Chromosomal Translocation: Definition, Causes, History, Symptoms, Treatment and Clinical Utility

In genetics, it is an abnormality caused by the rearrangement of parts between non-homologous chromosomes.

A translocation means that there is an unusual arrangement of the chromosomes. This can happen because a change has occurred during the manufacture of the egg or sperm or at the time of conception. An altered chromosome arrangement has been inherited from either the mother or the father.

A gene fusion can be created when the translocation joins two otherwise separate genes, is detected in cytogenetics or a karyotype of affected cells.

Chromosomal translocations are one of the most common types of genetic rearrangements and are molecular signatures for many types of cancer. They are considered leading causes of cancers, especially lymphoma and leukemia.

Translocations can be balanced (in a uniform exchange of material with no additional or missing genetic information, and ideally with full functionality) or unbalanced (where the exchange of chromosomal material is uneven and extra or missing genes are obtained).

Often a child can be born with a translocation, although the chromosomes of both parents are normal. This is called de novo (from Latin) or new reorganization. In this case, the parents are unlikely to have another child with a translocation.

What are the causes of translocations?

Although about 1 person in 500 has a translocation, we still don’t understand why they occur. Although many translocations have been reported in the past four decades, the mechanism by which chromosomes break during a translocation remains largely unknown.


In 1914, Theodor Boveri first hypothesized that genetic aberrations could be the underlying cause of cancer. However, it took almost 50 years for the first chromosomal translocation to be discovered in any form of cancer.

In 1938, Karl Sax , at the Biological Laboratories of Harvard University, published a work entitled: “X-ray Induced Chromosomal Aberrations”, which showed that radiation could induce important genetic changes by affecting chromosomal translocations.

The document is believed to mark the beginning of the field of radiation cytology and led to it being called “the father of radiation cytology.”

Reciprocal translocations

Reciprocal translocations are usually an exchange of material between non-homologous chromosomes. It is a condition in which part of a chromosome has been broken and reattached in another location.

In other words, it means that sections of two chromosomes have switched places. Incidence estimates range from approximately 1 in 500 to 1 in 625 human newborns.

Such translocations are generally harmless and can be found through prenatal diagnosis. However, they can cause serious health problems, depending on the circumstances.

Carriers of balanced reciprocal translocations are at increased risk of creating gametes with unbalanced chromosomal translocations, leading to miscarriages or abnormal children.

In the case of the former (harmless translocations), many people can have translocations without being aware of the condition.

This is usually the case for reciprocal (or balanced) translocation, a type of chromosomal translocation that increases the risk of recurrent miscarriages. Genetic counseling and genetic testing are often offered to families who can carry out a translocation.

What does a balanced translocation mean

In a balanced translocation, a person generally has all the genetic material necessary for normal growth – one piece of a chromosome simply breaks off and joins another.

However, when that person’s cells divide to create an egg or sperm for reproduction, the egg or sperm cells can end up with additional genetic material or lost genetic material, which could lead to a miscarriage depending on the chromosome and the cells. affected genes.

Balanced translocation symptoms

Most balanced translocation carriers are healthy and do not have any symptoms, but about 6% of them have a variety of symptoms that can include autism, intellectual disability, or birth defects.

An altered or dysregulated gene at the breakpoint of the translocation transporter is likely the cause of these symptoms.

It is important to distinguish between the chromosomal translocations that occur in gametogenesis, due to errors in meiosis, and the translocations that occur in the cell division of somatic cells, due to errors in mitosis.

The former results in a chromosomal abnormality present in all cells of the offspring, as in translocation carriers.

Somatic translocations, on the other hand, result in abnormalities present only in the affected cell line, as in chronic myelogenous leukemia with the Philadelphia chromosome translocation.

Incidence of recurrent miscarriages

In about 4.5 percent of all couples with recurrent miscarriages, one or both parents have a balanced translocation.

Research has shown that couples with balanced translocations are more likely to have miscarriages than couples without balanced translocations.

There is some evidence that balanced translocations involving specific chromosomes are more likely to cause miscarriages than others.

Non-reciprocal translocation

Non-reciprocal translocation involves the transfer of genes from one chromosome to another non-homologous chromosome.

Translocaciones Robertsonianas

Robertson’s translocation is a type of translocation caused by breaks at or near the centromeres of two acrocentric chromosomes.

The reciprocal exchange of parts results in a large metacentric chromosome and an extremely small chromosome that can be lost from the body with little effect because it contains so few genes.

The resulting karyotype in humans leaves only 45 chromosomes, as two chromosomes were fused. This does not have a direct effect on the phenotype, since the only genes in the short arms of the acrocentric ones are common to all of them and are present in a variable copy number (nucleolar organizing genes).

Robertsonian translocations involving all acrocentric chromosome combinations have been seen. The most common translocation in humans involves chromosomes 13 and 14 and is seen in approximately 0.97 / 1000 newborns.

Carriers of Robertsonian translocations are not associated with any phenotypic abnormalities, but there is a risk of imbalanced gametes causing miscarriage or abnormal offspring .

This is due to poor segregation (nondisjunction) during gametogenesis. Robertsonian translocations involving chromosome 14 also carry a slight risk of uniparental disomy 14 due to trisomy salvage.

When could this cause problems?

A person who carries a balanced translocation is generally unaffected by it and is often unaware of having it. The only time it can be important is when he or she gets to have children.

Role in disease

The severity of the disability depends on exactly which parts the chromosomes are involved and the amount of extra or missing chromosomal material. Some human diseases caused by translocations are:

Cancer : various forms of cancer are caused by acquired translocations (as opposed to those present from conception); this has been described mainly in leukemia (acute myelogenous leukemia and chronic myelogenous leukemia).

Translocations have also been described in solid malignancies such as Ewing’s sarcoma.

Infertility : one of the potential parents carries out a balanced translocation, where the father is asymptomatic but the conceived fetuses are not viable.

Down syndrome is caused in a minority (5% or less) of cases by a Robertsonian translocation of the long arm of chromosome 21 into the long arm of chromosome 14.

Male XX syndrome : caused by a translocation of the Y chromosome sex determination region (SRY) gene from the Y chromosome to the X chromosome.

By chromosome


The International System for Human Cytogenetic Nomenclature (ISCN) is used to denote a translocation between chromosomes. The designation t (A; B) (p1; q2) is used to denote a translocation between chromosome A and chromosome B.

The information in the second set of parentheses, when given, provides the precise location within the chromosome for chromosomes A and B, respectively, where p indicates the short arm of the chromosome, q indicates the long arm, and the numbers after p or q are refer to regions, bands, and subbands observed when the chromosome is stained with a staining dye.

Translocation is the mechanism that can cause a gene to move from one linking group to another.

If a parent has a balanced translocation, will he or she always pass it on?

Not necessarily, there are several possibilities for each pregnancy:

  • The child can inherit completely normal chromosomes.
  • The child can inherit the same balanced translocation as the father. In most cases, the child will not have any problems as a result of the translocation.
  • The child can inherit an unbalanced translocation and can be born with some degree of developmental delay, learning problems, and health problems.
  • The pregnancy ends in miscarriage.

Chromosomal translocation tests

Genetic testing is available to find out if a person carries out a translocation. A simple blood test is performed and the blood cells are examined in a laboratory to look at the arrangement of the chromosomes.

This is called a karyotype test. Some research suggests that balanced translocation in the mother is more likely to be associated with recurrent miscarriages, but the parents can also be carriers.

It is also possible to do a test during pregnancy to look for if a baby has a chromosome translocation. This is called prenatal diagnosis and is something you may want to discuss with your geneticist.


There is no cure for balanced translocation, and in most cases, the only adverse health effect is recurrent miscarriage.

For couples affected by balanced translocation, the odds are in favor of a successful pregnancy at some point, but repeated miscarriages can obviously be difficult to deal with emotionally.

Recurrent miscarriages can also have physical consequences. For some women, repeated miscarriages can cause complications, such as a build-up of scar tissue after a D&C.

Consequently, couples with a known and balanced translocation who fear both the emotional trauma and the physical trauma that repeated pregnancy loss can cause may want to explore more high-tech means of carrying a pregnancy to term.

High-tech treatments

In some cases, couples with balanced translocation may opt for a treatment called preimplantation genetic diagnosis (PGD).

In preimplantation genetic diagnosis, the couple conceives through in vitro fertilization along with genetic testing of the embryos to ensure that they do not have an unbalanced translocation.

However, preimplantation genetic diagnosis and IVF are very expensive and not covered by insurance most of the time, which is another reason why many couples are forced to keep trying without intervention.

That said, you may be able to get loans to help pay for these procedures, apply for grants for couples needing IVF or save the money yourself, and report your medical expenses as a tax deduction if they exceed 10 percent of your gross income. tight.

What about other family members?

If a translocation is found, that person may wish to discuss this with other family members. This gives other family members the opportunity to have a blood test to see if they also carry out the translocation, if they wish.

Some people find it difficult to tell other family members about the translocation. They may be concerned about causing anxiety in the family. In some families, people have lost contact with relatives and may feel that it is difficult to contact them.

Clinical utility of chromosomal translocations

The clinical importance of recurrent chromosomal translocations in patients with hematologic malignancies has been underscored by the use of these translocations to tailor treatment for patients with leukemia and lymphoma.

For example, almost all patients with translocation chronic myeloid leukemia (9; 22) show dramatic responses to imatinib, a recently developed tyrosine kinase inhibitor, and to the treatment of those with acute myeloid leukemia (AML). ) that have a (15; 17) translocation with all trans retinoic acids results in complete remission in a high percentage of patients.

These are specific therapies directed toward a tyrosine kinase fusion (BCR-ABL) and a retinoic acid receptor fusion (PML-RARA), respectively.

Although these specific targeted therapies are only available for a subset of leukemia patients with specific chromosomal abnormalities, it has been observed that patients with certain translocations respond differently to conventional cytotoxic chemotherapy.

For example, patients with acute myeloid leukemia with an inv (16) or (8; 21) chromosome respond better to high-dose cytarabine than do patients without an inv (16) or ot (8; 21) chromosome.

As a result of these studies, cytogenetic and molecular genetic findings are now an integral factor in determining chemotherapy regimens for the majority of patients with acute leukemia.

Chromosomal translocations have been shown to be causal events involved in the development of many forms of malignancy; The clinical utility of these translocations is highlighted by their use in designing risk-appropriate treatment strategies.

The study of chromosomal translocations has revealed several recurring themes and has provided important insights into the process of malignant transformation. However, the mechanisms that cause these translocations remain elusive.

A deeper understanding of the mechanisms that cause chromosomal translocations will be aided by the continued characterization of translocation breakpoints and the development of in vitro and in vivo model systems that can generate chromosomal translocations.