General information on genetics
In each of our cells there exists a nucleus which contains the different chromosomes. These chromosomes are long chains consisting of hereditary material (DNA).
Chromosomes can be classified according to size and form, and numbered of large to small. These classified chromosomes form a karyotype. In each cell we have 2 copies of each chromosome, of which one originates from our father and one from our mother. So there are 23 chromosome pairs, and the total sum of chromosomes is 46. In the germline (egg from the woman and sperm from the man), however, there are 23 chromosomes, and only one copy of each chromosome pairs is present. When the 23 chromosomes from the egg meet with the 23 chromosomes from sperm cell, a fertilised egg or zygote with 46 chromosomes arises. From this zygote the child will develop. 44 of the 46 chromosomes (22 pairs) are present in both women and men : these chromosomes called autosomes. The remaining 2 chromosomes are called sex chromosomes. There are 2 sort of sex chromosomes : the X and the Y chromosome.
A woman has two X-chromosomes and no Y chromosome, because she gets an X chromosome from both her father and her mother. A man has two different sex chromosomes: an X chromosome that he inherits from his, and a Y chromosome which comes from its father. A man can make therefore both sperm cells warrants with an X chromosome, and an Y chromosome. A woman has only eggs with an X chromosome. If a sperm cell fertilising the egg (which always contain an X chromosome) contains an Y chromosome the resulting child will be a boy (XY). If a sperm cell contains an X chromosome, a girl (XX) will develop.
Because we have 2 copies of each autosome, we have 2 copies of each autosomal genes. Genes which lie on the X chromosome have 1 copy in a man and 2 in a woman. Genes on the Y chromosome are present in 1 copy in men, whereas women do not have these genes.
Our hereditary material is made of a chemical substance called Deoxy Nucleic Acid (abbreviated: DNA).
This DNA actually is a long chain of four different nucleotides: adenine (A), cytosine (C), guanine (G) and thymine (T). The DNA chain is very long and contains approximately 3 billion of these nucleotides. The DNA chain is made out of 46 different DNA chains, which are called chromosomes. These chromosomes harbour all the different genes, which is a separate unit of DNA with a specific function. Humans has approximately 25,000 genes. Most of these genes are responsible for the production of a specific protein. Changes in DNA are called mutations. These mutations can be the cause of hereditary diseases.
The chromosomes exist from separate units of DNA called genes, which all have their own function. We have approximately 25,000 genes in each cell. Most of these genes have been discovered during the Human Genome Project, a very important scientific project in which research workers from the all over the world took part in order to decipher the DNA code. A large part of this project has already been completed, and most of our genes have been identified. Geneticists are now trying to elucidate the function of all these genes. Most genes encode one or more specific proteins, and each of these proteins has its own function in cell. These proteins determine all our characteristics, such as how we look (the colour of our eyes, etc), but also all genetic diseases.
Down syndrome or trisomy 21
The most well-known example of a chromosome anomaly is Down syndrome. In 1866 Doctor Langdon Down described this chromosome anomaly for the first time in the medical literature. In genetics, and in medicine in general, it is quite common to call diseases after the doctor that described them for the first time.
A syndrome is a disease with anomalies of several organs, such as the eyes, brain and the heart. Many syndromes are due to a genetic anomaly.
Down syndrome is caused by an extra (third) chromosome 21. These individuals have therefore not 46, but 47 chromosomes. Whereas everyone has two chromosomes 21, they have 3. Therefore, Down syndrome is also called trisomy 21. The trisomy is usually due to an abnormality of the egg of the mother: normally all reproductive cells (eggs and sperms) carry only 23 chromosomes (one of each). At fertilisation the 23 chromosomes from the female egg than join the 23 chromosomes from the male sperm to form a fertilised egg or zygote with the normal 46 chromosomes. When one of the reproductive cells has an extra chromosome 21, the fertilised egg has 47 chromosomes with 3 chromosomes 21, resulting in Down syndrome.
With the age of the mother, particularly from 36 year on, increases the risk that the egg contains 2 instead of 1 chromosome 21. Therefore, also the risk on a child with Down syndrome steadily increases with maternal age. For this reason pregnant woman with a certain age (frequently from the age of 36 years) have prenatal tests to exclude Down syndrome. An average couple has risk of approximately 1 on 200 on a child with a chromosome anomaly, and 1 on 600 for trisomy 21.
Edwards syndrome or trisomy 18
Also trisomy 18 or Edwards syndrome is a serious syndrome where the babies generally die in the first life year. The babies have malformations of many organs.
Patau syndrome or trisomy 13
Trisomy 13 is a very severe chromosome anomaly with early death. Trisomy 13 babies frequently have cleft lip and palate, and congenital heart malformations.
Turner syndrome or monosomy X
Girls with Turner syndrome have 1 instead of 2 X chromosomes (monosomy X). They are small, have no menstruation and are infertile. Frequently also there exists a broad neck (webbed neck). The intellectual development is normal or slightly behind.
Klinefelter syndrome is caused by an extra copy of the X chromosome (XXY). It only affects boys. that may have speech delays and other learning disabilities and tend to be taller than average, but otherwise have few physical anomalies. Men with Klinefelter syndrome are usually infertile and often benefit from hormone treatment starting at puberty.
Ultrasound uses ultrasonic waves to make a picture of the fetus. The echo apparatus sends out sound waves to the body of mother and child, and catches the echos (hence the denomination echography) of these sound waves. These echos are then converted into a picture of the fetus. Ultrasound is very frequently used in medicine to visualise internal structures, just like CT scan and MRI. The ultrasonic sound waves are harmless for mother and fetus.
With ultrasound it is possible to visualise structural anomalies of the fetus such as growth retardation, neural tube defects (spina bifida), hydrocephalus, heart malformations, etc. Because ultrasound only visualises the form and not the function, ultrasound cannot exclude functional defects (eg mental retardation, epilepsy, etc). A fetal ultrasound to visualise the fetus and its organs is called a structural fetal ultrasound; it is best performed around week 18-19 of gestation. Ultrasound is the most important prenatal screening test, and should therefore be performed in each pregnancy, certainly when there is an increased risk for a child with a congenital or genetic anomaly. This is the case if there is (was) a previous child with such anomaly, or if of the parents themselves have such an anomaly. Some malformations can be visualised already very early in pregnancy (from week 12 on).
With an amniocentesis approximately 10-20 ml amniotic fluid is absorbed with a needle introduced into the amniotic cavity through the abdomen. Amniocentesis causes little discomfort or pain for mother and foetus (to compare with an injection of medicines). The procedure has only a small risk for the pregnancy. In approximately 1 on 200 cases (0,5%) miscarriage results because of haemorrhage, infection or leaking of amniotic fluid after the puncture. Of course, not every miscarriage after an amniocentesis is the consequence of this test, because also women without amniocentesis can have a miscarriage. The risk of touching the fetus with the needle is very small.
An amniocentesis is performed to obtain amniotic fluid and foetal cells that float in the amniotic fluid. These cells are fetal cells from the skin and internal membranes of the fetus. Both amniotic fluid and amniotic cells can be used for prenatal testing.
Tests that can be performed are cytogenetic a