Robertsonian translocation: What is it? Mechanism, Consequences and Prenatal Tests

It is a rare form of chromosomal rearrangement. In humans it occurs in the five pairs of acrocentric chromosomes, such as 13, 14, 15, 21 and 22.

Other types of translocations are produced, but they do not lead to a viable fetus.

These translocations are named after the American biologist William Rees Brebner Robertson Ph.D. (1881-1941).

They are also called whole-arm translocations or centric fusion translocations.

Mechanism

Robertsonian translocation (also called central fusion or full-arm fusion) is a type of chromosomal translocation that occurs mainly between acrocentric chromosomes, where the breakpoints are between the short and long arms of two acrocentric chromosomes, which may or may not be homologous

In a balanced way, a Robertsonian translocation simply produces a chromosome fused with the full function of the two acrocentric chromosomes that originated it and, as such, there are no negative phenotypic effects.

However, in unbalanced form, it can lead to an alteration in the number of chromosomes and several syndromes of malformation and mental retardation.

This is due to non-disjunction during gametogenesis, so the mother has a higher risk of transmission (10%) than the father (1%).

A Robertsonian translocation is a type of translocation involving two homologous chromosomes (paired) or non-homologous chromosomes.

A feature of the chromosomes that are commonly found to experience such translocations is that they possess an acrocentric centromere, dividing the chromosome into a large arm that contains the vast majority of genes, and a short arm with a much smaller proportion of genetic content.

During a Robertsonian translocation, the participating chromosomes rupture in their centromeres and the long arms fuse to form a single large chromosome with a single centromere.

Short-arm fusion contains non-essential genes, such as those that encode rRNA, which are still present in multiple copies in the genome, short arms are usually lost after a few rounds of cell division.

Consequence

When a Robertsonian translocation occurs and the long arm of chromosome 21 binds with the long arm of chromosomes 14 or 15, this heterozygous carrier is phenotypically normal since there are two copies of all major chromosomal arms and, therefore, two copies of all the essential genes.

However, the progeny of this carrier can inherit an unbalanced trisomy.

Approximately one in every thousand newborns has a Robertsonian translocation.

The most frequent forms of Robertsonian translocations occur when the long arms of two acrocentric chromosomes fuse in the centromere and the two short arms are lost.

A Robertsonian translocation in a balanced way does not produce excess or deficit of genetic material and does not cause health problems.

In unbalanced forms, Robertsonian translocations cause deletions or chromosomal additions, resulting in syndromes of multiple malformations, which include trisomy 13 (Patau syndrome) and trisomy 21 (Down syndrome).

A Robertsonian translocation occurs, for example, when the long arms of chromosomes 13 and 14 are fused, no significant genetic material is lost, and the person is completely normal despite the translocation.

Most people with Robertsonian translocations have 45 chromosomes in each of their cells, however, all the essential genetic material is present and appear normal.

However, their offspring may be normal and carry the fusion chromosome (depending on which chromosome is represented in the gamete), or they may inherit a missing or extralarge arm from an acrocentric chromosome.

Rarely, the same translocation can be present homozygously if parents heterozygous with the same Robertsonian translocation have children. The result can be a viable offspring with 44 chromosomes.

Of the possible segregates, monosomy 14, trisomy 14 and monosomy 21 are lethal.

The remaining possibilities are a child with normal chromosomes, a child with balanced translocation and a child with Down syndrome due to the unbalanced form of the translocation that causes trisomy 21.

This child has inherited the Robertsonian translocation chromosome 14-21, as well as normal chromosome 21 of the parent carrier, and a normal chromosome 14 and 21 normal chromosome of the other parent.

A parent who is a carrier of a Robertsonian translocation involving chromosome 21 has a high risk of having an affected child with Down syndrome, compared with the low recurrence in regular Down syndrome of trisomy 21 (which is due to an error in cell division, and has a recurrence risk of approximately 1 in 100).

The figures observed for Robertsonian translocation carriers involving chromosome 21 with a baby born with Down syndrome are 10% if the mother is a translocation carrier and 2.5% if the parent is a translocation carrier.

Robertsonian translocations are rearrangements of the acrocentric chromosomes 13-15 and 21-22.

Cytologically, between homologous chromosomes one can not distinguish isochromosomes that originate through the duplication of a single homolog. Both types of rearrangements may be involved in aneuploidy.

Antenatal tests

Prenatal testing should be considered in all pregnancies when one of the parents is a balanced carrier of a Robertsonian translocation due to the risk of aneuploidy.

Uniparental disomy tests should be considered in fetuses that contain a balanced Robertsonian translocation or isochromosome that involves chromosomes 14 or 15.

In addition, infants or children with congenital anomalies who carry a Robertsonian translocation should also be considered for uniparental disomy tests.