Functional disomy of Xp including duplication of DAX1 gene with sex reversal due to t(X;Y)(p21.2;p11.3).

Translocations involving the short arms of the X and Y in human chromosomes are uncommon. One of the best-known consequences of such exchanges is sex reversal in 46,XX males and some 46,XY females, due to exchange in the paternal germline of terminal portions of Xp and Yp, including the SRY gene. Translocations of Xp segments to the Y chromosome result in functional disomy of the X chromosome with an abnormal phenotype and sex reversal if the DSS locus, mapped in Xp21, is present. We describe a 7-month-old girl with severe psychomotor retardation, minor anomalies, malformations, and female external genitalia. Cytogenetic analysis showed a 46,X,mar karyotype. The marker was identified as a der(Y)t(Xp;Yp) by fluorescence in situ hybridisation analysis. Further studies with specific locus probes of X and Y chromosomes made it possible to clarify the break points and demonstrated the presence of two copies of the DAX1 gene, one on the normal X chromosome and one on the der(Y). The karyotype of the child was: 46,X,der(Y)t(X;Y)(p21.2;p11.3). The syndrome resulted from functional disomy Xp21.2-pter, with sex reversal related to the presence of two active copies of the DAX1 gene located in Xp21. Few cases of Xp disomy with sex reversal have been reported, primarily related to Xp duplications with 46,XY karyotype, and less often to Xp;Yq translocations. To our knowledge, our patient with sex reversal and a t(Xp;Yp) is the second reported case.