This might be the most widely known genetic disorder of all. All of us know of some people living with Down syndrome.
Down syndrome is the most frequent of congenital multiple disorders compatible with life, the leading symptoms of which are anatomical defects affecting several organs and mental handicap of varying degree.
Geneticaly we differentiate three basic types: in addition to types caused by extra copies of chromosome 21 in every cell (trisomy 21), and ones caused by the presence of only extra parts of chromosome 21 (translocation), there are ones caused by so-called mosaicism (2.4%), where mutation (changes in gene pool) occur in course of the multiplication of cells, thus causing the presence of healthy and mutant cells in the same organization.
Symptoms: mental handicap, low height, obesity, underdeveloped testicles, decreased muscle tone, open mouth, protruding tongue, excessive joint flexibility, round head, mild small headedness, slanted eyes, small penis.
In Hungary, Down syndrome occurs in about 1 case out of 1000 pregnancies (1.17 per mil). Its rate of occurance has not been impacted by even the gravest global environmental catastrophies (eg. the nuclear disasters of Hiroshima, Nagasaki or Chernobil). However, the age of the mother is clearly a factor. The occurrence rate among young mothers is approximately 1/1500 pregnancies, while at the age of 40, it reaches 1/50 (2%), which rate increases by 1% by each additional year. At the age of 46, for example, risk of occurrence is 6%.
For us to understand the genetic background of Down syndrome, we need to recall the basics of chromosomes. Our cells contain 23 pairs of chromosomes, i.e. 46 chromosomes. We inherit 23 chromosomes from each parent. That is possible in a way that when sexual reproductive cells evolve a cell division process called meiosis takes place that cuts the number of chromosomes in half, so reproductive cells do not contain chromosome pairs. When ova and sperm cells fuse, they create a cell that again contains chromosome pairs: so half of genetic information is inherited from the father, the other half from the mother. In course of the division of that, the genetic pool does not change.
An overwhelming majority of Down syndrome cases (94%) are of the trisomy type, caused by a so-called non-disjuctio occurring in course of the meiosis of the sexual reproductive cells of one of the parents, i.e. when chromose pair 21 does not split, thus creating a cell that has two chromosome 21s and another one with none. out of the two defective sexual reproductive cells, the one without chromosome 21 cannot survive, thus it does not lead to a defective offspring. However, when a reproductive cell with an extra chromose 21 fuses with its counterpart, they constitute a cell containing 47 chromosomes, including three 21s, thus every cell of the child will contain 47 chromosomes.
Causes are unknown. The current hypothesis is that egg cells get old, while sperm always regenerate. Egg cells are assumed to be always the same age as the mother, including the earliest embryonic stages of the mother’s life. Even 3-month-old embrios contain all the egg cells (app. 1 million), which can be the basis for later reproduction. Later, the number of egg cells decreases, at birth, there are “only” about 300000. That is how egg cells may get old by the age of 40.
The other type is the so-called translocation, which occurs in 3-4% of all cases. This structural disorder is caused by a part of a chromosome 21 getting split from the chromosome (deletion), then attaches to another chromosome (translocation). As the chromosome set of every bodily cell is complete, this disorder does not cause any symptoms for the parent. The parent carries a so-called balanced translocation, but can hand down to the child a translocation form that causes Down syndrome. The risk of the offspring depends then on the type of structural damage and whther it is the mother or the father that carries it. Translocation may occur as a newly formed mutation, but can also be inherited from a parent carrying a balanced chromosome disorder.
The symptoms of Down syndrome are so typical that diagnosis can be established based on clinical signs only.
However, it is important that trisomy and translocation types cannot be differentiated based on clinical symptoms.
The most general symptoms include overall weak muscle tone, frequently open mouth, protruding tongue, very loose joints, low body height, clumsy movements.
Adults are often obese. The head is round, the back of the neck is flat, and the head is slightly small. The neck is shorter than usual. Skull bones are thinner, fonticuli are slow to close. The nose is small, The nose bridge is small. Eyes are slanted ("mongoloid eye slant”), there are small skinfolds on the inner corners of the eyes (epicanthus). Dots on the iris ("Brushfield spots"), degenerative signs on the retine and defective development on the edges (hypoplasia). The transparency of the lenses may be decreased. Refractive disorders – mainly myopia – nystagmus, astygmia, tear duct block (dacryostenosis), adulthood cataracts may occur. Teeth are frequently short, irregular teeth, but decay is less frequent. Parodontal issues often arise. Carpal bones and fingers are short. A so-called four-finger palmar crease is often seen. There is a visibly wide gap between big toes and the second toe. The pelvis is underdeveloped. The acetabular cup is shallow. Heart development disorders occur in about 40-60% of cases, which are mostly ventricular and atrial septum defects, open Botallo ducts, or less frequently valve problems, as well as issues with the arteria subclavia. The skin, especially on the neck and the back, are loose with lots of tissue present, dry and hyperkeratosis. The hair is thin and rare. Male patients often have relatively small penises and underdeveloped testicles. Women may occasionally conceive. Men are generally infertile. The central nervous system displays typically mental handicap of varying degrees.
The average IQ is between 25 and 50.
Muscle tone improves with time. Mental capabilities are usually better than would be expected based on IQ. Adults are as tall as healthy 15-year-olds. Eye-hand coordination is poor, but can be improved with proper training. Kids affected by Down syndrome are friendly, easy to manage, seek and are able to demonstrate love. They are sometimes surprisingly musical. Their life expectatncy is determined by the gravity of related, maily cardio-vascular conditions.
Compared to the healthy population, the life expectancy is as follows:
Down syndrome patients are more susceptible to infections, and a type of leuchemia is more frequent in their population. Their immune systems are weaker than the average.
As Down szndrome is caused multiple genetic disorders, it caanot be cured. Treatment is aimed at the management of associated medical conditions and mental development, as well as preparing the patient for independent life ("habilitation"), at which Hungary is recognized internationally.
By now, many Down syndrome patients can be developed to be capable of independent, balanced lifestyles. Children that used to be considered incapable of development (“idiots”) are capable of surprising performance as members of society. There are Down syndrome patients with drivers licenses in the US, and one of them is a popular character in a soap opera in Hungary.