Genetische basis, terminologie en het risico voor de ontwikkeling van kiemceltumoren bij stoornissen in de geslachtsontwikkeling

In recent years, considerable progress has been made in the characterization of genes involved in normal sex development, and in how mutations in these genes may lead to abnormalities in this process. Moreover, promising results have been obtained in the research concerning the development of germ cell tumors in these patients. At the same time, the commonly used nomenclature and classification system describing the various forms of disorders of sex development has been revised. This article summarizes our actual knowledge with regard to normal sex development and the various genes that are involved in this process and describes how mutations in these genes may lead to a disturbed process of sex development. The renewed nomenclature and classification system, which are in use since 2006, are explained; finally the risk for the development of germ cell tumors in patients with disorders of sex development is discussed, and it is shown how recent research has offered tools to estimate the risk in the individual patient. Psychological research is increasingly emphasizing the importance to consider male gender identity wherever possible in cases of severe undervirilization. Patient advocacy groups demand a more conservative approach with regard to gonadectomy. Medical doctors, scientists, as well as governmental instances are increasingly interested in the development of international research protocols and collaborations in order to optimize the management of patients with disorders of sex development in the future. As a consequence, it is expected that new guidelines for the optimal care of these patients will be proposed in the coming years.