46,XY monozygotic twins with discordant sex phenotype

Objective: To analyze male and female sex differentiation in monozygotic twins. Design: Retrospective study. Setting: Multiple academic centers. Patient(s): A pair of monozygotic twins. Intervention(s): Skin and blood samples were obtained for DNA analysis and karyotyping. Main Outcome Measure(s): Mutation within the SRY gene was analyzed by the polymerase chain reaction–single-stranded conformation polymorphism test. Monozygosity was ascertained by short tandem repeat analysis. Karyotypes were studied in blood and skin fibroblasts. Result(s): SRY was present in both twins, but no mutations were detected in the SRY conserved motif. Monozygosity was confirmed by the use of short tandem repeat analysis in four loci: c- fms, thyroid peroxidase, von Willebrand factor, and tyrosine hydroxylase. The karyotype was 46,XY uniformly in both twins. Conclusion(s): Monozygotic twins can develop discordant male and female phenotypes despite the presence of a common karyotype and despite the presence of intact testis-determining genes. In the present case, this could be due to mutation or to mosaicism involving occult 45,X cell lines in the dysgenetic gonads.