Genetics of Intersexuality

Abstract

ABSTRACT Intersexuality is not rare. In its traditional definition-the impossibility of distinguishing whether the individual is male or female-the incidence is estimated at 1/4,500 births. If all minor variants of the shape of genitalia are included in the definition of intersex, the incidence rises to close to 1%. These numbers show that, although not spoken about as openly as other conditions, intersexuality is present at a high frequency throughout the world. Understanding intersexuality from a biological perspective has been a challenge. The main cause of the slow rate of progress in this field is the tremendous genetic heterogeneity that may correspond to an intersex situation. More than a dozen medical diagnoses can be associated with the same appearance of genitalia, which taken alone may give the observer little or no clue to the pathophysiology. Dissecting the various causes of intersexuality is essential at many levels: to understand the fundamental biological events of sexual development, to better interpret long-term follow-up studies on intersex patients, and to better predict psychosexual outcome and therefore improve the clinical management of intersex patients. This paper illustrates that the biological mechanisms of intersexuality are complex, and for the most part, understanding them is still a work in progress. Despite understanding the embryology of the genitalia, the mechanisms of action of sex hormones and of a number of sex-determining genes, many intersex babies are born without a clear biological explanation. The pressing question in this field is the social issue of gender assignment and early genital surgery. The author argues that the most important criteria in assigning a gender to an intersexed newborn is the future gender identity, regardless of the chromosomal constitution, gonadal secretions, and aspect of the genitalia.