SRY -negative disorder of sex development in two biological brothers with SOX3 mutations

46,XX testicular disorder of sex development (DSD) is a rare condition most often caused by translocation of the SRY gene; however, sex-determining region Y (SRY)-negative cases have been associated with SOX3 (SRY-box transcription factor 3) gene duplication. In this case report, the authors report two biological brothers with phenotypic male presentation who were both found to have a 46,XX karyotype, absence of SRY, and SOX3 duplication. Both presented with hypospadias and normal pubertal testosterone levels for age. These are the first reported familial cases of SRY -negative 46,XX testicular DSD caused by SOX3 duplication, supporting a potential heritable mechanism. Long-term follow-up is needed to determine fertility potential and gonadal tumor risk.