Androgen insensitivity syndrome.

In a relatively short period of time, understanding of the fundamental causes of androgen insensitivity syndromes has improved dramatically. This has been brought about by the combination of several disciplines, including endocrinology, genetics, developmental and molecular biology. Mutations can be identified in the androgen receptor gene in suspected cases of AIS, and their functional consequences examined in various in-vitro systems. This information can then be correlated with the clinical presentation of the patient, and is beginning to provide an explanation for the highly variable clinical presentation of AIS. It is to be hoped that this information will also help to predict the likely outcome of androgen therapy in infants with PAIS and an intersex phenotype. More speculatively, functional studies may also lead to novel strategies for the treatment of patients. This would then be of enormous benefit to both patient and parents. Furthermore, the identification of a mutation allows precise information for genetic counselling of families affected by AIS. However, many questions still remain to challenge clinicians and scientists alike. These include the risk of testicular malignancy in patients with AIS and currently there is no worldwide consensus on the stage at which testes should be removed from patients reared as female. There are also significant challenges in patient counselling. Although there is greater understanding of the molecular defects that cause AIS, there are several examples of patients with a similar degree of receptor dysfunction, or even the same mutation, but whose phenotypes are widely different. Other factors must therefore contribute to the clinical presentation of AIS, although these have not been identified. Finally, there are the mutations in patients with Kennedy's disease. The consequences of the mutations are unexplained and are a clear indication that there is still a great deal to discover about the function and biology of androgen receptors.