Down Syndrome

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Down Syndrome

Down syndrome is the most common cause of mental retardation. It is caused by the presence of an extra chromosome. Chromosomes contain sequences of deoxyribonucleic acid (DNA) called genes, which represent the genetic information that exists within a cell. Twenty-three distinctive pairs of chromosomes (46 in total), are located within the nucleus (a region of the cell that is bounded by a sepcialized membrane, and which houses the genetic material). When a sperm cell fertilizes an egg cell, the newly created zygote normally receives 23 chromosomes from each parent. The contribution of genetic information from each parent is what makes each baby a distinctive blend of both parental characteristics. But, in Down syndrome, a mistake during division of the sperm or egg cell produces a cell with an extra chromosome 21. This event occurs during cell division and is referred to as nondisjunction, or the failure of all chromosomes to separately properly resulting in retention of one of the chromosomes in one of the two new daughter cells. This event is also called trisomy 21 and accounts for approximately 95% of all Down syndrome patients.

In a very rare number of Down syndrome cases, the original egg and sperm cells begins with the correct number of chromosomes but shortly after fertilization during the phase where cells are dividing rapidly, a single cell can divide abnormally, creating a line of cells with an extra chromosome 21. This is called a cell line mosaicism. The individual with this type of Down syndrome has two types of cells: some with 46 chromosomes (the normal number), and some with 47 chromosomes (causing Down syndrome symptomatology). Individuals who are mosaic for trisomy 21 typically have less severe signs and symptoms of the disorder.

Another relatively rare genetic abnormality that can cause Down syndrome is called a chromosome translocation. This is an event that unlike the numerical abnormality causing trisomy 21, there is a structural

abnormality. Exchange of material from two different chromosomes during the production of sex cells can take place such that there is a whole chromosome 21 attached to another chromosome but the chromosome number is normal. These types of translocations, involving chromosome 21, occur in about 3–4% of cases of Down syndrome.

Down syndrome occurs in about one in every 800 liveborns. It affects an equal number of male and female babies. The majority of cases of Down syndrome occur due to a nondisjunction event that occurs in the maternal sex cells. As the maternal age increases, the risk of having a Down syndrome baby increases significantly. For example, at younger ages, the risk is about one in 1, 250. By the time the woman is 35 years old, the risk increases to one in 385; by age 40 the risk increases to one in 100; and by age 45 the risk is one in 25. There is no known maternal age-related increased risk if down syndrome results from either a cell line mosaicism or translocation.

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 a flat appearing face; smaller than normal head; flat bridge of the nose; smaller than normal, low-set nose; small mouth, with a protruding tongue; upward slanting eyes; extra folds of skin located at the inside corner of each eye, near the nose (epicanthal folds); small, outwardly rotated ears; small, wide

KEY TERMS

Chromosomes— The structures that carry genetic information in the form of DNA. 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 of chromosomes in humans is 46 (23 pairs).

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

Egg cell— The female’s reproductive sex cell.

Embryo— A stage in development after fertilization.

Karyotype— The specific chromosomal makeup of a particular cell.

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

Nondisjunction— A genetic term referring to an event that takes place during cell division in which one of the newly created cells has 24 chromosomes and the other cell has 22, rather than the normal 23.

Sperm— Substance secreted by the testes during sexual intercourse. Sperm includes spermatozoon, the mature male cell which is propelled by a tail and has the ability to fertilize the female egg.

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.

Zygote— The cell resulting from the fusion of male sperm and the female egg. Normally the zygote has double the chromosome number of either gamete, and gives rise to a new embryo.

hands; an unusual, deep crease across the center of the palm (simian crease); malformed fifth finger; wide space between the big and the second toes; unusual creases on the soles of the feet; and, later in childhood, shorter than normal height.

Other types of defects often accompany Down syndrome. About one third of all children with Down syndrome have heart defects. These heart defects are characteristic of Down syndrome, including abnormal openings (or holes) in the walls which separate the heart’s chambers (atrial septal defect, ventricular septal defect). These defects result in abnormal patterns of blood flow within the heart, resulting in inefficient oxygen delivery.

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 surgically repaired.

Developmental milestones in a child with Down syndrome are delayed. Due to weak, floppy muscles (hypotonia), babies learn to sit up, crawl, and walk much later than their normal peers. Talking is also delayed. The extent of delayed brain development is considered to be mild-to-moderate. Most people with Down syndrome can learn to perform regular tasks and can have relatively easy jobs (with supervision).

As people with Down syndrome age, they face an increased risk of developing Alzheimer disease, a degenerative disease that affects the brain. This occurs several decades earlier than the risk of developing Alzheimer disease in the general population. As people with Down syndrome age, they also have an increased chance of developing a number of other illnesses, including cataracts, thyroid problems, diabetes, leukemia, and seizure disorders.

There is no cure for Down syndrome. However, some of the clinical manifestations can be treated. For example, heart defects and duodenal atresia can often be corrected with surgical repair. In general, Down syndrome people tend to be easy going and good natured. The prognosis in Down syndrome is variable, depending on the types of complications (heart defects, susceptibility to infections, leukemia) of each affected individual. The severity of the developmental delay also varies. Without the presence of heart defects, about 90% of children with Down syndrome survive past their teenage years. In fact, people with Down syndrome can live until they are 50 years old.

Diagnosis and prevention

Down syndrome can be diagnosed at birth, when the characteristic physical signs of Down syndrome are noted and chromosome analysis can also be performed to confirm the diagnosis and determine the recurrence risks.

At-risk pregnancies are referred for genetic counseling and prenatal diagnosis. Screening tests are available during a pregnancy to determine if the fetus has Down syndrome. During 14–17 weeks of pregnancy, a substance called AFP (alpha-fetoprotein) can be measured. AFP is normally found circulating in a pregnant woman’s blood, 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.

A common method to directly determine whether the fetus has Down syndrome, is to test tissue from the fetus. 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 chorionic villus (tissue that surrounds the growing fetus). Chromosome analysis follow both amniocentesis and CVS to determine whether the fetus is affected.