Molecular genetics of congenital adrenal hyperplasia (21‐hydroxylase deficiency): implications for diagnosis, prognosis and treatment

The molecular genetics of congenital adrenal hyperplasia due to 21‐hydroxylase deficiency are reviewed. In Sweden, mutation detection based on allele‐specific PCR has been used for genetic diagnosis of this disease since 1993. Around 400 affected 21‐hydroxylase genes have been analysed so far. An update of the spectrum of mutations among the Swedish patients shows that nine common pseudogene‐derived mutations are responsible for the disease in around 95% of alleles. A total of 13 rare, mostly population‐specific mutations have been characterized among the remaining 5%. The mutations can be divided into different groups according to severity. This makes it possible to predict clinical outcome in affected subjects based on genotyping. The risk of salt‐wasting and prenatal virilization can be estimated, and over‐treatment can be avoided in mildly affected cases.