Mr. and Mrs. Smith were evaluated in the genetics clinic due to a history of multiple miscarriages. Chromosome analysis was ordered for both individuals and demonstrated that Mrs. Smith has a chromosomal abnormality (see a representative karyotype below).
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The chromosomal abnormality identified in this patient is an example of a Robertsonian translocation. Robertsonian translocations are the most common type of structural chromosomal abnormality seen in the general population, with an estimated prevalence of 1 per 800-1,000 individuals. This type of translocation results from fusion of the long arms of two acrocentric chromosomes (13, 14, 15, 21, 22). The 13;14 and 14;21 translocations are the most common and account for approximately 85% of all Robertsonian translocations.
The carriers of balanced Robertsonian translocations are phenotypically normal. However, they commonly present with fertility problems, recurrent miscarriages, or children with congenital abnormalities due to an unbalanced form of the translocation, or, in the case of Robertsonian translocation involving imprinted chromosomes (14 and 14), uniparental disomy.
The presence of a chromosomal translocation is often associated with partial or complete spermatogenic arrest, and therefore some male translocation carriers have reduced fertility. In contrast, oogenesis is more likely to progress without an arrest in meiosis despite the presence of a chromosomal translocation. Therefore, the overall risk of having an unbalanced offspring is higher in female carriers compared to male carriers.
The risk of having a liveborn with trisomy 21 in female carriers of the 14;21 Robertsonian translocation is estimated to be 10%-15%, whereas the risk in male carriers is estimated to be 0%-2%.
Katarzyna Thompson, Ph.D.
Fellow, Laboratory Genetics and Genomics
Nicole Hoppman, Ph.D.
Consultant, Laboratory Genetics and Genomics
Associate Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science