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Genetics: Understanding Chromosome Disorders

Chromosomal abnormalities, in the form of aneuploidy, are very common among humans. Roughly 8 percent of all conceptions are aneuploid, and it's estimated that up to half of all miscarriages are due to some form of chromosome disorder. Sex chromosome disorders are the most commonly observed type of aneuploidy in humans, because X-chromosome inactivation allows individuals with more than two X chromosomes to compensate for the extra "doses" and survive the condition.

Four common categories of aneuploidy crop up in humans:

  • Nullisomy: Occurs when a chromosome is missing altogether. Generally, embryos that are nullisomic don't survive to be born.

  • Monosomy: Occurs when one chromosome lacks its homolog.

  • Trisomy: Occurs when one extra copy of a chromosome is present.

  • Tetrasomy: Occurs when four total copies of a chromosome are present. Tetrasomy is extremely rare.

Most chromosome conditions are referred to by category of aneuploidy followed by the number of the affected chromosome. For example, trisomy 13 means that three copies of chromosome 13 are present.

When chromosomes are left out

Monosomy (when one chromosome lacks its homolog) in humans is very rare. The majority of embryos with monosomies don't survive to be born. For liveborn infants, the only autosomal monosomy reported in humans is monosomy 21. Signs and symptoms of monosomy 21 are similar to those of Down syndrome. Infants with monosomy 21 often have numerous birth defects and rarely survive for longer than a few days or weeks. The other monosomy commonly seen in children is monosomy of the X chromosome. Children with this condition are always female and usually lead normal lives. Both monosomy 21 and monosomy 13 are the result of nondisjunction during meiosis.

Many monosomies are partial losses of chromosomes, meaning that part (or all) of the missing chromosome is attached to another chromosome. Movements of parts of chromosomes to other, nonhomologous chromosomes are the result of translocations.

Finally, monosomies can occur in cells as a result of mistakes that occur during cell division (mitosis). Many of these monosomies are associated with chemical exposure and various sorts of cancers.

When too many chromosomes are left in

Trisomies (when one extra copy of a chromosome is present) are the most common sorts of chromosomal abnormalities observed in humans. The most common trisomy is Down syndrome, or trisomy 21. Other less common trisomies include trisomy 18 (Edward syndrome), trisomy 13 (Patau syndrome), and trisomy 8. All these trisomies are usually the result of nondisjunction during meiosis.

Down syndrome

Trisomy of chromosome 21, commonly called Down syndrome, affects between 1 in 600 to 1 in 800 infants. People with Down syndrome have some rather stereotyped physical characteristics, including distinct facial features, altered body shape, and short stature. Individuals with Down syndrome are usually mentally delayed and often have heart defects. Nevertheless, they often lead fulfilling and active lives well into adulthood.

One of the most striking features of Down syndrome (and trisomies, in general) is the precipitous increase in the number of Down syndrome babies born to mothers over 35 years of age. Women between the ages of 18 and 25 have a very low risk of having a baby with trisomy 21 (roughly 1 in 2,000). The risk increases slightly but steadily for women between the ages of 25 and 35 (about 1 in 900 for women 30 years old) and then jumps dramatically. By the time a woman is 40 years old, the probability of having a child with Down syndrome is one in 100. By the age of 50, the probability of conceiving a Down syndrome child is 1 in 12. Why does the risk of Down syndrome increase in the children of older women?

The majority of Down syndrome cases seem to arise from nondisjunction during meiosis. The reason behind this failure of chromosomes to segregate normally in older women is unclear. In females, meiosis actually begins in the fetus. All developing eggs go through the first round of prophase, including recombination. Meiosis in future egg cells then stops in a stage called diplotene, the stage of crossing-over where homologous chromosomes are hooked together and are in the process of exchanging parts of their DNA. Meiosis doesn't start back up again until a particular developing egg is going through the process of ovulation. At that point, the egg completes the first round of meiosis and then halts again. When sperm and egg unite, the nucleus of the egg cell finishes meiosis just before the nuclei of the sperm and egg fuse to complete the process of fertilization. (In human males, meiosis begins in puberty, is ongoing and continues without pauses like those that occur in females.)

Roughly 75 percent of the nondisjunctions responsible for Down syndrome occur during the first phase of meiosis. Oddly, most of the chromosomes that fail to segregate seem also to have failed to undergo crossing-over, suggesting that the events leading up to nondisjunction begin early in life. Scientists have proposed a number of explanations for the cause of nondisjunction and its associated lack of crossing-over, but no agreement has been reached about what actually happens in the cell to prevent the chromosomes from segregating properly.

Every pregnancy is an independent genetic event. So although age is a factor in calculating risk of trisomy 21, Down syndrome with previous pregnancies doesn't necessarily increase a woman's risk of having another child affected by the disorder.

Some environmental factors have been implicated in Down syndrome that may increase the risk for younger women (less than 30 years of age). Scientists think that women who smoke while on oral contraceptives (birth control pills) may have a higher risk of decreased blood flow to their ovaries. When egg cells are starved for oxygen, they're less likely to develop normally, and nondisjunction may be more likely to occur.

Familial Down syndrome

A second form of Down syndrome, Familial Down syndrome, is unrelated to maternal age. This disorder occurs as a result of the fusion of chromosome 21 to another autosome (often chromosome 14). This fusion is usually the result of a translocation, what happens when non-homologous chromosomes exchange parts. In this case, the exchange involves the long arm of chromosome 21 and the short arm of chromosome 14. This sort of translocation is called a Robertsonian translocation. The leftover parts of chromosomes 14 and 21 also fuse together but are usually lost to cell division and aren't inherited. When a Robertsonian translocation occurs, affected persons can end up with several sorts of chromosome combinations in their gametes.

For Familial Down syndrome, a translocation carrier has one normal copy of chromosome 21, one normal copy of chromosome 14, and one fused translocation chromosome. Carriers aren't affected by Down syndrome because their fused chromosome acts as a second copy of the normal chromosome. When a carrier's cells undergo meiosis, some of their gametes have one translocated chromosome or get the normal complement that includes one copy of each chromosome. Fertilizations of gametes with a translocated chromosome produce the phenotype of Down syndrome. Roughly 10 percent of the liveborn children of carriers have trisomy 21. Carriers have a greater chance than normal of miscarriage due to monosomy (of either 21 or 14) and trisomy 14.


Chromosomal Disorders - abnormalities affecting the chromosomes that result in syndromes (constellations of symptoms) having characteristic physical or functional anomalies. Most chromosomal disorders occur because of alterations in the number of chromosomes or the structure of chromosomes. Though an individual may inherit a chromosomal disorder, more commonly chromosomal disorders represent random occurrences. Typically all the cells in the body reflect the abnormality. Occasionally some but not all cells carry the chromosomal abnormality; this is a mosaic chromosomal disorder. A mosaic presentation tends to be milder than that observed when all cells carry the chromosomal abnormality


Disorders of Replication

Normally chromosomes exist in pairs. Replication errors can result in an incorrect number of chromosomes passing to new cells. Though such errors can occur in any cell with any episode of cell division, they are most harmful when they affect gametes (the sex cells, the ovum in the female and the spermatozoon in the male). Replication err ors in gametes become chromosomal disorders in thenew life created through their union. These errors may take the form of trisomy (an extra CHROMOSOME), monosomy (a missing chromosome), or uniparental disomy (both copies of a chromosome come from the same GAMETE or parent).


Disorders of trisomy occurs when the ZYGOTE receives three instead of the normal two copies of a chromosome. Most trisomies are autosomal, and most autosomal trisomies are lethal very early in embryonic development. Most early losses due to trisomy thus likely escape detection. The survivable autosomal trisomies affect chromosome 13 (PATAU’S SYNDROME), chromosome 18 (EDWARDS SYNDROME), and chromosome 21 (DOWN SYNDROME). Trisomies can also involve the sex chromosomes. The most common such disorder is KLINEFELTER’S SYNDROME, in which the zygote receives two (and sometimes more) X chromosomes and one Y chromosome. Though the Y chromosome determines the gender as male, the additional X chromosome affects sexual development and FERTILITY. The zygote may also receive three X chromosomes (triple X syndrome) or one X chromosome and two Y chromosomes. These trisomies may not produce obvious symptoms, though often boys who have XYY syndrome have developmental delays and learning disabilities.


Monosomy occurs when the zygote receives only one copy of a chromosome andoverall occur far less frequently than trisomy because an entire missing autosome (nonsex chromosome) is nearly always lethal. The monosomy disorder Turner syndrome, in which the zygote receives only one X SEX CHROMOSOME, is one of the few survivable monosomy disorders. Because the single sex chromosome is X, the zygote is female although breast development at sexual maturity is diminished.

Uniparental disomy

In uniparental disomy the zygote receives two copies of a chromosome from one gamete and none from the other gamete. Though in many cases this REPLICATION ERROR may result in no adverse symptoms or consequences, it can allow rare recessive disorders to manifest. Uniparental disomy also causes symptoms when the involved chromosome is one in which GENETIC IMPRINTING is essential. In such circumstances the chromosome pairing requires one chromosome from each parent to activate the chromosome’s genetic functions.

Disorders of Structure

Chromosomal disorders of structure occur when there are physical changes to the chromosome that alter its configuration. In TRANSLOCATION, fragments of a chromosome break away and reattach to other chromosomes or are lost, potentially changing several chromosomes with unpredictable and random results. Inversions, rings, duplications, and deletions are other disorders of structure involving fragments of the chromosome that are fairly uncommon though tend to produce symptoms when they occur. The types of symptoms depend on the involved chromosome.


In a chromosomal inversion the chromosome breaks in two or more locations, then the segments rejoin with one or more segments inverted (upside-down). Some genetic material may be lost in the process, and the genes are out of position. Inversions may or may not cause symptoms, depending on the involved chromosome and the degree of inversion.


Chromosomal rings occur when the ends of the chromosome are missing and the remaining chromosome reshapes itself into a ring. The extent and nature of symptoms depends on the involved chromosome and the amount of missing genetic material. A ring of chromosome 15, for example, tends to produce symptoms such as facial anomalies and growth deficiency.

Duplications and deletions

In duplications and deletions, the chromosome acquires (duplication)or loses (deletion) fragments of its structure. The severity of the consequences depends on the chromosome involved and the extent of the altered genetic material.


Symptoms and Diagnostic Path

The symptoms of chromosomal disorders vary with the chromosome involved and the extent of damage present. Because chromosomal disorders tend to affect large segments of genetic material, the resulting symptoms and syndromes are often complex and affect multiple organs, structures, functions, and systems. The diagnostic path may include imaging procedures such as ULTRASOUND, COMPUTED TOMOGRAPHY (CT) SCAN, and MAGNETIC RESONANCE IMAGING (MRI) to evaluate structural anomalies of internal organs. A KARYOTYPE (picture of the chromosomes a in a cell) reveals overt chromosomal problems, and molecular studies may be necessary to unravel the circumstances of less obvious chromosomal disruptions.

Treatment Options and Outlook

For nearly all chromosomal disorders, treatment focuses on improving physical anomalies and maintaining function to the extent possible. Children born with chromosomal disorders often require ongoing medical care and other kinds of support. Outlook and QUALITY OF LIFE vary widely even within the same syndrome.

Risk Factors and Preventive Measures

Most chromosomal disorders are random events for which there are no preventive measures. Parental age and exposure to teratogenic substances (chemicals, drugs, or other materials that disrupt embryonic or fetal development) are risk factors for certain chromosomal disorders. Doctors recommend all women of childbearing age who could become pregnant, whether or not they are planning PREGNANCY, take folic acid supplementation, which appears to reduce the risk for numerous congenital anomalies and perhaps chromosomal damage.





Mosaic comes from the Greek word mouseios which means of the muses, artistic

When somebody talks about trisomy, or partial trisomy they mean that as far as anyone can tell the chromosomal anomaly occurs in every cell of the body.With mosaicism there is a chromosomal anomaly, but not in every cell. Some cells have the "normal" complement and arrangement of chromosomes and some cells have the chromosomal anomaly.

The effect of mosaicism is wide and variable. Effected individuals can have all of the problems associated with the "full" variant of the chromosomal anomaly or none and anywhere in between.

Some people also feel that if an individual has a mosaic chromosomal anomaly that they do not have the physical problems and or cognitive problems of those who have a "full" version of the chromosomal anomaly. Sadly this is not the case.

Children with a mosaic diagnosis have just as much risk of early death as those with a "full" diagnosis. It is not the chromosomal anomaly itself which causes the early death of our children but how the changes in the genetic material effects the developing baby. Children with a mosaic diagnosis are just as likely to have life threatening cardiac problems, apneas, feeding problems and other potentially life threatening or life shortening congenital problems.


Karyotype Test


Karyotype is a test to identify and evaluate the size, shape, and number of chromosomes in a sample of body cells. Extra, missing, or abnormal positions of chromosome pieces can cause problems with a person's growth, development, and body functions.

Why It Is Done

Karyotyping is done to:

  • Determine whether the chromosomes of an adult have an abnormality that can be passed on to a child.

  • Determine whether a chromosome defect is preventing a woman from becoming pregnant or causing miscarriages.

  • Determine whether a chromosome defect is present in a fetus. Karyotyping also may be done to determine whether chromosomal problems may have caused a fetus to be stillborn.

  • Determine the cause of a baby's birth defects or disability.

  • Help determine the appropriate treatment for some types of cancer.

  • Identify the sex of a person by determining the presence of the Y chromosome. This may be done when a newborn's sex is not clear.

How To Prepare

No special preparation is needed before having this test.

Talk to your doctor about any concerns you have about the need for the test, its risks, or how it will be done. To help you understand the importance of this test, fill out the medical test information form(What is a PDF document?).

Since the information obtained from karyotyping can have a profound impact on your life, you may want to see a doctor who specializes in genetics (geneticist) or a genetic counselor. This type of counselor is trained to help you understand what karyotype test results mean for you, such as your risk for having a child with an inherited (genetic) condition like Down syndrome. A genetic counselor can help you make well-informed decisions. Ask to have genetic counseling before making a decision about a karyotype test.

How It Is Done

Karyotype testing can be done using almost any cell or tissue from the body. A karyotype test usually is done on a blood sample taken from a vein. For testing during pregnancy, it may also be done on a sample of amniotic fluid or the placenta.

Blood sample from a vein

The health professional drawing your blood will:

  • Wrap an elastic band around your upper arm to stop the flow of blood. This makes the veins below the band larger so it is easier to put a needle into the vein.

  • Clean the needle site with alcohol.

  • Put the needle into the vein. More than one needle stick may be needed.

  • Attach a tube to the needle to fill it with blood.

  • Remove the band from your arm when enough blood is collected.

  • Apply a gauze pad or cotton ball over the needle site as the needle is removed.

  • Apply pressure to the site and then a bandage.

Cell sample from a fetus

For this type of test, cells are collected from the fetus using amniocentesis or chorionic villus sampling. For more information about amniocentesis, see the topic Amniocentesis or Chorionic Villus Sampling.

Cell sample from bone marrow

Bone marrow aspiration may be used for a karyotype test. For more information about how this test is done, see the topic Bone Marrow Aspiration and Biopsy.



Karyotype is a test to identify and evaluate the size, shape, and number of chromosomes in a sample of body cells.

Results of a karyotype test are usually available within 1 to 2 weeks.


  • There are 46 chromosomes that can be grouped as 22 matching pairs and 1 pair of sex chromosomes (XX for a female and XY for a male).

  • The size, shape, and structure are normal for each chromosome.


  • There are more than or less than 46 chromosomes.

  • The shape or size of one or more chromosomes is abnormal.

  • A chromosome pair may be broken or incorrectly separated.

What Affects the Test

If you are being treated for cancer, the results of a karyotype test may not be accurate. Chromosomes may be damaged by some types of cancer treatment.

What To Think About

  • Sometimes a karyotype test is combined with other genetic tests to provide more specific information about genetic problems. For more information, see the topic Genetic Test.

  • If the results of karyotype are abnormal, other family members may be advised to undergo testing.

  • A sample taken by gently swabbing the tissues inside the cheek (called a buccal swab) sometimes is used for a karyotype test. But results from buccal swabbing are less accurate than other types of karyotype tests.

  • Since the information obtained from karyotyping can have a profound impact on your life, you may want to see a doctor who specializes in genetics (geneticist) or a genetic counselor. This type of counselor is trained to help you understand what karyotype test results mean for you, such as your risk for having a child with a condition like Down syndrome that is caused by a chromosome problem. A genetic counselor can help you make well-informed decisions. Ask to have genetic counseling before making a decision about a karyotype test.

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