infants are raised as boys and have a presumed or actual XY karyotype.
In these boys, around 50% will have a hypospadias where the urethral meatus is distal; in 35% the urethral meatus will be situated on the penile shaft and in the rest it is sited more proximal. 46, XY DSD is characterized by reduced androgenization and cuases include complete gonadal dysgenesis (CGD) or partial gonadal dysgenesis (PGD) or a defect in androgen synthesis or action.In comparison with infants with 46, XY DSD, who are most likely to be investigated comprehensively and in over 90% of the cases, shall have CAH, many infants with 46, XY DSD and especially those who are raised as boys, are often investigated to a variable extent and the aetiology remains unclear in the majority. Girls with 46,XY DSD will most likely have androgen insensitivity syndrome (AIS), gonadal dysgenesis or a biochemical disorder of androgen synthesis.In 46, XY girls with a clinical diagonosis of AIS, over 80% may have a mutation in Androgen Receptor (AR) gene. However, in 46, XY boys with a DSD, 20-30% may have a mutation in AR.
Thus, the commonest broad group of infants are boys with 46, XY DSD, and in this large group, a confirmed genetic diagonosis remains elusivein 60-70% of the cases.The next broad group of infants are girls with XY DSD who have abnormal gonadal function or androgen synthesis and in the majority of these cases a confirmed genetic diagnosis is also unclear.