The current state of diagnostic genetics for conditions affecting sex development

Abstract

Disorders of sex development (DSD), are a group of rare congenital conditions. Unlike 46, XX DSD where the cause is usually clear, identification of a cause of XY DSD is often unclear and may be attributed to a disorder of gonadal development, androgen synthesis or androgen action. Reaching a firm diagnosis is challenging and requires expertise within a framework that abides by the highest standards of clinical care. Whilst conditions associated with altered sex development have improved our fundamental understanding of sex and gonadal development, it is debatable whether this improvement in our understanding has improved the lives of people with DSD. Thus, there is a need for more emphasis on showing that a firm diagnosis for conditions associated with DSD is associated with a change in clinical practice that benefits the patient. With the rapid advances in diagnostic technology, there is also a need for clearer guidance on the relative merits of biochemical vs genetic evaluation. The standardization and harmonization of complex genetic and biochemical analyses for rare conditions are issues that require further guidance and it is probably that international networks and registries for rare conditions will facilitate the development of this framework.

Keywords: DSD; biochemistry; diagnosis; genitalia; rare disease.