A Case with Bladder Exstrophy and Unbalanced X Chromosome Rearrangement

Abstract

Introduction Bladder exstrophy is a rare congenital malformation of the bladder and is believed to be a complex disorder with genetic and environmental background. We describe a young adult female with an isolated bladder exstrophy and with an X chromosome aberration.

Patients and Methods Karyotyping identified an X chromosome rearrangement that was further characterized with array comparative genomic hybridization (CGH) and confirmed by multiplex ligation–dependent probe amplification and fluorescence in situ hybridization (FISH) analysis.

Results The identified X chromosome rearrangement in our index patient consists of a gain of chromosomal material in region Xq26.3- > qter and loss in region Xp22.12- > pter. This aberration was also carried by her mother and sister, none with bladder exstrophy. All three have a disproportionate short stature, as expected due to the deletion of one of the copies of the SHOX gene on Xp22.3. X-inactivation studies revealed a complete skewed inactivation pattern in carriers. Crossover events in the maternal germline furthermore resulted in different genetic material on the rearranged X chromosome between the index patient and her sister.

Conclusion Our findings suggest an X-linked genetic risk factor for bladder exstrophy.

Keywords

array-CGH - bladder exstrophy - MID1 - SHOX - X chromosome rearrangement

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