• How is there a third copy of Chromosome 21?
• Are there different types of Down syndrome?
• Is Down syndrome inherited?
• What are the physical characteristics of Down syndrome?
• What are the medical problems associated with Down syndrome?
• What help is available for children with Down syndrome?
• Development of early communication skills in children with Down syndrome

How is there a third copy of Chromosome 21?
During cell division to create a germ cell (either sperm or egg), a cell containing 46 chromosomes divides into two germ cells each containing 23 chromosomes. Sometimes this division does not happen properly and one cell may contain 22 chromosomes and the other may contain 24 chromosomes. This can happen if the chromosomes do not properly separate and instead "stick together." This is called nondisjunction because the chromosomes have failed to disjoin or split-up. 75% of the time it is the egg cell which carries the additional chromosomal material, 25% of the time it is the sperm cell. If the cell containing 24 chromosomes combines with a cell containing 23 chromosomes, the new cell will contain 47 chromosomes instead of 46. If the trisomy is chromosome 21, the person will have Down syndrome. Other conditions arise if the duplicated chromosome is a different chromosome. If the trisomy is chromosome 13, the person will have Patau's syndrome. If the trisomy is chromosome 18, the person will have Edward's syndrome. These conditions are rarer than Down syndrome and have their own characteristics which are different than Down syndrome.

Are there different types of Down syndrome?
There are three different types of Down syndrome: Standard Trisomy 21, Translocation, and Mosaicism.

Standard Trisomy 21 is when the extra chromosome 21 comes from either the egg or sperm cell. Between 90% and 95% of all Down syndrome is Standard Trisomy 21.

Translocation is caused when a piece of chromosome 21 is located on another chromosome such as chromosome 14. The person with Translocation Trisomy 21 will have 46 chromosomes but will have the genetic material of 47 chromosomes. The person with Translocation Trisomy 21 will exhibit all the same characteristics of a person with Standard Trisomy 21 since they have three copies of chromosome 21. Translocation occurs between 3% and 5% of cases of Down syndrome.

Mosaicism is when a person has a mix of cells, some containing 46 chromosomes and some containing 47 chromosomes. This occurs either because: a) The person received 46 chromosomes at fertilization but somewhere during early cell division the chromosome 21 cell pairs failed to split creating a cell with 47 chromosomes and a cell with 45 chromosomes. The cell with 45 chromosomes can not survive but the cell with 47 chromosomes will continue to divide. All cells that come from this cell will contain 47 chromosomes. b) The person received 47 chromosomes at fertilization but later during cell division the extra chromosome is lost. Mosaicism occurs in 2% to 5% of cases of Down syndrome. A person with Mosaic Down syndrome may exhibit all, some, or none of the characteristics of Down syndrome depending on the percent of cells carrying the extra chromosome and where these cells are located.

Is Down syndrome inherited?
The vast majority of cases of Down syndrome are not inherited. Only in cases of Translocation Down syndrome and then in only 1 of 3 cases of this type of Down syndrome is the condition inherited. These inherited cases occur because one of the parents is a carrier. A carrier will have 45 chromosomes instead of 46 but they will have all the genetic material of a person with 46 chromosomes. Remember that in Translocation Down syndrome the extra chromosome 21 material is located on a different chromosome. A carrier will have the extra material but will have only one chromosome 21. The carrier will not exhibit any of the symptoms of Down syndrome because they have the correct amount of genetic material.

A carrier will have an increased chance of having a child with Down syndrome. If the carrier is the mother, the chances are approximately one in five of having a child with Translocation Down syndrome. If the carrier is the father the odds are reduced to between one in twenty to fifty. In cases where the carrier has no unattached chromosome 21, all the carriers children will have Down syndrome. In all cases of Down syndrome but especially in cases of Translocation Down syndrome, it is important that the parents have genetic counseling to determine their risk.

What are the physical characteristics of Down syndrome?
Many babies with Down syndrome have certain physical characteristics which are common in Down syndrome. These signs occur in up to 80% of all cases. Individual characteristics are often found in children without Down syndrome but the Down syndrome child will have several. These traits are:

• The eyes have an upward and outward slant
• There is a fold of skin on the inner side of the eye (epicanthal fold)
• The eye slit is narrow and short
• Small, white patches can be seen on the edge of the iris
• The face has a flat appearance
• The head is smaller than average
• The soft spots on the head (fontanels) are larger than normal because the baby is growing more slowly
• The ears are smaller and lower-set
• The mouth is small and the lips are thin which leads to the tongue sticking out because the inside of the mouth is smaller
• The neck appears slightly short and loose folds of skin are seen at the back and sides (these go away as the baby grows)
• The legs and arms are short in relation to the body
• The hands are broad and flat with short fingers, the little finger slants inward, and there is a single crease across the palm
• The feet are broad with short toes and there is a larger space than normal between the big toe and the other toes
• There is poor muscle tone (hypotonia) and loose-jointedness (hyperflexibility)
• Reflexes tend to be weaker and the cry is weak

What are the medical problems associated with Down syndrome?
Children with Down syndrome are at an increased risk for a wide range of medical problems. These potential problems include congenital heart defects, increased susceptibility to infection, respiratory problems, gastrointestinal disorders, and childhood leukemia. However, not every baby with Down syndrome develops health problems and most of these health problems are now treatable.

Congenital heart defects:   A congenital heart defect is a heart problem that is present at birth. Between 30 and 45 percent of babies with Down syndrome are born with heart defects. These defects vary from mild defects which may disappear with time to severe defects which will require major surgery. In most cases a cardiologist can detect a heart defect soon after birth. The most common congenital heart defect is Atrioventricular (AV) septal defect. This problem occurs when the valves separating the atrium (upper chamber of the heart) from the ventricle (lower chamber of the heart) leak allowing blood to flow in the wrong direction. This problem is quite serious but can be corrected with surgery in infancy. The second most common problem is a hole in the wall of either the ventricles (Ventricular Septal Defect or VSD) or between the atrium (Atrial Septal Defect or ASD). Small holes do not cause any strain on the baby and often close by themselves. Larger holes may require surgery.

Babies with heart defects sometimes show symptoms. These symptoms can include feeding problems, a change in color during feeding, poor growth, and labored breathing.

Endocrine problems: The endocrine system is made up of the glands that produce and secrete hormones. These include the thyroid, the pituitary gland, the adrenal glands, the pancreas and many others. The most common endocrine problem in children with Down syndrome involves the thyroid. The most common type of thyroid problem both among the general population and children with Down syndrome is hypothyroidism i.e. insufficient amounts of hormones produced by the thyroid. Untreated, hypothyroidism can lead to slow growth, skin disorders, blood disorders, sleep disorders, learning disorders, and feeding disorders. Fortunately, hypothyroidism can be easily treated with an oral medication, L-thyroxine.

Hyperthyroidism is a condition where the thyroid produces too much thyroid hormone. One form of this condition is Graves disease. Symptoms include nervousness, irritability, increased appetite, increased perspiration, disturbed sleep and an enlarged thyroid. This condition is treated with medication to block the production of thyroid hormone. In some cases the thyroid may be removed or destroyed with radioactive iodine. In this case, L-thyroxine would be used to replace the thyroid hormones.

Children with Down syndrome may have a shortage of growth hormone (hGH) which is produced in the pituitary gland. hGH replacement is fairly controversial, but a child with reduced levels of hGH may be a candidate for hGH replacement therapy. It is quite common for children with genetic disorders such as Down syndrome to be short in stature and special growth charts have been developed for children with Down syndrome. However, some doctors have come to believe that children with Down syndrome should be charted on the normal growth charts. If a child fails to grow on these charts, it may be a sign that there is an endocrine problem such as hypothyroidism or hypopituitarism.

Skin problems: Infants with Down syndrome tend to have very soft skin but as they grow older their skin can become dry and coarse. A common problem for children with Down syndrome is atopic dermatitis (also called atopic eczema). This is a condition where the child has a dry, red, and scaly rash usually on the cheeks, arms, legs, or trunk. This condition is actually found in up to 10% of all children but is more common in children with Down syndrome. No permanent cure exists but the condition can be controlled. The skin should be treated with moisturizers and mild soaps or soap-free cleansers (such as Cetaphil) should be used to clean the skin. More severe cases should be treated by a dermatologist who can prescribe topical corticosteroids. Some parents have reported successfully treating atopic dermatitis by eliminating dairy and gluten (found in wheat) products from the diet.

Alopecia Areata (AA) is an autoimmune disease involving the hair and nails. Although rare, it does tend to occur more often in people with Down syndrome. It is believed that AA is an autoimmune reaction where the body attacks its own hair follicles. A person with AA usually develops bald patches although generalized thinning or complete baldness may also occur. In most cases, children with AA may have a few small patches that disappear without treatment within one year. AA can be treated with topical steroids or topical irritants but in young children these treatments are usually not practical.

Gastrointestinal problems: The gastrointestinal (GI) tract consists of the parts of the body that take in food, extract the nutrients, and dispose of the waste. Gastrointestinal problems tend to be more common in children with Down syndrome than in the normal population, however most of these conditions are rare. Gastrointestinal problems fall into two basic area:

1. anatomical anomalies - the structure of the organs is abnormal
   • aganglionic megacolon - Also called Hirschsprung's disease, this is a condition where parts of the bowel have no nerve cells. Children with this condition can become extremely constipated. Severe cases can be life threatening if left untreated. Hirschsprung's is normally treated by surgically removing the part of the bowel that does not function correctly.
   • annular pancreas - This is a condition in which the pancreas is ring-shaped and constricts part of the intestine. Depending on the amount of constriction, this can be a serious medical emergency. This condition is normally treated surgically.
   • duodenal atresia and duodenal stenosis - Both of these conditions involve a narrowing of the small intestine the difference being the amount of the narrowing. In duodenal atresia, the first part of the intestine where it connects to the stomach is completely blocked off. Since no food can pass from the stomach into the intestines, this condition must be treated immediately by surgically removing the blocked part of the intestine. A duodenal stenosis involves a narrowing of the intestine. Depending on the amount of narrowing, surgery may be required. In less serious cases, the condition may be managed through diet.
   • imperforate anus - This is a condition in which the anus (the external opening of the colon) is blocked. This condition is normally treated with surgery within the first few days after the baby is born.
   • tracheo-esophageal fistula - This is a condition where there is an opening between the windpipe and the esophagus. Some children have this condition without developing any problems. Others may require surgery to close the fistula to prevent fluids from travelling from the esophagus into the trachea.
   • pyloric stenosis - This is a narrowing of the pylorus, the junction where the stomach empties into the small intestine. This is treated with a simple surgical procedure that usually works very well.
2. functional disorders - the organs do not work the way they should
   • esophageal motility disorders and gastro-esophogeal reflux. Children with Down syndrome often have problems with reflux. Reflux does not mean that the child spits up during or after a feeding. In most cases, this simply means the child has swallowed air. Reflux can occur because the esophagus is having trouble propelling food into the stomach or it may occur because the stomach is emptying too slowly. Persistent reflux may cause serious problems since the stomach contents are highly acidic and can damage the esophagus, larynx, or trachea. If the child aspirates stomach acids, they may gag or cough just after feeding. Reflux is normally treated with medicines to reduce stomach acidity and to help move food through the stomach faster. In many cases, the child may grow out of the problem.
   • malabsorption disorders - Children with Down syndrome sometimes have a condition called celiac disease in which the intestines lose the ability to absorb nutrients. This condition is normally treated by eliminating gluten from the diet. There are other malabsorption disorders but children with Down syndrome are no more likely to have these conditions then the rest of the population. Some children with Down syndrome may have trouble absorbing certain vitamins. If the child is not growing well or has an increased number of ordinary infections that are difficult to cure, they may have a vitamin absorption problem. A blood test can help to determine if this is a problem.

What help is available for children with Down syndrome?
Depending on the programs available in your area and the specific needs of your baby, you may work with some or all of the following professionals:

• A Developmental Pediatrician is a doctor with specialized training in childhood development.
• An Infant Educator is a teacher trained to work on your child's cognitive ability. The Infant Educator will focus her attention on your baby's development and determine if that development is proceeding typically. Areas of concentration for the Infant Educator might be responsiveness to stimulation, social development, and ability to understand concepts. The Infant Educator may work with you to help you learn the techniques to improve your baby's abilities.
• A Physical Therapist will work on improving your baby's gross motor skills. She will be concerned with muscle tone, reflexes, stability, and motor development.
• An Occupational Therapist concentrates on fine motor skills. She will be concerned with your baby's ability to reach and hold objects. The Occupational Therapist will also be concerned with your baby's processing of information through vision, touch, hearing, and movement.
• A Speech Therapist will concentrate on how your baby uses the muscles of the mouth and face to eat and to make sounds. The Speech Therapist can be a resource for problems dealing with feeding. As your baby grows, the Speech Therapist will help your baby properly make sounds and words.
• Mental Health Professionals include social workers, counsellors, and others who can provide counselling and emotional support to your family. Many early intervention programs include parent support groups which give parents an opportunity to share information and seek advice from other parents.

Development of early communication skills in children with Down syndrome

Credits:

• Thomas & Michel Paul
• Kumin, L. (2003) Early Communication Skills for Children with Down Syndrome - A Guide for Parents and Professionals, Woodbine House, MD