Down Syndrome is a genetic condition caused by extra genetic material from the 21st chromosome.

Down Syndrome

Down Syndrome is a genetic condition caused by extra genetic material from the 21st chromosome. The extra genes cause certain characteristics that we know as Down syndrome. Individuals with Down syndrome also have all the other genes given to them by their parents. As a result, they have a combination of features typical of Down syndrome on top of the individual features from their parents. There is some degree of mental retardation, or cognitive disability and other developmental delays.

Individuals with Down syndrome have distinct physical characteristics; generally they are more similar to the average person in the community than they are different. The physical features are important to the physician in making the clinical diagnosis, but no emphasis should be put on those characteristics otherwise. Not every child with Down syndrome has all the characteristics; some may only have a few, an others may show most of the signs of Down syndrome.

Over a 120 features have been described in Down syndrome. Many children with the syndrome have no more than six or seven of these. Some of the features are those that are either particularly useful in recognizing the condition, or have some relevance to parents.

ØFace. When looked at from the front, the child with Down syndrome usually has a rounded face. From the side, the face tends to have a flat profile.

ØHead. The back of the head is slightly flattened in most people with Down syndrome. This is known as brachycephaly.

ØEyes. The eyes of nearly all children and adults with Down syndrome slant slightly upwards. In addition, there is often a small fold of skin that funs vertically between the inner comer of the eye and the bridge of the nose. This is known as the epicanthic fold or epicanthus. It is often seen in normal infants. In both normal children and those with Down syndrome it becomes less prominent, and may disappear, when the child grows older and the skin is taken up to cover the bridge of the nose. It is important only because prominent epicanthic folds may give a false impression of crossed eyes in children.

The eyes may have white or light-yellow speckling around the rum of the iris. These specks are called Brushfield spots, and may be present in the eyes of normal children. They often disappear later if the iris turns brown. Like epicanthic folds, they do not interfere with vision.

ØMouth. The mouth cavity is slightly smaller than average, and the tongue slightly larger. This combination encourages some children to acquire the habit of putting out their tongues at times.

ØHands. The hands tend to be broad, with short fingers. The little finger sometimes has only one joint instead of the usual two. This finger may also be slightly curbed towards the other fingers. The palm may have only one cease going across it or, if there are two, both may extend right across the hand.

ØBody size. Children with Down syndrome usually weigh less than average at birth. Their length at birth is similarly reduces. During childhood, they grow steadily but slowly, and their ultimate height as adults is generally shorter than would be expected for their family. It is usually near the bottom of the normal range, and is approximately 145 to 168 cm in men and 132 to 155 cm in women.

One of the more notable aspects of Down syndrome is the wide variety of features and characteristics of people with trisomy 21: There is a wide range of mental retardation and developmental delay noted among children with Down syndrome. Some babies are born with heart defects and others are not. Some children have associated illnesses such as epilepsy, hypothyroidism or celiac disease, and others don not. The first possible reason is the difference in the genes that are triplicated. Genes can come in different alternate forms, called “alleles”. The effect of over expression of genes may depend on which allele is present in the person with trisomy 21. The second reason that might be involved is called “penetrance”. If one allele causes a condition to be present in some people but not others, that is called “variable penetrance,” and that appears to be what happens with trisomy 21: the alleles don not do the same thing to every person who has it. Both reasons may be why there is such variation in children and adults with Down syndrome.

RELATIONSHIP OF DOWN SYNDROME INCIDENCE TO MOTHERS’ AGE

Mothers AgeIncidence of Down SyndromeSource: Hook, E.G., Lindsjo, A. Down Syndrome in Live Births by Single Year Maternal Age.

Although many theories have been developed, it is not known what actually causes Down syndrome. Some professionals believe that hormonal abnormalities, X-rays, viral infections, immunologic problems, or genetic predisposition may be the cause of the improper cell division resulting in Down syndrome. It has been know for some time that the risk of having a child with Down syndrome increases with advancing age of the mother. As the older the mother gets when she has children, the greater the possibility that she may have a child with Down syndrome. However, most babies with Down syndrome (more that 85 per cent) are born to mothers younger than 35 years. Some investigators reported that older fathers might also be at an increased risk of having a child with Down syndrome. It is well known that the extra chromosome in trisomy 21 could either originate in the mother of the father. Most often, however, the extra chromosome is coming from the mother. Parents who have a child with Down syndrome have an increased risk of having another child with Down syndrome in future pregnancies. It is estimated that the risk of having another child with Down syndrome is about 1 in 100 in trisomy 21 and mosaicism. If, however, the child has translocation Down syndrome and if one of the parents is a translocation carrier, then the risk of reoccurrence increases markedly. The actual risk depends on the type of translocation and whether the translocation is carried by the father or the mother.

Down syndrome consists of an extra number of the 21 chromosome. It is now known that it is not necessary for a whole additional chromosome 21 to be present to cause Down syndrome. All that is needed is for an extra amount of a critical small portion of the chromosome to be present. The rest of chromosome 21, although usually also present in excess, does not appear to play any part in producing the syndrome. This additional chromosome causes an excessive amount of certain proteins to be formed in the cell. The particular proteins involved, and how they act, are not known. Many errors can occur during cell division. In meiosis, the pairs of chromosomes are supposed to split up and go to different spots in the dividing cell; this event is called “disjunction.” However, occasionally one pair doesn’t divide, and the whole pair goes to one spot. This means that in the resulting cells, one will have 24 chromosomes and the other will have 22 chromosomes. This accident is called “nondisjunction.” If a sperm or egg with an abnormal number of chromosomes merges with a normal mate, the resulting fertilized egg will have an abnormal number of chromosomes. In Down syndrome, 95% of all cases are caused by this event: one cell has two 21st chromosomes.

Hence the scientific name, trisomy 21. . Recent research has shown that in these cases, approximately 90% of the abnormal cells are the eggs. The cause of the nondisjunction error isn’t known, but there is definitely connection with maternal age. Although it is clear that maternal age is a significant factor in causing trisomy 21, the role of the father’s age is less clear. There is conflicting evidence from studies in different parts of the world. Trisomy 21 is one of the three different types of Down syndrome and the most common. The other two are Translocation and Mosaicism

Three to four percent of all cases of trisomy 21 are due to Robertsonian Translocation. There is a presence of an extra part, rather than the whole, of chromosome 21. This occurs when the small top portions of chromosome 21 and another chromosome break off, and the two remaining portions stick to one another at their exposed ends. In translocations they have found that parental age is not a factor. In translocation only certain chromosomes become involved with chromosome 21. They are chromosomes 13,14,15, or 22, or another chromosome 21 (14 is the most common). All of these chromosomes have small, genetically inactive tips, which can break off and be lost without any ill effect. Children with translocation Down syndrome do not differ from children with trisomy 21 Down syndrome in the degree to which they are affected. The fact that children with translocation do not have the extra top part of the chromosome makes no difference, because this is not a genetically important part.

Mosaicism is in about 1 per cent of children with Down syndrome, there is an extra whole chromosome 21 in only a proportion of their body cells. These people have a mixture of cell lines, some of which have a normal set of chromosomes, and others which have trisomy 21. In cellular mosaicism, the mixture is seen in different cells of the same type. In tissue mosaicism, one set of cells, such as all blood cells, may have normal chromosomes, and another type, such as all skin cells, may have trisomy 21.

There are two types of tests available to pregnant women to test for Down syndrome. Diagnostic tests sample fetal cells and give a definitive diagnosis. Screening tests are relatively simple tests that find most of the fetuses with Down syndrome, but they also find some without. Screening tests need to be confirmed by a diagnostic test.

Diagnostic tests are amniocentesis and chorionic villus sampling (CVS). Amniocentesis is the commonest form of antenatal diagnosis for Down syndrome. With amniocentesis a needle is passed through the mother’s belly into the womb to sample fetal cells in the amniotic fluid. These cells are then sent for chromosome analysis. The result of the chromosome test becomes available about 2 weeks after amniocentesis. An ultrasound is used to safely pass the needle. The test is usually done between 14 and 18 weeks of pregnancy and is fairly safe, but there is a small risk of miscarriage. If it does happen after amniocentesis, it usually occurs two to three weeks after the event. The risk of miscarriage occurring after amniocentesis is about 1 in a 100. CVS samples cells from the chorionic villi, a structure in the womb that has fetal cells but is not the fetus. It is done between 9 and 12 weeks. Chorionic villi are made up of special rapidly dividing cells, which grow to become the placenta. Growth of these cells in the laboratory is therefore extremely quick, and it is possible for the chromosome result to be available a day or two after the procedure. It also has similar risks.

When the results of the amniocentesis or the chorionic villus biopsy show that the child has normal chromosomes, this means that neither Down syndrome nor any other major chromosomal abnormality is present. The ultrasound scan, which is performed together with these procedures, is also able to exclude certain malformations. This does not give 100 per cent assurance that the child is going to be normal.

Screening tests include maternal alpha-fetoprotein and the triple test. It is done in conjunction with amniocentesis and chorionic villus sampling. The maternal alpha-fetoprotein test was initially devised to screen for neural tube defects, such as spina bifida. A low level of alpha-fetoprotein is correlated with Down syndrome and some other chromosome disorders. The test is estimated to detect approximately 35 per cent of fetuses with Down syndrome after confirmation by amniocentesis.

The triple test measures a mother’s blood levels of human chorionic gonadotropin (hCG), maternal serum alpha-fetoprotein (MSAFP) and unconjugated estriol. The three results are adjusted by a computer program to give an estimate of the risk of having a fetus with Down syndrome. Studies so far suggest a detection rate of 55-60 per cent after confirmation by amniocentesis. Because the accuracy of all of the serum tests depends on accurately knowing the number of weeks of pregnancy, a positive test should have an ultrasound done to confirm the due date of the pregnancy. If the adjusted test results are still positive, then either amniocentesis or chorionic villus sampling should be done.

There are many heath concerns for children with Down syndrome. They are in need of the same kind of medical care as any other child. The pediatrician or family physician should provide general health maintenance, immunizations, attend to medical emergencies, and offer support and counseling to the family. There are, however, situations when children with Down syndrome need special attention.

1.60 to 80 per cent of children with Down syndrome have hearing deficits.

2.40 to 45 per cent of children with Down syndrome have congenital heart disease. Many of these children will have to undergo cardiac surgery and often will need long term care by a pediatric cardiologist.

3.Intestinal abnormalities also occur at a higher frequency in children with Down syndrome. They may need to be surgically corrected at once in order to have a normal functioning intestinal tract.

4.Children with Down syndrome often have more eye problems than other children who do not have this chromosome disorder. 3 per cent of infants with Down syndrome have cataracts.

5.Thyroid dysfunctions are more common in children with Down syndrome than in normal children. Between 15 and 20 per cent of children with Down syndrome have hypothyroidism.6.Skeletal problems are also more frequently noted in children with Down syndrome. Approximately 15 per cent of people with Down syndrome have atlantoaxial instability. Most of these individuals, however, do not have any symptoms, and only 1-2 per cent of individuals with Down syndrome have a serious neck problem that requires surgical intervention.

7.Other important medical aspects in Down syndrome, including immunologic concerns, leukemia, Alzheimer disease, seizure disorders, sleep apnea and skin disorders, may require attention of specialists in their respective fields.

Although many medications and various therapies have been touted as treatment for people with Down syndrome, there is no effective medical treatment available at the present time. However, recent advances in molecular biology make it feasible now to examine the genetic basis for Down syndrome.

Today early intervention programs, pre-school nurseries, and integrated special education strategies have demonstrated that youngsters with Down syndrome can participate in many learning experiences which can positively influence their overall functioning. Research has shown that early intervention, environmental enrichment, and assistance to the families will result in progress that is usually not achieved by those infants who have not had such educational and stimulating experiences. Children with Down syndrome, like all children, can benefit from sensory stimulation, specific exercises involving gross and fine motor activities, and instruction in cognitive development. Also, preschool nurseries play an important role in the young child’s life since exploring the environment beyond the home enables the child to participate in a broader world. Later, the school can give the child a foundation for life through the development of academic skills and physical as well as social abilities. Experiences provided in school assist the child in obtaining a feeling of self-respect and enjoyment. School should provide an opportunity for the child to engage in sharing relationships with others and help to prepare the child to become a productive citizen. Contrary to some views, all children can learn, and they will benefit from placement in a normalized setting with support as needed. During adolescence, youngsters with Down syndrome should be exposed to prevocational training in order to learn good work habits and to engage in proper relationships with co-workers. Appropriate vocational counseling and job training will result in meaningful employment, and this, in turn, should lead to a feeling of self-worth and of making a contribution to society.

The estimated incidence of Down syndrome is between 1 in 1,000 live births. Each year approximately 3,000 to 5,000 children are born with this chromosome disorder. It is believed there are about 250,000 families in the United States who are affected by Down syndrome.

Raising children these days is anything but cheap. According to an article in the March 30, 1998 issue of U.S. News & World Report, a middle income, one-child family (earning 35 K to 59.7 K a year) will spend nearly $1,000,000 on average, to raise their child to age I8. One million dollars! And that’s before college! In this same report, the total cost for 17 years of health care for an average child was estimated at $20,757, even when taking co-payments and deductibles into account. On the other hand, the lifetime health costs of a child born with Down syndrome; according to the March of Dimes in this article is $451,000 – more than 22 times the average!

Bibliography:

Bibliography Page

Books:

1.Selikowitz, Mark. (1997). Down Syndrome: the facts. New York: Oxford University Press Inc.

2.Van Dyke, D.C. M.D., Mattheis, Philip M.D., Schoon Eberly, Susan M.A., Williams, Janet R.N. (1995). Medical and Surgical Care for Children with Down Syndorme: A Guide for Parents. Bethesda: woodbine House.

Internet:

1.“Trisomy 21: The Story of Down Syndrome.” Down Syndrome: Health Issues: news and information for parents and professionals. 9 June 1997 www.ds-health.com/trisomy.htm

2.“Background Information.” Down Syndrome: understanding the gift of life. February 1995 www.nas.com/downsyn/faq1.html