Down Syndrome Congress. 7000 Peachtree-Dunwoody Rd., Bldg 5, Suite 100, Atlanta, GA 30328-1662. (770) 604-9500 or (800) 232-6372. Fax: (770) 604-9898. ndsccenter@aol.com. <http://www.ndsccenter.org>.

National Down Syndrome Society. 666 Broadway, New York, NY 10012-2317. (212) 460-9330 or (800) 221-4602. Fax: (212) 979-2873. <http://www.ndss.orginfo@ndss.org>.

WEBSITES

Down Syndrome Health Issues. <http://www.ds-health.com/>. (15 February 2001).

Down Syndrome Information Network. <http://www.downsyndrome.net/>. (15 February 2001).

Down Syndrome WWW Page. <http://www.nas.com/downsyn/>. (15 February 2001).

Recommended Down Syndrome Sites on the Internet. <http://www.ds-health.com/ds_sites.htm#natl>. (15 February 2001).

Paul A. Johnson