THE CHROMOSOMES
Chromosomes are thread-like structures composed of DNA and other proteins. They are present in every cell of the body and carry the genetic information needed for that cell to develop. Human cells normally have 46 chromosomes that can be arranged in 23 pairs. Of these 23, 22 are alike in males and females; these are called the “autosomes.” The 23rd pair is the sex chromosomes (‘X’ and ‘Y’). Human cells divide in two ways. The first is ordinary cell division (“mitosis”), by which the body grows.

In this method, one cell becomes two cells that have the exact same number and type of chromosomes as the parent cell. The second method of cell division occurs in the ovaries and testicles (“meiosis”) and consists of one cell splitting into two, with the resulting cells having half the number of chromosomes of the parent cell. So, normal eggs and sperm cells only have 23 chromosomes instead of 46. This is what a normal set of chromosomes looks like (fig.1). The test in which blood or skin samples are checked for the number and type of chromosomes is called a karyotype.

DOWN SYNDROME
Down syndrome, also called Trisomy 21 is the most common cause of mental retardation and malformation in a newborn.

It occurs because of the presence of an extra 21st chromosome. Each person inherits 23 chromosomes from their mother and 23 chromosomes from their father. Sometimes an accident occurs and one of the parents gives an extra chromosome.

The extra chromosome could have come from either parent – so, neither the mother nor father should carry any ‘blame’ for their child’s condition. When the extra chromosome happens to be chromosome number 21, Down syndrome occurs (fig.2).

Down Syndrome is not contagious. It is not a disease, and cannot be cured by medicine or surgery.

In Down syndrome, 95% of all cases are caused by an error called non-disjunction – one cell has two 21st chromosomes instead of one; so the resulting fertilized egg has three 21st chromosomes. Hence the scientific name, trisomy 21.

This extra 21st chromosome is either present with the 21st pair itself where the total chromosomal number is 47, or attached to the 13th, 14th, or the 15th chromosome pair where the total chromosomal number may be 46 itself. So the conditions are called pure trisomy or translocation respectively.

A condition called mosaicism exists which is due to the fact that only certain cell lines have abnormal cells and the rest do not have, for e.g., the skeletal system may have cells with trisomy-21 and the blood may have normal cells with 46 chromosomes without trisomy.

The cause of the nondisjunction error isn’t known, but there is definitely connection with maternal age. Research is currently aimed at trying to determine the cause and timing of the nondisjunction event.

• Trisomy-21
  The vast majority of children with Down syndrome (approximately 95 percent) have an extra 21 chromosome. Instead of the normal number of 46 chromosomes in each cell, the individual with Down syndrome has 47 chromosomes. These children may only have triplication of part of the 21st chromosome instead of the whole chromosome, which is called a trisomy 21.
• Translocation
  Three to four percent of all cases of trisomy 21 are due to Robertsonian Translocation. In this case, two breaks occur in separate chromosomes, usually the 14th and 21st chromosomes. There is rearrangement of the genetic material so that some of the 14th chromosome is replaced by extra 21st chromosome. The extra 21st chromosome is attached or translocated on to another chromosome, usually on chromosome 14, 21 or 22. Translocations resulting in trisomy 21 may be inherited, so it is important to check the chromosomes of the parents in these cases to see if either may be a “carrier.”
• Mosaicism
  The remainder of cases of Down syndrome (one percent) is due to mosaicism. In this case, some cells have 47 chromosomes and others have 46 (normal) chromosomes. Mosaicism is thought to be the result of an error in cell division soon after conception. 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.

The most common cause of Down syndrome occurs when an infant is born with three, rather than two, copies of the 21st chromosome (known medically as trisomy 21).

It is this extra genetic material in infants with Down syndrome that disrupts their physical and cognitive development. 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 known for some time that the risk of having a child with Down syndrome increases with advancing age of the mother; i.e., the older the mother, the greater the possibility that she may have a child with Down syndrome. However, most babies with Down syndrome (more than 85 percent) 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 from the mother or the father. Why Down syndrome occurs is a mystery. It can happen to anyone.

Although not all Down syndrome infants share the same distinguishing physical characteristics, some may have traits to a larger or lesser degree. A preliminary diagnosis can usually be made at birth just by looking at the baby. If the attending physician suspects Down syndrome, a karyotype – a blood or tissue sample stained to show chromosomes grouped by size, number, and shape – will be performed to verify the diagnosis.

The most familiar physical traits of Down syndrome include:

• Low muscle tone (muscle hypotonia)
• Flat facial profile, including a somewhat depressed nasal bridge and small nose
• Upward slant to the eyes (oblique palpebral fissures)
• Abnormal shape and small size of the ears (dysplastic ears)
• Single deep crease across the center of the palm (simian crease)
• Excessive ability to extend the joints (joint hypermobility)
• Fifth finger has one bending joint instead of two (dysplastic middle phalanx)
• Small skin folds on the inner corners of the eyes (epicanthic folds)
• Excessive space between large and second toe (sandal gap)
• Enlargement of tongue in relationship to size of mouth

Children with Down syndrome can exhibit these traits in varying degrees. In addition to the characteristics above, half of the children born with Down syndrome have congenital heart defects. The majority of these defects can be corrected, resulting in long-term health improvements.

Children with Down syndrome also tend to have increased susceptibility to infection, respiratory problems, eye problems, thyroid dysfunctions, obstructed digestive tracts (early in infancy), and childhood leukemia. Recent medical advances have made most of these health problems treatable, however, and people born with Down syndrome now have an average life expectancy of 55 years.

While children with Down syndrome continue to acquire physical and mental skills throughout their lives, their ability levels vary considerably. In general, their average rate of progress will be slower than ordinary children. Because speech may also be delayed, careful attention should be paid to a child’s hearing. Retention of fluid in the inner ear is a common cause of hearing and speech problems.

Although there is no way to prevent Down syndrome, there is less than a 1% chance (depending on the age of the mother) that parents who have a child (or other relative) with Down syndrome will have another baby with the same genetic abnormality. When there is an increased risk because of a mother’s age (35 years or older) or a history of genetic defects in a family, parents may want to use screening and diagnostic tests.

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.

R A simple, risk-free blood test that can detect Down syndrome from the blood of pregnant women has raised the prospect of screening being routinely available to every expectant mother. Researchers in Hong Kong have developed a way of identifying genetic markers, which show whether an unborn child has the chromosomal disorder, without relying on risky amniocentesis techniques. The experimental procedure has been shown to diagnose 90 per cent of Down’s syndrome cases in a small trial, while also correctly identifying 97 per cent of foetuses that do not have the condition.

Scientists hope that if the procedure can be refined and its accuracy improved, it could replace more invasive testing techniques within three to five years. The most common prenatal test for Down’s syndrome involves amniocentesis or chorionic villus sampling (CVS) in which a sample of the fluid surrounding the foetus is collected and analysed. Both procedures are invasive and and carries a one per cent risk of miscarriage. As a result, it is only usually carried out if there is a high enough risk of a disorder – in older mothers, for example.

The Non-Invasive Prenatal Diagnosis (NIPD) test would do away with these risks, but at the same time, would create an ethical dilemma for many couples following a positive result. There are fears that the new approach could ultimately lead to a greater number of abortions. Nigel Carter, of the Welcome Trust Sanger Institute, near Cambridge, whose team is working on the technique, said: “As well as your ultra-sound scan, you would have a few millilitres of blood taken for your Down’s test.”

“It’s the sort of procedure that could move from being offered only to mothers at risk, to become a more normal screening procedure,” Times Online quoted Carter, as saying. Down syndrome occurs when three copies of chromosome 21 are inherited instead of the usual two, causing learning difficulties, often accompanied by serious cardiac defects and a high risk of early-onset dementia.

The NIPD study is published in the journal Nature Medicine. (ANI)