DOWN'S SYNDROME (TRISOMY 21)

Ércio Filho, MD., MA in Pediatrics by the State University Rio Grande do Sul (UFRGS).

What's it?

Down's syndrome is the most common form of mental retardation caused by a microscopically demonstrable chromosomal abnormality. It's characterized by well defined phenotypic aspects and natural history. It's caused by the occurrence of a 3rd (trisomy) chromosome 21, in its entirety or a key section of it.

Clinical characteristics

Down's syndrome, a specific combination of phenotypic features that includes mental retardation and a typical face, is caused by the presence of 3 chromosomes 21 (one more than normally found , trisomy 21), and is one of the most common chromosomal anomalies among living neonates.

It's been known for a long time that the risk of having a child with trisomy 21 increases with the mother's age. For instance, the risk of having a baby with Down's syndrome, if the mother is 30 years old, is 1 in 1,000, if the mother is 40 years old, the risk is 9 in 1,000. In the general population, the frequency of Down's syndrome is 1 for every 650 to 1,000 living newborn babies, and around 85% of the cases occur to mothers aged below 35 years old.

People suffering from Down's syndrome are usually shorter and have a slower physical and mental development than those without the syndrome. Most of these people have mild to moderate mental retardation; some don't have retardation and are situated in the borderline to low average range, while others may suffer from severe mental retardation.

There's a great variation in the mental ability and developmental progress of children with Down's syndrome. The motor development of these children is also slower. While kids without the syndrome usually walk at 12 to 14 months old, the affected children, as a rule, learn how to walk at 15 to 36 months. Language development is similarly delayed.

It's important to stress that a loving and stimulating environment, early intervention and integrated educational efforts will always positively influence these children's development.

Although individuals with Down's syndrome have specific physical features, generally they have more similarities to the general population than differences. The physical features are important for a doctor to arrive at the clinical diagnosis; however, their presence have no other significance. Not always does a child with Down's syndrome have all the characteristics; some may have just a few, whereas others may show most of the syndrome signs.

Some of the physical characteristics of children with Down's syndrome are: br> 

flattening of the back of the head,
slanting of the eyelids,
small skin folds at the inner corner of the eyes,
protuberant tongue,
depressed nasal bridge,
slightly smaller ears,
small mouth,
decreased muscle tone,
loose ligaments,
small hands and feet,
excess skin in the back of the neck.

Approximately 50% of all children with Down's syndrome have a single crease across the palm of the hand (simian-like line), and there's often a larger gap between the first and the second toes. Frequently, these children present major congenital malformations.

The main malformations are found in the heart (30-40% in some studies), most notably in the atrioventricular canal, and in the gastrointestinal tract, such as duodenal atresia or stenosis, anal imperforation, and Hirschsprung disease.

Some types of leukemia and the leukemoid reaction have an increased incidence in Down's syndrome. Estimates of relative risk for leukemia have ranged from 10 to 20 times higher than in average population; acute megakariocytic leukemia, most notably, occurs in people with Down's syndrome 200 to 400 times as often as in the population with normal chromosomes. Transitory leukemoid reactions have been reported time and again in the neonatal period.

80 to 90% of the people with Down's syndrome have some sort of hearing deficiency, usually the conductive type. Patients with Down's syndrome develop neuropathological features of the Alzheimer disease at an earlier age than individuals suffering from Alzheimer without trisomy 21.

Cytogenetics

Most individuals (95%) with trisomy 21 have 3 free copies of the chromosome 21; in approximately 5% of the patients, a copy is translocated to another acrocentric chromosome, usually the chromosomes 14, 21 or 22. In 2%-4% of the cases with free trisomy 21, mosaicism is present, that is, both a cell line with trisomy and a normal cell line are available in the same individual.

Genetic counseling

Parents that have a child with Down's syndrome are at greater risk of having another child with the syndrome in future pregnancies. It's been calculated that the risk for having another child affected is nearly 1 in 100 in trisomy 21 and mosaicism. However, if the infant suffers from Down's syndrome due to translocation and if one of the parents is a translocation carrier (which happens to one third of the cases), then the risk of recurrence markedly increases. The actual risk depends on the type of translocation and whether the translocation carrier is the father or the mother.

Special cares 

Children with Down's syndrome need the same kind of clinical care any other child needs. However, there are situations that demand some special attention.
Eighty to ninety per cent of the children suffering from Down's syndrome present hearing deficiencies. Early audiologic evaluations and follow-up exams are indicated.
Thirty to forty per cent of these children have some congenital heart condition. Many of them will have to undergo heart surgery, and will often need long-term attention from a pediatric cardiologist.
Intestinal anomalies also occur with higher frequency in children with Down's syndrome. For instance, duodenal atresia or stenosis, anal imperforation, and Hirschsprung disease. These children may also need immediate surgical correction of these disorders.
Children with Down's syndrome often have more eye problems than other children. For instance, 3% of these kids suffer from cataract. They need to be surgically treated. Eye problems such as strabismus, myopia and other disorders are frequently observed in children with Down's syndrome.
Another concern is related to nutritional aspects. Some children, especially those with a severe heart condition, have constant difficulty putting on weight. On the other hand, obesity is often observed during adolescence. These conditions can be prevented through proper nutritional advise and preventive dietary counseling.
Thyroid hormone deficiencies are more common in children with Down's syndrome than in average children. 15 to 20% of the children suffering from the syndrome present hypothyroidism. It's important to identify children with Down's syndrome who have thyroid disorders, since hypothyroidism may compromise the normal functioning of the central nervous system.
Orthopedic problems are more frequently observed in children with Down's syndrome as well. Among these are included kneecap subluxation (incomplete or partial dislocation), hip luxation, and atlantoaxial instability. The latter occurs when the two first bones of the neck are not well aligned due to the presence of loose ligaments. Approximately 15% of the people with Down's syndrome have atlantoaxial instability. However, most of these individuals show no symptoms at all, and only 1-2% of the individuals with this syndrome have a neck problem severe enough to require a surgical intervention.
Further important medical aspects in Down's syndrome include immunologic disorders, leukemia, Alzheimer disease, convulsions, sleep apnea, and skin disorders. All of these may necessitate care from specialized professionals.
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