Rare missense P450c17 (CYP17A1) mutation in exon 1 as a cause of 46,XY disorder of sexual development: implications of breast tissue 'unresponsiveness' despite adequate estradiol substitution.

17-Alpha-hydroxylase/17,20-lyase deficiency (17OHD) is a rare autosomal recessive disorder resulting from mutations in the CYP17A1 gene, leading to impaired adrenal and gonadal steroidogenesis. We report for the first time a patient with a missense mutation at codon 96 (R96Q) of the CYP17A1 gene causing a 46,XY disorder of sexual development (DSD) that additionally showed lack of breast development despite highly dosed estradiol replacement treatment. This phenomenon could be attributed to irreversible breast tissue alterations following high serum progesterone levels.