If chromosomes are the body’s instruction books, a translocation is a printing error where a page from one book is stuck into another. A Robertsonian translocation is a specific version of this error where two entire chromosomes fuse together. This event, affecting about 1 in 1,000 newborns, rearranges genetic material. When this results in a person having the correct amount of genetic material, it is a balanced translocation; an “unbalanced” amount, however, can influence health and development.
The Genetic Mechanism of Formation
Robertsonian translocations exclusively involve “acrocentric” chromosomes: 13, 14, 15, 21, and 22. Acrocentric chromosomes have a centromere located very near one end, giving them one long “q” arm and one very short “p” arm. The short arms contain repetitive genetic information, so their loss does not cause health problems.
The translocation occurs when two acrocentric chromosomes break at their centromeres. The long arms fuse to form a single, large chromosome, while the short arms are lost. A person who inherits this fused chromosome along with the normal single copies of the two involved chromosomes has a “balanced” translocation. Although they have 45 chromosomes instead of 46, they possess all necessary genetic material and are healthy and often unaware of their condition.
The issue arises during meiosis, the process that creates eggs and sperm. For a carrier of a balanced translocation, the fused chromosome and the two normal chromosomes can be distributed unevenly into reproductive cells. This can result in gametes having an extra or missing copy of a chromosome. This incorrect segregation sets the stage for an “unbalanced” translocation in an embryo.
Resulting Health Conditions
An unbalanced Robertsonian translocation means an embryo inherits an incorrect amount of genetic material—either too much (trisomy) or too little (monosomy). Monosomy, a missing chromosome copy, is almost always incompatible with life and leads to early miscarriage. The health conditions seen in live births are the result of a trisomy, where there are three copies of a chromosome’s long arm instead of two.
The most well-known condition is Translocation Down Syndrome, which occurs when the translocation involves chromosome 21. A common example is a fusion between chromosomes 14 and 21. An individual with this condition has two normal copies of chromosome 21 plus an additional long arm of chromosome 21 attached to chromosome 14. This results in the features and health issues of Down syndrome, identical to those of standard Trisomy 21.
A rarer condition is Patau syndrome, caused by a translocation involving chromosome 13, resulting in trisomy 13. Patau syndrome is associated with severe intellectual disability and physical abnormalities, and survival beyond the first year is uncommon. Trisomies involving the other acrocentric chromosomes (14, 15, and 22) are not compatible with a full-term pregnancy and result in miscarriage.
Diagnostic Procedures
Diagnosis is made through a karyotype analysis, which is a picture of a person’s chromosomes from a blood sample. The chromosomes are organized into pairs and examined under a microscope. An unbalanced translocation karyotype reveals 46 chromosomes, but with one being the large, fused chromosome and an extra copy of one of the involved chromosomes. For example, a female with Translocation Down syndrome from a 14;21 fusion would have a karyotype written as 46,XX,rob(14;21),+21.
These conditions can also be diagnosed before birth using prenatal procedures like chorionic villus sampling (CVS) or amniocentesis. CVS samples tissue from the placenta between 10 and 13 weeks of gestation. Amniocentesis draws amniotic fluid containing fetal cells between 15 and 20 weeks of pregnancy. Both procedures carry a small risk of miscarriage but allow for a fetal karyotype to be created to see the baby’s chromosomal makeup.
Reproductive Risks and Genetic Counseling
The main reproductive concern is for healthy carriers of a balanced translocation who can produce unbalanced eggs or sperm. When a carrier plans to have children, there are several possible outcomes for a pregnancy:
- The child could inherit a completely normal set of 46 chromosomes.
- The child could inherit the balanced translocation and be a healthy carrier like the parent.
- The pregnancy could result in a child with an unbalanced translocation, leading to a condition like Down or Patau syndrome.
- The pregnancy could end in miscarriage due to a lethal genetic imbalance.
The specific risk percentages depend on which chromosomes are fused and the sex of the carrier parent. A female carrier of a 14;21 translocation has a 10-15% risk of having a child with Translocation Down syndrome, while the risk for a male carrier is about 1-3%. For the most common translocation, rob(13;14), the risk of having a child with Patau syndrome is about 1%.
Genetic counseling provides a personalized risk assessment based on the specific translocation and family history. Counselors explain the genetic information and discuss family planning options. These options may include prenatal diagnosis (CVS or amniocentesis) to determine the fetus’s chromosomes. For couples using in vitro fertilization (IVF), preimplantation genetic testing (PGT) can screen embryos for chromosomal balance before transfer.