Chromosomal Abnormality

Chromosomal abnormality

       Chromosomal abnormality, aberrations or anomalies are disruptions in the normal chromosomal content of a cell. Chromosomal aberrations are the changes in the structure of chromosomes. It has a great role in evolution.It also involve the gain, loss or rearrangement of visible amounts of genetic material.Some chromosomal conditions are caused by changes in the number of chromosomes. These changes are not inherited, but occur as random events during the formation of reproductive cells (eggs and sperm). An error in cell division called non-disjunction results in reproductive cells with an abnormal number of chromosomes. For example, a reproductive cell may accidentally gain or lose one copy of a chromosome. If one of these atypical reproductive cells contributes to the genetic makeup of a child, the child will have an extra or missing chromosome in each of the body’s cells.

Changes in chromosome structure can also cause chromosomal disorders. Some changes in chromosome structure can be inherited, while others occur as random accidents during the formation of reproductive cells or in early fetal development.
Some chromosome abnormalities do not cause disease in carriers, such as translocations, or chromosomal inversions, although they may lead to a higher chance of birthing a child with a chromosome disorder. Abnormal numbers of chromosomes or chromosome sets, aneuploidy, may be lethal or give rise to genetic disorders.

 Each of our chromosomes has a characteristic structure and displays a specific pattern of dark and light bands when stained with chemicals. These features are conserved in all human beings, making the different chromosomes easy to identify and distinguish from each other under a microscope. They define what is known as a normal karyotype - as a full set of chromosomes from an individual which can be compared to a "normal" karyotype for the species via genetic testing. Any deviation from the normal karyotype, in terms of chromosome number or structure, is known as a chromosome abnormality. A chromosome anomaly may be detected or confirmed in this manner.

            The gain or loss of DNA from chromosomes can lead to a variety of genetic disorders. Human examples include:

• Cri du chat, which is caused by the deletion of part of the short arm of chromosome 5. "Cri du chat" means "cry of the cat" in French, and the condition was so-named because affected babies make high-pitched cries that sound like those of a cat. Affected individuals have wide-set eyes, a small head and jaw, and are moderately to severely mentally retarded and very short.
• Wolf-Hirschhorn syndrome, which is caused by partial deletion of the short arm of chromosome 4. It is characterized by severe growth retardation and severe to profound mental retardation.
• Down syndrome, usually is caused by an extra copy of chromosome 21 (trisomy 21). Characteristics include decreased muscle tone, stockier build, asymmetrical skull, slanting eyes and mild to moderate mental retardation.
• Edwards syndrome, which is the second-most-common trisomy; Down syndrome is the most common. It is a trisomy of chromosome 18. Symptoms include mental and motor retardation and numerous congenital anomalies causing serious health problems. Ninety percent die in infancy; however, those that live past their first birthday usually are quite healthy thereafter. They have a characteristic clenched hands and overlapping fingers.
• Patau Syndrome, also called D-Syndrome or trisomy-13. Symptoms are somewhat similar to those of trisomy-18, but they do not have the characteristic hand shape.
• Idic15, abbreviation for Isodicentric 15 on chromosome 15; also called the following names due to various researches, but they all mean the same; IDIC(15), Inverted dupliction 15, extra Marker, Inv dup 15, partial tetrasomy 15
• Jacobsen syndrome, also called the terminal 11q deletion disorder. This is a very rare disorder. Those affected have normal intelligence or mild mental retardation, with poor expressive language skills. Most have a bleeding disorder called Paris-Trousseau syndrome.

Types of chromosomal abnormalties

There are many types of chromosome anomalies. They can be organized into two basic groups, numerical and structural abnormalties.

1)    Numerical  chromosomal  abnormality

This is called aneuploidy (an abnormal number of chromosomes), and occurs when an individual is missing either a chromosome from a pair (monosomy) or has more than two chromosomes of a pair (trisomy, tetrasomy, etc.). These type of birth defects occur when there is a different number of chromosomes in the cells of the body than is usually found. So, instead of the usual 46 chromosomes in each cell of the body, there may be 45 or 47 chromosomes. Having too many or too few chromosomes is a cause of some birth defects. Most human cells contain 23 pairs of chromosomes, for a a total of 46. When sex cells are produced, these pairs normally separate, which is called disjunction. A sex cell, or a gamete, thus has 23 chromosomes when this happens as it should. Sometimes, however, a pair will not separate — which is called nondisjunction — giving one gamete too many chromosomes and another too few. When these abnormal sex cells are involved in fertilization, the resulting cell will have the wrong number of chromosomes. If the cell has too many chromosomes, this is called polyploidy. Often, the cell only has one extra copy of a certain chromosome. If the cell has one copy of a chromosome, it is called a monosomic cell.

In humans an example of a condition caused by a numerical anomaly is Down Syndrome, also known as Trisomy 21 (an individual with Down Syndrome has three copies of chromosome 21, rather than two). Turner Syndrome is an example of a monosomy where the individual is born with only one sex chromosome, an X.

Trisomy

The term "trisomy" is used to describe the presence of three chromosomes, rather than the usual pair of chromosomes. For example, if a baby is born with three #21 chromosomes, rather than the usual pair, the baby would be said to have "trisomy 21." Trisomy 21 is also known as Down syndrome. Other examples of trisomy include trisomy 18 and trisomy 13. Again, trisomy 18 or trisomy 13 simply means there are three copies of the #18 chromosome (or of the #13 chromosome) present in each cell of the body, rather than the usual pair. The effects range from moderate to severe, and people who have Down syndrome have characteristic facial features, a short stature and heart defects. They often suffer from respiratory diseases, have a shorter life span and have some degree of mental retardation.

            Patau syndrome results from a trisomy of chromosome 13. It causes severe eye, brain and circulatory defects. Cleft palate is often a result, and these children rarely live longer than a few months. Children who have Edward’s syndrome also live for only a few months, in most cases. This is because all of their organs are affected in some way. Edward's syndrome is caused by trisomy 18. In people who have Klinefelter’s syndrome, the sex-determining chromosomes — normally XX for females and XY for males — are one Y chromosome and two X chromosomes. These individuals are male, but the presence of an extra X chromosome causes body proportions that are female and smaller testes, with no sperm production. Similar chromosome disorders result in XYY males or XXYY males, but their effects are much different and can vary widely in their nature and their degree.

 Monosomy

The term "monosomy" is used to describe the absence of one member of a pair of chromosomes. Therefore, there is a total of 45 chromosomes in each cell of the body, rather than 46. For example, if a baby is born with only one X sex chromosome, rather than the usual pair (either two X's or one X and one Y sex chromosome), the baby would be said to have "monosomy X." Monosomy X is also known as Turner syndrome.

 Children who have Turner’s syndrome have only one X chromosome and no Y chromosome, so they have only 45 chromosomes. This is the only monosomy that is not always lethal in humans, although it usually results in miscarriage. These babies who are born are female, but they are small in stature and do not mature sexually.

A few numerical abnormalities support development to term either because the chromosome has relatively few genes (13, 18, 21, Y-chromosome) or because there is a natural mechanism to adjust gene dosage even in normal people (X-chromosome). The most common numerical abnormalities are listed below

The major numerical abnormalities that survive to term

Syndrome	Abnormality	Incidence per 10 000 births	Lifespan (years)
Down	Trisomy 21	15	40
Edward's	Trisomy 18	3	<1
Patau's	Trisomy 13	2	<1
Turner’s	Monosomy X	2 (female births)	30-40
Klinefelter’s	XXY	10 (male births)	Normal
XXX	XXX	10 (female births)	Normal
XXY	XYY	10 (male births)	Normal

Nondisjunctions in human cells are relatively common. The results are often lethal to the fetus, so it usually doesn't survive. There are several of these types of chromosome disorders that do not prevent the baby from being born, however.

2)      Structural chromosomal abnormalty

Structural chromosome abnormalities occur when there is a change in the structure or components of a chromosome. The total number of chromosomes is usually normal (46 total per cell). Structural chromosome abnormalities occur when part of a chromosome is missing, a part of a chromosome is extra, or a part has switched places with another part. Ultimately, this leads to having too much or too little genetic material, which is a cause of some birth defects.Each chromosome has many segments which are usually divided into a "short arm" and a "long arm" of the chromosome. The short arm which is the upper half of the chromosome, is known as the "p arm" and the long arm, which is the lower half of the chromosome, is the "q arm." The centromere is the center part of a chromosome that appears "pinched" between the p and q arms

           Structural abnormalities can be unbalanced or balanced. The former are similar to numerical abnormalities in that genetic material is either gained or lost. The abnormalities range from the loss or duplication of whole chromosome arms to the deletion or duplication of tiny chromosome fragments barely visible under the microscope. However, even these tiny deviations (microdeletions and microduplications) can encompass several to many genes and have severe effects. Below is a list of some common deletion and microdeletion syndromes.

Unbalanced structural abnormalities (p = short arm, q = long arm)

Syndrome	Abnormality	Incidence
Wolf-Hirschhorn	Deletion, tip of 4p	1 in 50 000
Cri-du-chat	Deletion, tip of 5p	1 in 50 000
WAGR	Microdeletion, 11p
Prader-Willi/Angelman	Microdeletion, 15p
DiGeorge	Microdeletion, 22q

Balanced structural abnormalities involve the rearrangement of genetic material but no overall gain or loss. Examples include inversions (where a segment is removed from a chromosome, turned on its axis and sealed back in place), translocations (where part of one chromosome becomes attached to another) and ring chromosomes (where the ends of the long and short arms fuse together to form a circle).

Balanced abnormalities can have an immediate effect if a gene is disrupted by the breakpoint, if two genes are fused together, or if the relocation of a gene causes it to be expressed at a higher or lower level than usual. However, the major consequence is to prevent normal chromosome pairing at meiosis, leading to the production of sperm and eggs with incomplete or partially duplicated chromosome sets.

            Structural chromosomal abnormalties can take the following form

• Deletions: A portion of the chromosome is missing or deleted. Known disorders in humans include Wolf-Hirschhorn syndrome, which is caused by partial deletion of the short arm of chromosome 4; and Jacobsen syndrome, also called the terminal 11q deletion disorder.
• Duplications: A portion of the chromosome is duplicated, resulting in extra genetic material. Known human disorders include Charcot-Marie-Tooth disease type 1A which may be caused by duplication of the gene encoding peripheral myelin protein 22 (PMP22) on chromosome 17.
• Translocations: A portion of one chromosome is transferred to another chromosome. There are two main types of translocations:
• Reciprocal translocation: Segments from two different chromosomes have been exchanged.
• Robertsonian translocation: An entire chromosome has attached to another at the centromere - in humans these only occur with chromosomes 13, 14, 15, 21 and 22.
• Inversions: A portion of the chromosome has broken off, turned upside down and reattached, therefore the genetic material is inverted.
• Insertions: A portion of one chromosome has been deleted from its normal place and inserted into another chromosome.
• Rings: A portion of a chromosome has broken off and formed a circle or ring. This can happen with or without loss of genetic material.
• Isochromosome: Formed by the mirror image copy of a chromosome segment including the centromere

CAUSES, DIAGNOSIS, TREATMENT AND INHERITANCE

   Causes

Chromosomal abnormalities usually result from an error that occurs when an egg or sperm cell develops. It is not known why these errors occur. As far as we know, nothing that a parent does or doesn’t do before or during pregnancy can cause a chromosomal abnormality in his or her child.The question of what causes chromosomal abnormalities is a little more complex. The simplest answer is that "it just happens." Cell division is a complex process with a lot of things that can go wrong, so it follows that sometimes things do go wrong. A sperm or egg cell may end up with the wrong number of chromosomes or with chromosomes with missing or extra pieces, which ultimately go on to cause problems such as miscarriage or stillbirth (or lead to genetic disorders).The following factors have been implicated

1)      late pregnancy made the baby inside the mother have a higher risk of getting Down Syndrome

2)      Electromagnetic waves like UV light or X-ray cause our chromosome to mutate

3)      Family inheritance

4)      Non disjunction

  Diagnosis

Screening tests

Screening tests indicate whether an abnormality is likely, without risk to the foetus.

Serum screen

This is a blood test performed at 15 to 20 weeks. It measures the levels of pregnancy hormones in the mother's blood.

By combining these results with the mother's age, it is possible to calculate the risk of the baby having Down's syndrome.
The blood test is not a foolproof and, occasionally, a Down's baby will be born to a mother with a low-risk result.

Nuchal translucency measurement

Ultrasound is used to measure the fluid space at the back of the foetus' neck at 11 to 14 weeks. (Nucha, pronounced nooka, is the nape of the neck). Down's babies have a bigger space than unaffected pregnancies. By combining this measurement with your age and sometimes with hormone measurements in your blood, it is possible to calculate the risk of carrying an affected baby. If the risk is high, you may want to consider a diagnostic test.

        Chromosomal abnormalities can be diagnosed before birth using prenatal tests [amniocentesis or chorionic villus sampling (CVS)] or after birth using a blood test. Cells obtained from these tests are grown in the laboratory, and then their chromosomes are examined under a microscope. The lab makes a picture (karyotype) of all the person’s chromosomes, arranged in order from largest to smallest. The karyotype shows the number, size and shape of the chromosomes and helps experts identify any abnormalities.
Analysing cells from the foetus is the only way a chromosome abnormality can be diagnosed with certainty. A diagnostic test is performed when:

• a woman is considered at high risk because of the screening test.
• a woman is considered at high risk because she has previously had a pregnancy affected by a chromosomal or genetic disorder.
• an ultrasound examination has detected features or abnormalities indicating an increased risk of a chromosome abnormality.
• a woman requests it because she is concerned that her baby has a chromosome abnormality.

There are two types of diagnostic test: amniocentesis and chorionic villus sampling (CVS). Which test you are offered will depend on the hospital where you plan to give birth.

Amniocentesis

Amniocentesis analyses a sample of the fluid surrounding the foetus in the womb (the amniotic fluid). It is performed from 15 weeks of pregnancy onwards.

Using ultrasound to guide the way, a fine needle is inserted through the mother's abdomen and into the fluid surrounding the foetus. 20ml of amniotic fluid is removed and sent for analysis.

Chorionic villus sampling (CVS)

CVS analyses a sample of the placenta and is performed from 11 weeks onwards. Using ultrasound to guide the way, a needle is inserted through the mother's abdomen into the developing placenta. Suction is applied and a small sample of tissue is sent to the laboratory.

The procedure usually takes 5 to 10 minutes. It is a little more uncomfortable than amniocentesis for the mother. The foetus is unaware of the procedure.
With modern techniques, a preliminary result may be available within 48 hours. The final result will be ready in two weeks.

   Treatment
                There are are no treatment for chromosomal abnormalities.

   Inheritance
                Although it is possible to inherit some types of chromosomal abnormalities, most chromosomal disorders (such as Down syndrome and Turner syndrome) are not passed from one generation to the next.
Some chromosomal conditions are caused by changes in the number of chromosomes. These changes are not inherited, but occur as random events during the formation of reproductive cells (eggs and sperm). An error in cell division called nondisjunction results in reproductive cells with an abnormal number of chromosomes. For example, a reproductive cell may accidentally gain or lose one copy of a chromosome. If one of these atypical reproductive cells contributes to the genetic makeup of a child, the child will have an extra or missing chromosome in each of the body’s cells.
Changes in chromosome structure can also cause chromosomal disorders. Some changes in chromosome structure can be inherited, while others occur as random accidents during the formation of reproductive cells or in early fetal development. Because the inheritance of these changes can be complex, people concerned about this type of chromosomal abnormality may want to talk with a genetics professional.
Some cancer cells also have changes in the number or structure of their chromosomes. Because these changes occur in somatic cells (cells other than eggs and sperm), they cannot be passed from one generation to the next