Rare missense CYP17A1 mutations minimally disrupt 17-hydroxylase activity but cause isolated 17,20-lyase deficiency (ILD), Mutations in the POR gene encoding the required cofactor protein cytochrome P450-oxidoreductase causes a spectrum of disease from ILD to 17OHD combined with 21-hydroxylase and aromatase deficiencies, sometimes including skeletal malformations.