An update on the molecular genetics of congenital adrenal hyperplasia: diagnostic and therapeutic aspects.

An update on the molecular genetics of congenital adrenal hyperplasia due to 21-hydroxylase deficiency is given. In Sweden, direct mutation detection has been used for genetic diagnosis of this disease since 1990. Around 400 affected 21-hydroxylase genes have been analyzed so far. Mutations that have arisen by interaction with the adjacent pseudogene, including gene deletion and nine smaller sequence aberrations, 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%. Some of these rare mutations are present in the pseudogene at a low frequency, indicating that they have started to spread at a low rate in the population. 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 overtreatment can be avoided in mildly affected cases.