Overdose of chromosome 21

Down syndrome is the commonest chromosome abnormality in humans, but early interventions can improve physical and mental disabilities:

World Down Syndrome (DS) Day was observed recently. Apart from the delay in cognitive ability (mental retardation) and physical growth that usually occur as a result of DS, which begins in early childhood, the disease also adversely affects the bones and joints, hampering the movements of the child. These negative impacts however can be largely reduced with early interventions.

Chartered Physiotherapist, Dr Gopi Kitnasamy, explains how the disease is caused and why early physiotherapy should be initiated.

Excerpts…

A: Down Syndrome (DS) or Down’s syndrome, also known as trisomy 21, is a chromosomal condition caused by the presence of all or part of a third copy of chromosome 21. Down syndrome is the most common chromosome abnormality in humans. This extra chromosome changes the normal development of the body and brain. It is typically associated with a delay in cognitive ability (mental retardation, or MR) and physical growth, and a particular set of facial characteristics. Almost all of the conditions that affect the bones and joints of people with Down syndrome arise from the abnormal collagen found in Down syndrome. Collagen is the major protein that makes up ligaments, tendons, cartilage, bone and the support structure of the skin. One of the types of collagen (type VI) is encoded by a gene found on the 21chromosome. The resulting effect in people with DS is increased laxity, or looseness, of the ligaments that attach bone to bone and muscle to bone.

The combination of this ligamentous laxity and low muscle tone contribute to orthopedic problems in people with Down syndrome. Motor function in individuals with Down syndrome is characterised by hypotonia and hyperflexibility, which results in an increased risk of joint dislocation and retarded motor skills. Hypotonia, decreased muscle tone, has a negative effect on the proprioceptive feedback from muscle and joint sensory structures and can have a detrimental effect on the efficiency of co-contractions and postural reactions. People with Down syndrome have more joint mobility than the average. The enlarged joint mobility may contribute to the lack of posture control. Together with the failure of co – contraction, it will affect the joint stability.

Q: You referred to several musculoskeletal problems that persons with DS are likely to suffer from. What are the most common and which part of the body is most affected?

*Spine - Atlantoaxial instability, which is the looseness between the first and second vertebrae of the neck.

* Hip - five to eight percent of children with DS will develop abnormalities of the hip. With regard to the hip, the most common condition is dislocation of the hip, which is also called subluxation. In this condition, the head of the thigh bone (the femur) moves out of the socket formed by the pelvis (the acetabulum). This dislocation may or may not be associated with malformation of the acetabulum. The dislocation appears to be due to a combination of laxity of the connective tissue that normally keeps the hip together along with the low muscle tone found in DS.

What Causes Down Syndrome?

The cause of the extra full or partial chromosome is still unknown. Maternal age is the only factor that has been linked to an increased chance of having a baby with Down syndrome resulting from nondisjunction or mosaicism. However, due to higher birth rates in younger women, 80% of children with Down syndrome are born to women under 35 years of age.

There is no definitive scientific research that indicates that Down syndrome is caused by environmental factors or the parents’ activities before or during pregnancy. The additional partial or full copy of the 21st chromosome which causes Down syndrome can originate from either the father or the mother. Approximately 5% of the cases have been traced to the father.

What is the likelihood of having a child with Down syndrome?

Down syndrome occurs in people of all races and economic levels, though older women have an increased chance of having a child with Down syndrome. A 35 year old woman has about a one in 350 chance of conceiving a child with Down syndrome, and this chance increases gradually to 1 in 100 by age 40. At age 45 the incidence becomes approximately 1 in 30. The age of the mother does not seem to be linked to the risk of translocation.

Does down syndrome run in families?

All 3 types of Down syndrome are genetic conditions but only 1% of all cases of Down syndrome have a hereditary component. Heredity is not a factor in trisomy 21 (nondisjunction) and mosaicism. However, in one third of cases of Down syndrome resulting from translocation there is a hereditary component - accounting for about 1% of all cases of Down syndrome.

How is Down syndrome diagnosed?
Prenatally

There are two categories of tests for Down syndrome that can be performed before a baby is born: screening tests and diagnostic tests. Prenatal screens estimate the chance of the fetus having Down syndrome. These tests do not tell you for sure whether your fetus has Down syndrome; they only provide a probability. Diagnostic tests, on the other hand, can provide a definitive diagnosis with almost 100% accuracy.

At Birth

Down syndrome is usually identified at birth by the presence of certain physical traits: low muscle tone, a single deep crease across the palm of the hand, a slightly flattened facial profile and an upward slant to the eyes. Because these features may be present in babies without Down syndrome, a chromosomal analysis called a karyotype is done to confirm the diagnosis. Another genetic test called FISH can apply similar principles and confirm a diagnosis in a shorter amount of time.

A: Interestingly, hip subluxation in children with Down syndrome is hardly ever found at birth but instead is most common between the ages of 3 and 13 years. The most common sign is a limp, and pain may or may not be present.

* Knee - Instability of the patella (kneecap) has been estimated to occur in close to 20 per cent of people with DS. The majority of cases of instability present only as kneecaps that can be moved further to the outside than the normal kneecap (subluxation); however, some people can have their kneecaps completely move out of position (dislocation), and some may even have a hard time getting it back into the right position. Mild subluxation of the kneecap is not associated with pain, but dislocation may be painful. While people with instability of the patella are able to walk, there is often a decreased range of motion of the knee, with an accompanying change in gait. The longer nothing is done for the instability, the worse the condition will get over time.

Detected at birth

A consultant neurologist speaking in a telephone interview on grounds of anonymity said Down Syndrome is usually detected at birth, going on the physical appearance of the child, with older mothers being more at risk of giving birth to such children. Once a child has been diagnosed with DS, parents should not adopt a negative attitude. “Rather, they should seek early advice on how they can help them to develop. If exposed to stimulation at a younger age, the better the outcome for the child. The important thing is for parents to seek professional advice like occupational therapy and interact with their children at all stages of their development, however slow. They must continue to do this and watch their improvements however small,” the neurologist emphasised.

*Foot - Flat foot, also called ‘pes planus’, is seen in the vast majority of people with DS. In mild cases, the heel is in a neutral position. In severe cases, the heel rotates so that the person is walking on the inside of the heel.

* Metatarsus primus varus is also commonly seen in people with DS. This is a condition in which the front part of the foot behind the big toe bends inward.

A: The goal of physiotherapy for children with DS is not to accelerate their rate of gross motor development as is commonly assumed. The goal is to improve the near normal gross motor development and minimise the development of abnormal compensatory movement and posture patterns that children with DS are prone to develop. Early physiotherapy makes a decisive difference in the long-term functional outcome of the child with DS. The gross motor development is the first learning task that the child with DS encounters; it provides parents with the first opportunity to explore how their child learns. There is increasing evidence that the children with DS have a unique learning style.

A: Understanding how children with DS learn is crucial for parents who wish to facilitate the development of gross motor skills as well as facilitating success in other areas of life including language, education and the development of social skills.

Normal gait or walking is very important. Ligamentous laxity, hypotonia and weakness in the legs lead to lower extremity posturing with hip abduction and external rotation, hyperextension of the knees and pronation and eversion of the feet. Children with DS typically learn to walk with their feet wide apart, their knees stiff and their feet turned out.

They do so because hypotonia, ligamentous laxity and weakness make their legs less stable. Locking their knees, widening their base and rotating their feet outward are all strategies to increase stability. The problem however is that this is an inefficient gait pattern for walking. The weight is being borne on the medial (inside) borders of the feet, and the feet are designed to have the weight borne on the outside borders. If this pattern is allowed to continue, problems will develop with both the knees and the feet. Walking will become painful, and endurance will be decreased. Physiotherapy should begin teaching the child with DS the proper standing posture (i.e., feet positioned under the hips and pointing straight ahead with a slight bend in the knees) when he or she is still very young. With appropriate Physiotherapy, gait problems can be minimised or avoided.

Trunk position or spinal posture is another important consideration for physiotherapy. Ligamentous laxity, hypotonia and decreased strength in the trunk encourage the development of kyphosis or Scoliosis, which is often first seen when the child is learning to sit. Children with DS typically learn to sit with a posterior pelvic tilt, trunk rounded and the head resting back on the shoulders. They never learn to actively move their pelvis into a vertical (upright) position, and therefore, cannot hold their head and trunk over it. If this posture is allowed to persist, it will ultimately result in impaired breathing and a decreased ability to rotate the trunk.

The other important goal is to facilitate the development of optimal motor movement patterns. Children often develop adaptations that help them achieve movement but can lead to musculoskeletal injuries over the long term. Physiotherapy helps prevent these non-ideal patterns from developing and prevent developing other musculoskeletal problems.