Prenatal diagnosis of de novo X;autosome translocations

The identification of a de novo apparently balanced structural chromosome rearrangement at prenatal diagnosis can be problematic and raises unique genetic counseling issues. Two breakpoint rearrangements such as reciprocal translocations or inversions have a 6.7% empiric risk of phenotypic abnormality. Abnormal phenotypes are thought to result from gene disruption, position effect, or deletion at one of the breakpoints. Prenatal diagnosis of de novo X;autosome translocations is rare, and presents additional unique risks due to the effects of X-inactivation and the possibility of disruption of the single active copy of an X-linked gene. We report the identification of a de novo apparently balanced t(X;6)(q26;q23) ascertained after amniocentesis for advanced maternal age. The parents were counseled regarding the risk of a de novo apparently balanced translocation, including the potential risk of an X-linked Mendelian disorder resulting from disruption of a gene at the Xq26 breakpoint. While the normal X chromosome was late replicating in all metaphases, no conclusions from this data could be drawn as the X-inactivation ratio in amniocytes might not be representative of other tissues. The possibility of future premature ovarian failure was also noted due to the position of the breakpoint at Xq26, although no specific risk could be ascribed. The parents elected to continue the pregnancy, and at 17 months of age, the proband was phenotypically and developmentally normal. Long-term follow-up will be required to assess development delay and any fertility issues. Based on review of the few cases reported to date and excluding any risk for later reproductive abnormalities, we estimated the risk of phenotypic abnormality or developmental delay in a prenatally ascertained de novo X;autosome carrier to be as high as 50%. This case illustrates the complexities in counseling for prenatally ascertained de novo X;autosome translocations and the need for additional cases to be reported.