Upon review of the karyotype of tissue from the previous pregnancy loss, the marker chromosome that was seen most likely represents a derivative 13 chromosome. This likely resulted from abnormal segregation of the chromosomes during gametogenesis. As a result, the karyotype for the products of conception was amended. It was ultimately signed out as a female karyotype with a maternally inherited unbalanced chromosome rearrangement resulting in partial trisomy 13 and partial trisomy 7. The marker chromosome is composed of chromosomal segments 13pter 13q14.1 and 7q34 7qter. The derivative chromosome along with the normal complement of two chromosome 7's and two chromosome 13's result in a partial trisomy for each.
See diagrams below for mechanism of creation for this product of conception's unstable karyotype.
A variety of gametes could theoretically be produced during gametogenesis; however, it is important to note that studies have shown that not all gametes that are possible actually occur in similar frequencies. The above segregation pattern along with the first three below are examples of 3:1 segregation patterns (where 3 of the chromosomes involved in a balanced translocation segregate to one gamete during meiosis I, and the last chromosome segregates to the other gamete); the following three are examples of 2:2 segregation patterns (where 2 of the chromosomes involved in a balanced translocation segregate to one gamete during meiosis I, and the other 2 chromosomes segregate to the other gamete).
Chromosomal analysis was extremely useful in the workup of this patient with recurrent miscarriages. Since gametes in patients with balanced translocations are not created or survive in equal proportions, the possibility of a relatively high number of unfavorable pregnancy outcomes due to a higher proportion of unbalanced gametes exists. This has complex implications for genetic counseling of the patient with a balanced translocation that is trying to conceive. If this patient (or similar patients) wishes to have more children, counseling the patient on relative frequencies of gametes that could be inherited along with associated outcomes is key. If conception is successful, monitoring of the fetus with early second trimester amniocentesis, chorionic villus sampling, or high-resolution ultrasound is recommended. Again, in any patient with any balanced translocation, counseling the patient on fetal outcomes is vital.
AT Midro et al. Risk evaluation of carriers with chromosome reciprocal translocation t(7;13)(q34;q13) and concomitant meiotic segregation analyzed by FISH on ejaculated spermatozoa. American Journal of Medical Genetics. 2006; 140(3): 245-256.
SL Gersen and MB Keagle. Principles of Clinical Cytogenetics. Humana Press, 2nd ed. 2004.
Contributed by Jay S. Raval, MD and Urvashi Surti, PhD