Brandon Hescox
Biology 222W - Genetics
Printed with the permission of Jeffrey D. Newman
Biology Department, Lycoming College
Williamsport PA 17701
(570) 321-4386
Fax: (570) 321-4073

Down syndrome, the most common genetic birth defect associated with mental retardation, occurs equally across all races and levels of society. The effects of the disorder on physical and mental development are severe and are expressed throughout the life span. The individual's family is also affected emotionally, economically, and socially (Bellenir 1996).

Characteristics associated with Down syndrome include: epicanthal folds, unilateral squints, a flat saddle nose, flat jaw bones, large fissured tongue (macroglossia), hyptonic lower lip (cheilosis), receding chin (microgenia), protruding flat ears, dry and cracked lips, dry skin, delays in skeletal maturation, shorter than average stature, delays in motor skill acquisition, flat feet, intellectual disability, delayed language abilities, and numerous others (Whitaker 1998).

It has only been known since as recently as 1959 that Down syndrome, first described in 1866 by Langdon Down, is caused by extra genetic material carried on the 21st chromosome. All normal cells in the human body, except for eggs and sperm cells, have 46 chromosomes. These being 44 autosomes and two sex chromosomes. Normal reproductive cells contain one half of that number- 22 autosomes and one sex chromosome.


The genetic effect associated with Down syndrome is the presence of extra material on the chromosome pair 21. This extra material in chromosome pair 21 is usually another chromosome. This is called Trisomy 21 (see figure 1). It occurs in 95% of all Down syndrome cases. Trisomy 21 results from as error in cell division during the development of the egg or sperm, or during fertilization (Bellenir 1996).

Translocation is an interchange of chromosomes or parts of chromosomes which may result in a mismatched pair. Translocation occurs in about four percent of the cases. Children with translocation Down syndrome have an extra number 21 chromosome that has broken and become attached to another chromosome (Bellenir 1996). In a few cases, a person can carry a broken chromosome 21 without showing any symptoms of Down syndrome because the correct amount of genetic material is present, just out of place.

Accounting for about one percent of the cases of Down syndrome is mosaicism. Affected persons have cells with different chromosome counts (for example, 46 in some cells and 47 in others) (Bellenir 1996). Essentially this is a fraction of an extra chromosome 21 attached to one of the existing chromosomes. Mosaicism is not carried in the parents' chromosomes; it is accidental, resulting from an error in cell division of the fertilized egg. Being that only some of their cells have an abnormal number of chromosomes, babies with mosaic Down syndrome may have only some of the features of the disorder.

Although surveys are all different the incidence of Down syndrome is around 1 in 800 live births. However, the risk of bearing a child with the disorder increases dramatically with advancing maternal age. For example, the incidence is less than one in 1,000 live births to women under 30, increasing to one in 35 to mothers aged 44.

Below is a table of the relationship between mothers age to the incidence of Down syndrome. It was taken from the Genetic Disorders Source Book.

 Mother's age   Incidence of Down syndrome   Mother's age   Incidence of Down syndrome 
under 30 less than 1 in 1000 39 1 in 135
30 1 in 900 40 1 in 105
35 1 in 400 42 1 in 60
36 1 in 300 44 1 in 35
37 1 in 230 46 1 in 20
38 1 in 180 48 1 in 12

The sharp rise in the incidence of babies with Down syndrome born to older women may occur for several reasons. Although males produce new sperm continually, women are born with all the oocytes they will ever have. An oocyte remains in a state of incomplete development until the process begins that results in ovulation. Thus, a 35-year-old woman has 35-year-old oocytes (Bellenir 1996).

Many body functions decline with age, and oocytes in the older woman simply may be past their prime. Or they may have been exposed through the years to damaging internal and external influences, including medications, radiation or other harmful agents.

Until recently, the mother was believed to be the source of the extra genetic material. However, new laboratory techniques, have demonstrated that in about 25 percent of the studied, the father is the source of the extra chromosome. Because older fathers have been associated with increased incidence of other genetic disorders, researchers are looking more closely at the possible effect of the father's age on the incidence of Down syndrome. In one project, involving only a small number of cases, a paternal age effect for fathers over 55 was reported (Bellenir 1996).

In most cases, the first medical exam identifies the newborn with Down syndrome. Expecting a normal infant, most parents are intensely disappointed when the physician explains their new baby's condition to them. Parents generally experience an initial period of shock, follows by denial, grief, anger, adjustment and finally acceptance. Faced with an abrupt change in their hopes and plans for the child, parents need early counseling and guidance to help the cope with the situation and plan for their child's future.

The presence of a retarded child in the home is not necessarily detrimental to the happiness and welfare of siblings or to the family as a whole. With professional guidance, and accepting community attitude and the help of parent support organizations, a loving home atmosphere can evolve. All children, but especially those with Down syndrome, benefit from loving and caring homes.

Since stereotypes of Down syndrome persist, early and sound information for new parents and other family members is very important. In the past, most physicians recommended placing the infant in an institution immediately upon discharge from the hospital nursery (Bellenir 1996). New developments in care and treatment mow permit other courses, but, unfortunately, parents are mot always made aware of these approaches or to other alternatives to institutionalization, such as the parents raising the child.

There are several techniques for the early detection of the disease in fetuses. The newest being an fetal nuchal translucency test, which is done using ultra sound. Modern ultrasound imaging can identify and measure small subcutaneous collections of fluid behind the necks and backs of fetuses during the late first trimester. Several reports link the increased thickness of such "fetal nuchal translucency" with chromosomal abnormalities (Neilson 1997). Amniocentesis is another way to test for Down syndrome. It is performed by piercing the amniotic sac and drawing out some of the fluid surrounding the baby. Amniocentesis offers mos patients 11-14 weeks LMP with 99 percent detection by acetalcholinestrase (AchE) testing.

Health and developmental problems occur in the child during the first years of life, close monitoring is necessary throughout this period. Medical management and surgical correction, when indicated, of the life-threatening congenital defects frequently associated with Down syndrome are essential to assure the child's optimal health and well-being.

Children with Down syndrome are more susceptible to infections than normal children and, as a result often suffer chronic respiratory infection, recurrent pneumonia and repeated bouts of tonsillitis. Researchers believe that children have a deficient immune response. According to several studies, they not only have fewer of the cells needed for normal immunologic response to infection, but the cells they have do not function well (Bellenir 1996).

Development delays are evident from the early months of life. Infants are slow to turn over, sit stand, speak and respond. This may be due to the mental retardation caused by the disease. Studies on infants with Down syndrome show that the brain is virtually normal size and structure for at least a few months after birth. Infants with the disease later become retarded, largely because of the over-expression of the gene for the enzyme, Superoxide dismutase (SOD). The result of this over expression is the production of excess hydrogen peroxide, a known cellular toxin that causes progressive cell damage (Whitaker 1997). It is widely accepted that a major disruption of the body's free radical defense system that results in excess production of potent free radicals such as H2O2 would cause generalized progressive cellular damage resulting in both mental and physical disability (Whitaker 1997).

Hearing loss occurs more frequently among individuals with Down syndrome than in the normal population. Because affected persons are particularly vulnerable to deficiencies in speech and language development, careful screening and testing for hearing loss should be done and corrective procedures started as early as possible.

Compared with early delay in postural-motor development (sitting, standing, walking), the delay in speech an language development encountered by the child with Down syndrome is more noticeable. In addition, beginning in the second year of life, there is an apparent decline in intelligence because language and speech become increasingly more important in intelligence tests (Bellenir 1996).

The reasons for the special difficulty that Down syndrome children have in speech and language are not fully understood. Part of the difficulty stems from the characteristic overlarge and protruding tongue, and in some instanced surgical correction of this condition has been helpful. The acquisition of speech and language also depends upon the patterns of vocal and verbal interactions between child and parents.

There is no set regimen of medicines that can prevent or reverse the effects of Down syndrome. The use of exogenous antioxidants, Vitamin A, E, C, selenium, etc., can protect against damage and literally prevent much of the disability that would be expected to result from it. Preventing this damage may indeed mean that a child will be healthier, grow at a more normal rate, and have higher mental function (Whitaker 1997).

The retardation of the brain can cause many problems. The dendrites are often broken off near the body of the neuron cell, inhibiting and changing both the flow and form of transmitted messages. People suffering from this disease may have to deal with Epilepsy in their middle ages. Epilepsy occurs in about two percent of people with Down syndrome under the age of 20 years, but rises to about 12 percent in those aged over 55 years. The thyroid gland produces a number of hormones. These control the rate of body metabolism, assist with never cell activity and are essential to normal body growth. An under active Thyroid gland can lead to loss of energy, weight gain, reduced body growth and impaired intellectual abilities. Thyroid hormones are essential for normal growth. Thyroid disease is common in about 40 percent of people with Down syndrome (Martin 1997).

As many as 80 percent of people with Down syndrome may have a hearing loss which can affect language and speech development as well as academic progress. Some of the problems which contribute to the hearing problems include a smaller pinna of the inner ear and a flattened ear which does not catch sound effectively. The outer ear may often have narrower canals which are easily blocked by dry skin or wax.

Not all families have easy access to specialized resources for their handicapped child. In these situations, efforts have focused on enhancing the ability of parents to teach their children speech, language, self-help, and social skills through home-based programs.

If effective early intervention programs can be designed and used in the preschool years, the subsequent educational progress of a child with Down syndrome may be altered significantly. A child may be classified as educable, rather than trainable, and therefor qualified for different educational opportunities and strategies.

An "educable" person is defined as one who is capable of learning such basic skills as skills as reading and arithmetic. Although trainable (moderately retarded) persons are very limited in educational attainments, they can profit from simple training for self care and vocational tasks (Bellenir 1996).

Under Public Law 94-12, each state is required to have a goal that "all handicapped children have available to them ...a free public education and related services designed to meet their unique needs." (Bellenir 1996). This means that all Down syndrome children are given the right to start in a public elementary school. The educable are main streamed into class with the other children, while those who are more limited in their abilities are taught just basic skill for life. In this there are no grade levels or individual grades given. Here they first start to interact socially with other handicapped children.

At adolescence, children with Down syndrome tend to be over weight. This may be due to general body type, lack of physical activity associated with social isolation and reduced outlets for activity, and excessive eating of high calorie foods. A supervised regimen of diet and exercise throughout this period will have a beneficial effect.

Parental concern for the social and sexual life of their child with Down syndrome usually intensifies at adolescence. Unless earlier efforts have been highly successful, the child's social isolation increases outside of structured school and other group situations. Although persons with Down syndrome seldom reproduce, it is necessary to provide them with a healthy understanding and orientation toward sexuality. Pregnancy has been rare, probably as a result of sexual isolation in institutions, but sometimes does occur. About half the infants born of such pregnancies have Down syndrome. Males with trisomy 21 not associated with mosaicism or translation have not been known to reproduce (Bellenir 1996).

For almost a century, researchers have observed that individuals born with Down syndrome tend to age prematurely. This phenomenon has become more apparent with the increased longevity of affected persons. Because intellectual deterioration is more difficult to assess in retarded individuals, the judgment of premature ageing in those with Down syndrome is based on the emotional deterioration shown in behavior.

An increased number of adults with Down syndrome are living in our communities and seeking health care from physicians. For patients to be enrolled in a medical practice, guardianship status should be determined. These patients should be involved in there own care to as great an extent as possible.

Many health problem arise for adults with Down syndrome. Their medical bills are typically taken care of by the government's Medicaid. Below is a list of special health problems and their incidence for adults with Down syndrome taken from an article on caring for adult who are mentally retarded by Barry Martin.

Health Issue Incidence
Alzheimer's Disease   almost 100% in those over 40 
Deafness 75%
Eye disease 60%
Serious otitis media 50 to 70%
 Congenital heart disease  50%
Psychiatric disorders 22%
Thyroid disease 15%
Atlantoaxial instability 14 to 22%
Seizure disorders 12 to 50%
Gastrointestinal atresia 12%
Acquired hip dislocation 6%
Hirschsprung's disease 1%

As indicated in the chart above Alzheimer's disease is a major problem for adults with Down syndrome over forty years of age. A recent test done showed that this is caused by significantly lower levels of glucose metabolite in the parietal and temporal areas. Abnormalities in cerebral metabolism during stimulation appeared in the first cortical regions typically affected in Alzheimer's disease. (Pietrini et al.).


Bellenir, Karen, ed. 1996 Genetics disorders source book. pp. 1-12 Detroit, MI: Omnigraphics

Martin, Barry A. Primary care of adults with mental retardation living in the community. American Family Physician, 1997 v.56, n.2, pp. 485(10)

Neilson, J.P. Assessment on fetal nuchal translucency test for Down's syndrome. Lancet. 1997 350(9080), pp.754-755.

Pietini, Pietro, Low glucose metabolism during brain stimulation in older Down syndrome subjects at risk for Alzheimer's disease prior to dementia. American Journal of Psychiatry. 1997 v.154, n.8, pp.1063(7).

Whitaker, Julian M.D. Down syndrome and nutritional supplements choosing the right one for your child. Health and Healing. June 1997.