True hermaphroditism with ambiguous genitalia due to a complicated mosaic karyotype: clinical features, cytogenetic findings, and literature review

Abnormal recombination between the X and Y chromosomes during meiosis, occurring outside the pseudoautosomal region, can result in translocation of the SRY gene from the Y to the X chromosome, and consequently in abnormal sexual differentiation, such as the development of 46,XX males or true hermaphroditism. In this report we present clinical, cytogenetic, and molecular-cytogenetic data of a patient with ambiguous genitalia and true hermaphroditism, who had a unique mosaic karyotype, comprising three different cell lines: 46,XX(SRY+), 45,X(SRY+), and 45,X. The mosaic karyotype of our patient probably represents two different events: abnormal recombination between the X and Y chromosomes during paternal meiosis, and postzygotic loss of one of the X chromosomes. Replication studies demonstrated that in 80% of the XX cells, the SRY sequence was located on the active X chromosome. This finding suggests nonrandom X inactivation and, together with the presence of the SRY gene, explains the male phenotype of our patient. On the other hand, the presence of the 45,X cell line may have contributed to genital ambiguity. We conclude that fluorescence in situ hybridization (FISH) analysis with SRY probes is highly recommended and allows accurate diagnosis and optimal management in cases of 46,XX hermaphroditism and ambiguous genitalia.