Chromosomal Abnormalities

In these disorders, entire chromosomes, or large segments of them, are missing, duplicated, or otherwise altered.

Cri-du-Chat Syndrome

What is Cri-du-Chat syndrome?

The name of this syndrome is French for "cry of the cat," referring to the distinctive cry of children with this disorder. The cry is caused by abnormal larynx development, one of the many symptoms associated with this disorder. It usually becomes less noticeable as the baby gets older, making it difficult for doctors to diagnose cri-du-chat after age two. Cri-du-chat is caused by a deletion (the length of which may vary) on the short arm of chromosome 5. Multiple genes are missing as a result of this deletion, and each may contribute to the symptoms of the disorder. One of the deleted genes is TERT (telomerase reverse transcriptase). This gene is important during cell division because it helps to keep the tips of chromosomes (telomeres) in tact.

Cri-du-Chat Karyotype

How do people get Cri-du-Chat syndrome?

A deletion is caused by a break in the DNA molecule that makes up a chromosome. In most cases, the chromosome break occurs while the sperm or egg cell (the male or female gamete) is developing. When this gamete is fertilized, the child will develop cri-du-chat syndrome. The parent, however, does not have the break in any other cells of the body and does not have the syndrome. In fact, breaks are so rare that it is very unlikely to happen again if the parent has another child.

It is possible for a child to inherit a broken chromosome from a parent who also has the disorder.

cri-du-chat

What are the symptoms of Cri-du-Chat syndrome?

Cri-du-Chat Person

Babies with cri-du-chat are usually small at birth, and they may have respiratory problems. Often, the larynx doesn't develop correctly, which causes the signature cat-like cry.

People who have cri-du-chat have very distinctive features. They may have a small head (microcephaly), an unusually round face, a small chin, widely set eyes, folds of skin over their eyes, and a small bridge of the nose.

Several problems occur inside the body, as well. A small number of children have heart defects, muscular or skeletal problems, hearing or sight problems, or poor muscle tone. As they grow, people with cri-du-chat usually have difficulty walking and talking. They may have behavior problems (such as hyperactivity or aggression) and severe intellectual disability. If no major organ defects or other critical medical conditions exist, life expectancy is normal.

How do doctors diagnose cri-du-chat syndrome?

Doctors most often identify cri-du-chat by the infant's cat-like cry. Other signs are microcephaly, poor muscle tone, and mental retardation.

It is also possible to test for cri-du-chat (and other chromosomal abnormalitites) before the baby is born. Testing can be done either (1) on a tiny sample of tissue from outside the sac where the baby develops (chorionic villus sampling (CVS)), or (2) on a sample of the amniotic fluid that surrounds the baby (amniocentesis).

How is cri-du-chat syndrome treated?

Although there is no real treatment for cri-du-chat syndrome, children with the disorder can go through therapy to improve their language skills, motor skills, and to help them develop as normally as possible.

Interesting facts about cri-du-chat syndrome

The geneticist Jerome Lejeune identified cri-du-chat syndrome in 1963. He also discovered the genetic abnormality that causes 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 the cases, the chromosome carrying the deletion comes from the father's sperm rather than the mother's egg.

Deletions during the formation of an egg or sperm, are caused by unequal recombination during meiosis. Recombination normally occurs between pairs of chromosomes while they are lined up at the metaphase plate. If the pairs of chromosomes don't line up correctly, or if the chromosome breaks aren't repaired properly, the chromosomes can gain or lose pieces. Unequal recombination at a certain location on chromosome 5 causes cri-du-chat syndrome.

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Down Syndrome

What is Down syndrome?

Down syndrome is a developmental disorder caused by an extra copy of chromosome 21 (which is why the disorder is also called "trisomy 21"). Having an extra copy of this chromosome means that individuals have three copies of each of its genes instead of two, making it difficult for cells to properly control how much protein is made. Producing too much or too little protein can have serious consequences. Genes on chromosome 21 that specifically contribute to the various symptoms of Down syndrome are now being identified.

How do people get Down syndrome?

Down syndrome is typically caused by what is called nondisjunction. Nondisjunction happens when a pair of chromosomes fails to separate during egg (or sperm) formation. When that egg unites with a normal sperm to form an embryo, the embryo ends up with three copies of chromosome 21 instead of the normal two. The extra chromosome is then copied in every cell as the baby develops.

Interestingly, nondisjunction events seem to occur more frequently in older women. This may explain why the risk of having a baby with Down syndrome is greater among mothers age 35 and older.

In rare cases, Down syndrome is caused by a Robertsonian translocation, which occurs when the long arm of chromosome 21 breaks off and attaches to another chromosome at the centromere. Carriers of such a translocation will not have Down syndrome themselves, but they can have children with Down syndrome.

To learn more about nondisjunction, translocation, and karyotypes, visit Using Karyotypes to Diagnose Genetic Disorders.
Trisomy 21 Karyotype


Nondisjunction

Nondisjunction happens when chromosomes are distributed incorrectly during egg or sperm formation. The gametes above either are missing or have an extra chromosome 21.

What are the symptoms of Down syndrome?

Kids

People with Down syndrome have distinct facial features: a flat face, a small broad nose, abnormally shaped ears, a large tongue, and upward-slanting eyes with small folds of skin in the corners.

People with Down syndrome have an increased risk of developing a number of medically significant problems, including respiratory infections, gastrointestinal tract obstruction (blocked digestive tract), leukemia, heart defects, hearing loss, hypothyroidism, and eye abnormalities. They also have moderate to severe intellectual disability; children with Down syndrome usually develop more slowly than their peers and have trouble learning to walk, talk, and take care of themselves.

Because of these medical problems, most people with Down syndrome have a decreased life expectancy. About half live to be 50 years of age.

How do doctors diagnose Down syndrome?

Two types of tests check for Down syndrome during pregnancy: screening and diagnostic tests.

Screening tests identify a mother who is likely carrying a baby with Down syndrome. The most common screening tests are the Triple Screen and the Alpha-Fetoprotein Plus. These tests measure levels of certain substances in the mother's blood.

Alternatively, ultrasounds (which use sound waves to look at the developing baby) allow the doctor to examine the fetus in the womb for the physical signs of Down syndrome.

To confirm a positive screening result, one of the following diagnostic tests can be performed: chorionic villus sampling (CVS), amniocentesis, and percutaneous umbilical blood sampling (PUBS). Each takes a sample from the placenta, amniotic fluid, or umbilical cord, respectively, to examine the baby's chromosomes and determine if he or she has an extra chromosome 21.

If Down syndrome is not diagnosed in the womb, doctors can usually recognize it after the baby is born by the distinctive facial features. The diagnosis is confirmed with a karyotype— picture of the baby's chromosomes.

Trisomy 21

How is Down syndrome treated?

There is no cure for Down syndrome. But physical therapy and/or speech therapy can help people with the disorder develop more normally. Screening for common medical problems associated with the disorder, followed by corrective surgery, can often improve quality of life. Moreover, enriched environments significantly increase children's capacity to learn and lead meaningful lives.

Interesting facts about Down syndrome

Down syndrome is really the only trisomy compatible with life. Only two other trisomies have been observed in babies born alive (trisomies 13 and 18), but babies born with these trisomies have only a 5% chance of surviving longer than one year.

In 90% of Trisomy 21 cases, the additional chromosome comes from the mother's egg rather than the father's sperm.

Down syndrome is the most common genetic disorder caused by a chromosomal abnormality. It affects 1 out of every 800 to 1,000 babies.

Down syndrome was originally described in 1866 by John Langdon Down. It wasn't until 1959 that French doctor Jerome Lejeune discovered it was caused by the inheritance of an extra chromosome 21.

47, XXY (Klinefelter syndrome)

[Note: Much of the medical literature defines Klinefelter syndrome as a person with an XXY chromosomal arrangement, and considers every XXY individual to have Klinefelter syndrome. However, many (including some XXY individuals themselves) consider Klinefelter syndrome to be a set of physical characteristics that are present in just some XXY individuals. While we do not promote one definite over the other, we wish to point out that the distinction is important to some people.]

What is 47, XXY (Klinefelter syndrome)?

47, XXY (or XXY) is a genetic condition caused when someone has two X chromosomes and one Y chromosome. Males normally have an X chromosome and a Y chromosome (46, XY), and females normally have two X chromosomes (46, XX).

Because people with an XXY chromosome arrangement have a Y chromosome, they are considered genetic males. Most XXY individuals develop as males, often not knowing they have an extra chromosome. Some will develop the varied and often subtle characteristics associated with Klinefelter syndrome. And a small proportion will develop as intersex (between male and female) or female. Physical characteristics may appear around the time of puberty, when gender identity and sexual characteristics begin to take shape.

Similar conditions are caused by additional X chromosomes (48, XXXY; 49, XXXXY), but they are much more rare. The more X chromosomes a person has, the stronger the physical characteristics and health problems tend to be, including intellectual disability.

Klinefelter Karyotype

How do people get 47, XXY (Klinefelter syndrome)?

XXY is usually caused by what is called nondisjunction. Nondisjunction happens when a pair of sex chromosomes fails to separate during egg (or sperm) formation. When an egg (or sperm) with an extra X chromosomes joins with a normal sperm (or egg), the resulting embryo will end up with three sex chromosomes (XXY) instead of the normal two (XX or XY). As the baby develops, the extra chromosome is then copied in every cell.

Nondisjunction leading to XXY is equally likely to happen in the mother's egg and the father's sperm. In about 10% of cases, chromosomes fail to separate when a cell divides very early in embryonic development, and only some of the baby's cells have an extra X chromosome. Such "mosaic" cases are usually mild and often remain undetected.

What are the symptoms of 47, XXY (Klinefelter syndrome)?

The XXY chromosome arrangement affects primarily sexual development. Typically, testes don't fully develop, and the levels of the hormone testosterone (important for male sexual development) are lower than average. As adults, nearly all XXY males are unable to make sperm and so cannot have biological children. Many men discover their condition only after they seek medical help for infertility.

The symptoms of XXY (Klinefelter syndrome) can be very subtle and are highly varied. Children and adults may be taller than average, with proportionally longer arms and legs, and they may have less-muscular bodies, more belly fat, wider hips, narrower shoulders, or minor to moderate learning disabilities. Changes that appear at puberty can include low growth of facial and body hair, development of breast tissue, and small testes.

XXY individuals are also more likely to develop certain medical conditions, including osteoporosis (weak bones), varicose veins, type 2 diabetes, and heart valve defects. As adults, they are just as likely as XX females to develop breast cancer and certain autoimmune disorders.

XXY Kids

How do doctors diagnose 47, XXY (Klinefelter syndrome)?

If a doctor suspects that an individual may be XXY (based on physical characteristics, most commonly infertility), the diagnosis can be made using a karyotype. A karyotype is an analysis of a patient's chromosomes taken from a blood sample.

XXY may also be diagnosed during a woman's pregnancy. Doctors can look for chromosome abnormalities in cells taken from the amniotic fluid surrounding the fetus (amniocentesis) or from the placenta (chorionic villus sampling, or CVS). About 10% of cases are diagnosed this way.

As many as 75% of XXY individuals are never diagnosed.

Learn more about nondisjunction and karyotypes on Using Karyotypes to Diagnose Genetic Disorders.

How is 47, XXY (Klinefelter syndrome) treated?

Knowing an individual's chromosomal status is important for both their physical and emotional health. Early diagnosis can alert doctors to the need for bone-density and hormone-level monitoring. Educators can be on the lookout for learning disabilities. XXY individuals also may need emotional support and counseling, especially during puberty. Boys who develop breast tissue or who do not develop facial or body hair may feel self-conscious. Teens may need support as they face gender identity issues.

Teens and adults who wish to be treated can be given hormones. The hormone testosterone will help them develop more typically male characteristics, and estrogen will help them develop more typically female characteristics. Those who choose can have surgery to remove breast tissue.

Many 47, XXY individuals are quite typical males who receive no treatment. Those who wish to have children can often be helped with reproductive technologies.

Interesting facts about 47, XXY (Klinefelter syndrome)

XXY is one of the most common genetic conditions, affecting about 1 in 660 genetic males.

Klinefelter syndrome is named for Dr. Harry Klinefelter, who first reported its symptoms in 1942.

Turner Syndrome

What is Turner syndrome?

Turner syndrome is caused by a missing or incomplete X chromosome. People who have Turner syndrome develop as females. Some of the genes on the X chromosome are involved in growth and sexual development, which is why girls with the disorder are shorter than normal and have incompletely developed sexual characteristics.

To learn more about nondisjunction, visit Using Karyotypes to Diagnose Genetic Disorders
Turner Karyotype

How do people get Turner syndrome?

Normally, a girl inherits one X chromosome from her mother and one X chromosome from her father. But girls who have Turner syndrome are missing one of their X chromosomes.

Turner syndrome is typically caused by what is called nondisjunction. Nondisjunction happens when a pair of sex chromosomes fails to separate during the formation of a sperm (or egg). When sperm with no X chromosome unites with a normal egg to form an embryo, that embryo will have just one X chromosome (X rather than XX). As the embryo grows and the cells divide, the X chromosome will be missing from every cell of the baby's body.

The abnormality is not inherited from an affected parent (not passed down from parent to child), because women with Turner syndrome are usually sterile and cannot have children.

In about 20 percent of Turner syndrome cases, both X chromosomes are present, but one is abnormal. It may be shaped like a ring or missing some genetic material.

About 30 percent of girls with the disorder are missing the X chromosome in just some of their cells. This mixed chromosome pattern is known as mosaicism. Girls with this pattern may have fewer symptoms because they still have some normal (XX) cells.

One of the missing genes on the X chromosome is the SHOX gene, which is responsible for long bone growth. The missing SHOX gene is the reason girls who have the disorder are unusually short. Other missing genes regulate ovarian development, which influences sexual characteristics.

Nondisjunction

Nondisjunction happens when chromosomes are distributed incorrectly during egg and sperm formation. The gametes above either are missing or have an extra X chromosome.

What are the symptoms of Turner syndrome?

Turner syndrome affects growth and sexual development. Girls with this disorder are shorter than normal and may not start puberty when they should. This is because the ovaries (which produce eggs, as well as the sex hormones estrogen and progesterone) don't develop properly.

Turner syndrome usually does not affect intelligence. Common physical symptoms of Turner Syndrome include a stocky build, arms that turn out slightly at the elbow, a receding lower jaw, a short webbed neck, and a low hairline at the back of the neck.

Medical symptoms can include lymphedema (swelling of hands and feet), heart and/or kidney defects, high blood pressure, and infertility (inability to have children).

Turner Syndrome

How do doctors diagnose Turner syndrome?

About half of the cases are diagnosed within the first few months of a girl's life by the characteristic symptoms (swelling of the hands and feet, heart defect). Other patients are diagnosed in adolescence because they do not grow normally or go through puberty.

When a doctor suspects Turner syndrome, a blood sample can be used to make a karyotype (a chromosome analysis), and the diagnosis can be confirmed.

Turner syndrome may be diagnosed during pregnancy with chorionic villus sampling (CVS) or amniocentesis. Alternatively, an ultrasound (a machine that uses sound waves to look inside a mother's uterus) can identify the disorder by its physical symptoms before the baby is born.

How is Turner syndrome treated?

Hormone replacement therapy is the best way to treat this disorder. Teenagers are treated with growth hormone to help them reach a normal height. They may also be given low doses of androgens (male hormones that females also produce in small quantities) to increase height and encourage hair and muscle growth. Some patients may take the female hormone estrogen to promote sexual development.

Interesting facts about Turner syndrome

Turner Syndrome affects 60,000 females in the United States. This disorder is seen in 1 of every 2000 to 2500 baby girls, with about 800 new cases diagnosed each year.

In 75-80% of cases, the single X chromosome comes from the mother's egg; the father's sperm that fertilizes the egg is missing its sex chromosome.

Turner syndrome is named for Dr. Henry Turner, who in 1938 published a report describing the disorder.

The average height of an untreated woman with Turner syndrome is 4 feet 8 inches.

A female fetus (normally XX) that is missing one of its X chromosomes can survive, but a male fetus (normally XY) cannot. The X chromosome is a long DNA molecule with many genes that are needed for cells to function; it is essential for life. In contrast, the Y chromosome carries few genes and is not essential for life.

Williams Syndrome

What is Williams syndrome?

Williams syndrome is a rare genetic disorder that affects a child's growth, physical appearance, and cognitive development. People who have Williams syndrome are missing genetic material from chromosome 7, including the gene elastin. This gene's protein product gives blood vessels the stretchiness and strength required to withstand a lifetime of use. The elastin protein is made only during embryonic development and childhood, when blood vessels are formed. Because they lack the elastin protein, people with Williams Syndrome have disorders of the circulatory system and heart.

chr7-elastin

How do people get Williams syndrome?

A deletion is caused by a break in the DNA molecule that makes up a chromosome. In most cases, the chromosome break occurs while the sperm or egg cell (the male or female gamete) is developing. When this gamete is fertilized, the child will develop Williams syndrome. The parent, however, does not have the break in any other cells and does not have the syndrome. In fact, the break is usually such a rare event that it is very unlikely to happen again if the parent has another child.

It is possible for a child to inherit a broken chromosome from a parent who has the disorder. But this is rare because most people with Williams syndrome do not have children.

What are the symptoms of Williams syndrome?

The most common symptoms of Williams syndrome are intellectual disability, heart defects, and unusual facial features (small upturned nose, wide mouth, full lips, small chin, widely spaced teeth).

Other symptoms include low birth weight, failure to gain weight appropriately, kidney abnormalities, and low muscle tone.

People with this syndrome also exhibit characteristic behaviors, such as hypersensitivity to loud noises and an outgoing personality.

Williams Syndrome

How do doctors diagnose Williams syndrome?

Doctors can identify the syndrome by its distinctive physical characteristics. They can confirm the diagnosis by using a special technique called FISH (fluorescent in situ hybridization).

The chromosomal deletion that causes Williams Syndrome is so small that it cannot be seen in a karyotype. The deletion can be observed, however, with FISH. This technique allows DNA sequences to be labeled with a fluorescent chemical (called a probe) that lights up when exposed to ultraviolet (UV) light. The Williams Syndrome deletion can be detected by labeling the elastin gene with a fluorescent probe. The gene will light up under a UV light only if it is present; a lack of signal indicates a deletion.

How is Williams syndrome treated?

There is no cure for Williams syndrome. Patients must be continually monitored and treated for symptoms throughout their lives.

Williams FISH

Interesting facts about Williams syndrome

One out of every 10,000 babies is born with Williams syndrome.

Williams syndrome is considered a microdeletion syndrome, because the deletion is too small to be seen with a microscope (fewer than 5 million bases of DNA are deleted).

Deletions that happen during egg and sperm formation are caused by unequal recombination. Recombination normally occurs between pairs of chromosomes during meiosis. If the pairs of chromosomes don't line up correctly, or if the chromosome breaks aren't repaired properly, the structure of the chromosome can be altered. Unequal recombination occurs more often than usual at this location on chromosome 7, likely due to some highly repetitive DNA sequence that flanks the commonly deleted region.

  • Funding

    Funding provided by grant 51006109 from the Howard Hughes Medical Institute, Precollege Science Education Initiative for Biomedical Research.


APA format:

Genetic Science Learning Center. (2014, February 15) Chromosomal Abnormalities. Retrieved December 14, 2017, from http://learn.genetics.utah.edu/content/disorders/chromosomal/

CSE format:

Chromosomal Abnormalities [Internet]. Salt Lake City (UT): Genetic Science Learning Center; 2014 [cited 2017 Dec 14] Available from http://learn.genetics.utah.edu/content/disorders/chromosomal/

Chicago format:

Genetic Science Learning Center. "Chromosomal Abnormalities." Learn.Genetics. February 15, 2014. Accessed December 14, 2017. http://learn.genetics.utah.edu/content/disorders/chromosomal/.