Robertsonian translocation | USMLE step 1| Lecture 16

Robertsonian translocations — The acrocentric human chromosomes 13, 14, 15, 21, and 22 have very short p-arms that contain only chromosomal satellites and the genetic code for ribosomal RNAs. Their centromeres, therefore, are very close to one end of the chromosome. When the long arms of two acrocentric chromosomes merge by translocation, their short arms are lost, and, depending upon the location of the breakpoints, a dicentric or monocentric fusion-chromosome is created.

Loss of the short arms of acrocentric chromosomes does not have phenotypic consequences, because the lost sections do not contain unique genetic sequences. The only consequence is a balanced karyotype with 45 instead of 46 chromosomes. This is identified in approximately 1 in 1000 individuals.

However, unbalanced gametes of heterozygous carriers are common and give rise to a monosomic or trisomic fetus. Most monosomies and trisomies are lethal and spontaneously abort early in the pregnancy. Surviving fetuses with trisomy 21, however, can be viable and affected with Down syndrome, although about 85 percent of trisomy 21 conceptuses will not make it to term. When this syndrome is caused by a parental Robertsonian translocation, the carrier parent typically has a fusion of the long arms of chromosomes 14 and 21. One of the three viable gametes will be balanced, one will be normal, and one will contain the fused chromosome [der(14;21)] as well as the unaffected chromosome 21. Normal fertilization of this gamete results in a fetus with trisomy 21. The empiric risk for a child with Down syndrome is 10 to 15 percent for a carrier mother, but only 2 percent if the father carries the Robertsonian translocation.