Atypical genitalia in the newborn

Ambiguous genitalia constitute a rare phenotypic presentation of the urogenital system that can signal an underlying life-threatening disorder. Thus it is imperative to determine the etiology as quickly as possible when ambiguity is noted. The formation of typical male or female external genitalia results from a number of genetic and physiological events starting with sex determination and progressing through differentiation of internal and external reproductive structures after a zygote is formed. While the inability to proceed through sex determination and differentiation in the usual manner (e.g., complete androgen insensitivity syndrome) is referred to as a disorder of sex development (DSD), not all people with DSD have ambiguous genitalia. The focus of this chapter is genital ambiguity associated with DSD in individuals who possess either a 46,XY or 46,XX chromosomal complement; however, DSD including genital ambiguity can be observed in people with other combinations of sex chromosomes such as 45,X/46,XY.