Disorders of Sex Determination

Abstract

Human sex determination refers to the processes by which an embryo becomes either a male or a female during development. Advances in developmental and cell biology, molecular genetics, and experimental embryology have greatly helped us to clarify problems of sexual determination and differentiation. The steps of formation of the testes are dependent on a series of Y-linked, X-linked, and autosomal gene actions and interactions. The discovery of the SRY gene (sex-determining region of Y chromosome) in 1990 triggered a revolution in our understanding of sex determination. SRY has a fundamental role in sex determination and is believed to be the switch that initiates testis development from the bipotential gonads. This discovery was followed by a description of several new genes and pathways associated with human errors of sex determination or disorders of sex development (DSD). These new genes allow for rapid diagnosis, understanding of the pathophysiology, and prediction of future fertility. There is strong scientific evidence that sex determination requires a delicate dosage balance in the timing and levels of expression of these genes. Thus, anomalies may occur at any stage of intrauterine development. Failure of normal sex determination covers a wide spectrum of disorders, ranging from complete masculinization to true hermaphrodites (ovotesticular DSD). We hereby present a 33-year-old patient who had a small testicular size, hypergonadotropic hypogonadism, and nonobstructive azoospermia. Herein, we focus on the approaches to diagnosis and the lessons learned and review shortly the genetics of human sex determination.