Following a number of recent reports in which NR5A1, AR and WT1 mutations and CNVs have been identified as the cause of isolated hypospadias and/or cryptorchidism [10,12,33-39], a standardized genetic screening protocol was applied to identify the underlying genetic cause of the observed atypical genital development in all cases where clinical and hormonal data did not suggest a specific diagnosis, irrespective of the EMS scores. This evidence concerns the gene NR5A1 and hypospadias.