Disorders of sex development: Genetic base, terminology and risk for the development of germ cell tumors

Abstract

In recent years, considerable progress has been made in the characterization of genes involved in normal sex development as well as how mutations in these genes may induce abnormalities during this process. Moreover, promising results have been obtained in 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 (DSD) have been revised. This manuscript summarizes our actual knowledge concerning normal sex development and the various genes involved in this process, while describing how mutations in these genes may induce a disturbed sex development. The revised nomenclature and classification, which are in use since 2006 are explained; finally the risk for the development of germ cell tumors in patients with DSD is discussed, while it is detailed how recent research offers tools estimating the risk in the individual patient. In cases of severe undervirilization, it is emphasized to consider male gender identity, whenever possible. Patient advocacy groups demand a more conservative approach as regards gonadectomy. Medical doctors, scientists, as well as governmental instances are more and more interested in developing international research protocols in order to optimize in the future the management of patients with DSD. As a consequence, it may be expected that new guidelines for the optimal care of these patients will be developed in the coming years.