Mechanisms of disease: Sex determination and differentiation

The study of patients with syndromes characterized by ambiguous genitalia and associated anomalies, together with analyses of spontaneous and engineered mutations causing similar abnormalities in animals, has elucidated many of the molecular defects causing sex reversal and disorders of reproductive function in humans. Our knowledge is expanding regarding the molecular events necessary to initiate the development of the urogenital ridge and to select and sustain further sex differentiation and development of gonads, reproductive ducts, and external genitalia. This deeper understanding has, in some cases, contributed to improved patient care both by increasing the likelihood of a positive outcome and by averting unfavorable events. This knowledge must be incorporated into treatment strategies in order to increase and sustain the function, happiness, and emotional fulfillment of patients with abnormalities of sex differentiation.