Down syndrome is a common chromosomal condition resulting from extra genetic material from chromosome 21. Most cases are caused by Trisomy 21, where every cell contains three separate copies of chromosome 21 instead of the usual two. A small percentage of individuals, however, have the extra material due to a different type of genetic change known as Translocation Down Syndrome (TDS). This less common form involves a unique rearrangement of the chromosomes.
Defining Translocation Down Syndrome
Translocation Down Syndrome (TDS) is a form of the condition where the total number of chromosomes often remains 46, unlike the 47 seen in Trisomy 21. The difference is in the arrangement: a full or partial extra copy of chromosome 21 becomes attached, or translocated, onto another chromosome.
TDS accounts for approximately 3% to 5% of all Down syndrome cases. The most frequent occurrence is the fusion of chromosome 21 material onto chromosome 14, though translocations involving chromosomes 13, 15, or 22 are also observed. Despite the difference in underlying genetics, the clinical presentation of TDS is generally indistinguishable from Trisomy 21. Individuals exhibit the same characteristic physical features and developmental trajectories because the core issue—the presence of three copies of chromosome 21 genes—is the same.
The Mechanics of Chromosomal Rearrangement
The specific rearrangement causing Translocation Down Syndrome is often a Robertsonian translocation. This event occurs between acrocentric chromosomes, which are those where the centromere is located very close to one end. Human acrocentric chromosomes include numbers 13, 14, 15, 21, and 22.
During this process, two acrocentric chromosomes break near their centromeres. Their long arms fuse together to form a single, merged chromosome, while the short arms are lost. In TDS, the long arm of chromosome 21 typically fuses with the long arm of another acrocentric chromosome, most often chromosome 14.
An individual with an unbalanced translocation has two normal copies of chromosome 21, plus the fused chromosome containing the third copy of the chromosome 21 long arm. This results in the genetic material of chromosome 21 being present in triplicate, causing the developmental differences associated with the syndrome, despite the total chromosome count being 46.
Sporadic vs. Inherited Translocation
Translocation Down Syndrome is categorized based on whether the change arose randomly or was inherited. The vast majority of cases (roughly 75%) are de novo, meaning the translocation occurred spontaneously in the sperm, egg, or early embryo development. This sporadic change is not present in either parent’s genetic makeup.
The remaining 25% of cases are inherited from a parent who carries a balanced translocation. A balanced carrier possesses the fused chromosome but has not lost or gained substantial genetic material. These individuals are typically healthy and show no signs of Down syndrome, even though they have only 45 chromosomes in each cell.
The challenge for a balanced carrier arises during the formation of reproductive cells. The rearranged chromosomes can segregate incorrectly, leading to gametes that are either missing genetic material or contain extra material. When an unbalanced gamete is passed to a child, it results in the extra chromosome 21 material that defines TDS.
Recurrence Risk and Genetic Counseling
The probability of having another child with Down syndrome depends heavily on whether the translocation is sporadic or inherited. If the translocation is de novo, the chance of recurrence in a future pregnancy is low, estimated at 2% to 3%. This risk is similar to the general recurrence risk for standard Trisomy 21.
If one parent is identified as a balanced carrier, the recurrence risk is significantly higher and varies by the carrier parent. When the mother carries the translocation involving chromosome 21, the risk of having a child with TDS is approximately 10% to 15%. If the father is the carrier, the observed risk is lower, ranging from 2.5% to 5%.
Determining carrier status requires a blood test called a karyotype. Genetic counseling is an important step for affected families. Counselors interpret the karyotype results, explain the exact nature of the translocation, and provide personalized recurrence probabilities for future pregnancies. They offer guidance on reproductive options and help families make informed decisions.