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chromosomal rearrangments
A chromosomal rearrangement means that pieces of chromosomes are missing, duplicated (there are extra copies), or moved around.
The effects vary. They depend on which chromosome pieces are involved and how they are rearranged. Some have no effect, some are incompatible with life, and others are somewhere between.
How do people get chromosomal rearrangements
Most of the time, chromosomal rearrangements happen during egg and sperm formation. During the recombination step, pairs of chromosomes break and swap pieces. If the chromosomes line up unevenly or if the breaks are not repaired properly, pieces of chromosomes may be rearranged. The chromosomes are then distributed into egg or sperm cell. If the cell participates in fertilization, the embryo ends up with extra, missing, or rearranged chromosome pieces. As the embryo grows and the cells divide, the chromosome arrangement is copied into every cell in the baby's body.
Sometimes, chromosome rearrangements happen soon after fertilization. The rearrangement is then copied to all or some of the baby's cells.
How are chromosomal rearrangements diagnosed?
Chromosomal rearrangements are diagnosed through genetic testing. Most tests use DNA from a blood sample or a cheek swab.
Some rearrangements happen more often than others, and some give rise to syndromes with signature characteristics. Based on a person's characteristics, a doctor may order a specific test on just one chromosome to a confirm a diagnosis. Other tests look more broadly at all of the chromosomes.
Some rearrangements can be detected before birth, through prenatal genetic testing. These tests are done during pregnancy on a DNA sample from the developing baby. They measure the number and arrangement of all of the baby's chromosomes.
Balanced rearrangements
Rearrangements fall broadly into two categories: balanced and unbalanced.
A person with a balanced chromosomal rearrangement has a complete set of genetic information. However, some chromosome pieces have been moved around.
Most of the time, people who have a balanced chromosomal rearrangement are perfectly healthy. But some balanced rearrangements have an effect. For example, if a chromosome break falls in the middle of a gene, the function of that gene may be disrupted.
Many people with balanced rearrangements are unaware of their condition until they try to have children. The biggest issue they face is that they are likely to passing an unbalanced rearrangement to their children. They may have trouble conceiving, they may have a child with a genetic disorder, or they may experience multiple pregnancy losses. The effects depend on the chromosome regions involved. Any of these situations would prompt genetic testing of the parents, which would reveal the translocation.
Balanced rearrangements are fairly common, affecting about 1 in 1,000 people. They make up a large proportion of couples seeking fertility treatment.
Unbalanced Rearrangements
In an unbalanced rearrangement, pieces of chromosomes are either missing or duplicated. Missing information is called a deletion, and duplicated information is called an insertion. Some unbalanced rearrangements also involve translocation: where a piece of a chromosome is broken off and reattached to a different chromosome.
Most unbalanced rearrangements have an effect. But the effects vary greatly, depending on which genes are on the chromosome pieces that are missing or duplicated.
Unbalanced rearrangements are common in the children of parents who carry a balanced rearrangement. But they can also happen in the children of parents who are genetically normal. If a genetically normal couple has one child with a chromosomal rearrangement, they are unlikely to have a second child with the same condition.
EXAMPLES OF UNBALANCED CHROMOSOMAL REARRANGEMENTS
What is Cri-du-Chat Syndrome?
Cri-du-chat is French for "cry of the cat," referring to the distinctive cry of children with this condition. The cry is caused by the way the larynx (voice box) develops, one of the features associated with this disorder. It usually becomes less noticeable as the baby gets older, making it harder for doctors to identify Cri-du-chat after age two.
People with Cri-du-chat syndrome have a deletion in one of their copies of chromosome 5. The size of the deletion can vary.
The features of Cri-du-chat syndrome can vary. They depend in part on how much of chromosome 5 is deleted. Babies with Cri-du-chat are usually small at birth, and they may have problems with their lungs. Often, the larynx doesn't form correctly, which causes the signature cat-like cry.
People who have Cri-du-chat tend to have distinctive facial features. They may have a small head (microcephaly), a round face, a small chin, widely set eyes, folds of skin over their eyes, and a small bridge of the nose.
There can be effects inside the body, as well. Children can have problems with their heart, muscles, bones, hearing, or vision. Most have low muscle tone. As they grow, people with Cri-du-chat usually have difficulty walking and talking. They may have behavior issues, such as hyperactivity or aggression. Most have severe intellectual disability. If there are no major medical problems, life expectancy is about average.
One of the commonly deleted genes in people with this syndrome is TERT (telomerase reverse transcriptase). This gene codes for a protein that helps to keep the tips of chromosomes (telomeres) intact. Other key genes are important for the formation of the throat, larynx, face, and brain.
Interesting facts about cri-du-chat syndrome
The geneticist Jerome Lejeune identified Cri-du-chat syndrome in 1963. He also discovered the genetic basis of Down syndrome.
Cri-du-chat is one of the most common syndromes caused by a chromosomal deletion. It affects between 1 in 20,000 and 1 in 50,000 babies.
In 80 percent of cases, the chromosome carrying the deletion comes from the father's sperm rather than the mother's egg.
If neither parent carries a balanced translocation, it is highly unlikely that they will have a second child with this or any chromosomal deletion.
Diagnosing Williams Syndrome
The deletion in Williams syndrome too small to be seen with a microscope (fewer than 5 million bases of DNA are missing). The small size of the deletion makes Williams syndrome a little trickier to diagnose than other deletion syndromes.
If a person's characteristics strongly suggest Williams syndrome, a doctor may order a test that uses a method called FISH (fluorescent in situ hybridization). If a doctor is less certain about the diagnosis, they may order a test that looks at other chromosomes in addition to chromosome 7. These tests usually use DNA sequencing or microarray analysis.
It is technically possible to diagnose Williams syndrome before birth. But not all prenatal genetic tests look for the specific deletion that causes it.
Interesting Facts About Williams Syndrome
One out of every 10,000 babies is born with Williams syndrome.
If they are genetically normal, the parents of a child with Williams syndrome are unlikely to have a second child with the syndrome.
If someone with Williams syndrome has a child, there is a 50 percent chance the child will also have the syndrome. But most people with Williams syndrome do not have children.
Some cases of Down syndrome arise in the children of parents who carry a Robertsonian translocation that involves chromosome 21. Down syndrome can also be caused by having some duplicated information from chromosome 21, either as an insertion within chromosome 21 or a translocation involving a piece of chromosome 21. Usually the effects of a partial duplication are milder than those of having an entire extra copy of chromosome 21.
Some cases of Turner syndrome are caused by a deletion of a piece of the X chromosome. In these individuals, the effects are usually milder than if they were missing their entire X chromosome.