Duplication of dosage sensitive sex reversal area in a 46, XY patient with normal sex determining region of Y causing complete sex reversal

Background: The sex chromosome composition of the primordial gonad, either 46XX or 46XY, determines its differentiation as ovaries or testes. Local hormones secreted by developing gonads and tissue specific transcription factors influence the differentiation of external and internal genital structures. Dosage sensitive sex reversal adrenal hypoplasia congenita critical region (DAX1) on Xp21 is a gene which is expressed in the developing adrenals, gonads, hypothalamus and pituitary gland. Duplication of this area causes dosage sensitive male-to-female sex reversal while mutation or deletion leads to adrenal hypoplasia congenita with hypogonadotropic hypogonadism in affected males. Aim: To report a case with duplication of the X chromosome segment within the region of Xp21.1-22.2 resulting in 46 XY sex reversal and a literature review on DAX1 and dosage sensitive sex reversal (DSS). Methods and results: We present the clinical history, physical findings, laboratory, and imaging study results in a newborn baby. This infant was sex assigned as female at birth and had normal female external genitalia. Chromosome analysis was done due to multiple minor malformations and showed a karyotype of 46 Xp+Y. Fluorescent in situ hybridization analysis revealed the duplication in the DSS area. Conclusion: Duplication of the DAX1 gene on the X chromosome with normal sex determining region of Y (SRY) results in 46 XY sex reversal. This was inherited from the mother who had normal ovarian function. Additional problems include growth failure, mental retardation and multiple congenital anomalies. The baby did not have a mutation or deletion of DAX1, which would have caused adrenal insufficiency and hypogonadism.