Is the 14:21 translocation associated with Down Syndrome a Robertsonian (chromosomal abnormality) or a balanced translocation?

The 14:21 Translocation Associated with Down Syndrome is a Robertsonian Translocation

The 14:21 translocation associated with Down syndrome is definitively a Robertsonian translocation, not a balanced translocation. According to the American College of Medical Genetics guidelines, Down syndrome can be caused by the presence of an extra copy of chromosome 21, either as a free chromosome, a Robertsonian translocation, or as a reciprocal translocation involving chromosome 21 1.

Understanding Robertsonian Translocations in Down Syndrome

Robertsonian translocations are a specific type of chromosomal rearrangement that occurs when the long arms of two acrocentric chromosomes fuse at the centromere with loss of the short arms. In the context of Down syndrome:

• Approximately 5% of Down syndrome cases carry a Robertsonian translocation involving chromosome 21 1
• The most common Robertsonian translocation in Down syndrome is t(14;21) 2
• Other Robertsonian translocations involving chromosome 21 (such as 21;21) are rarer but do occur 2

Key Characteristics of 14:21 Robertsonian Translocations

The 14:21 Robertsonian translocation has specific molecular features:

• The breakpoint typically occurs between specific DNA sequence domains in the p11 region of chromosome 14 3
• The translocation retains certain satellite DNA sequences (pTRS-47) while losing others (pTRS-63) 3
• The centromeric alphoid sequences of both chromosomes 14 and 21 are typically preserved in the translocation 3

Clinical Significance and Inheritance Patterns

Understanding the type of translocation has important implications for genetic counseling:

• If a parent carries a Robertsonian translocation involving chromosome 21, the risk to offspring depends on the sex of the carrier parent 1
• Robertsonian translocations can arise de novo or be inherited from a carrier parent 2
• In rare cases, mosaicism for different Robertsonian translocations can occur, complicating the clinical picture 4, 5

Distinction from Balanced Translocations

It's important to distinguish Robertsonian from balanced reciprocal translocations:

• Robertsonian translocations involve fusion at the centromere with loss of short arms
• Balanced reciprocal translocations involve exchange of material between non-homologous chromosomes without loss of genetic material
• Microarray testing cannot identify balanced chromosomal rearrangements or differentiate free trisomies from unbalanced Robertsonian translocations 1

Diagnostic Considerations

When evaluating for Down syndrome due to translocation:

• Karyotyping remains essential for detecting Robertsonian translocations 1
• FISH and molecular techniques can confirm the specific translocation and determine parental origin 4, 6
• CMA (chromosomal microarray) testing has limitations in detecting balanced rearrangements 1

The identification of a Robertsonian translocation in a patient with Down syndrome should prompt parental karyotyping to determine if the translocation is inherited or de novo, as this significantly impacts recurrence risk for future pregnancies.