Normal sexual development requires a series of sequential and highly regulated events early in fetal development. This sexual differentiation process is regulated through complex interactions from both genetic and hormonal signals. Any disruption in this developmental pathway can lead to a disorder of sex differentiation (DSD).
Neonates born with ambiguous genitalia present a daunting challenge to all involved in health care delivery to the individual patient. An urgent evaluation by appropriate disciplines with discrete and delicate interaction with the family is mandatory. Older and potentially negative and confusing terminology has been replaced and should not be used. A new nomenclature for disorders of sex development, introduced at the 2005 Chicago Consensus Conference,1 is more precise, integrates better the progress in our understanding of the molecular basis of development, and is more sensitive to the concerns of the family and patients (Table 48-1).
Table 48-1Proposed Revised Nomenclature ||Download (.pdf) Table 48-1 Proposed Revised Nomenclature
|Previous ||Proposed |
|Intersex ||Disorders of sex development (DSD) |
|Male pseudohermaphrodite || |
| Undervirilization of an XY male ||46,XY DSD |
| Undermasculinization of an XY male || |
|Female pseudohermaphrodite || |
| Overvirilization of an XX female ||46,XX DSD |
|Masculinization of an XX female || |
| True hermaphrodite ||Ovotesticular DSD |
|XX male or XX sex reversal ||46,XX testicular DSD |
|XY sex reversal ||46,XY complete gonadal dysgenesis |
NORMAL SEXUAL DIFFERENTIATION AND DEVELOPMENT
Undifferentiated Stage of Sexual Differentiation
Normal fetal development of the gonads and the genitalia proceed through 3 sequential stages. The first stage involves the formation of the bipotential gonads from the adrenogonadal ridge at approximately 4 to 5 weeks’ gestation. During this undifferentiated stage, identical structures form in both the XY and XX embryo (Figure 48-1). These structures emanate from the mesonephros and coelomic epithelium. They are the wolffian (precursors to the formation of the seminal vesicles, epididymis, and vas deferens) and müllerian ducts (precursors to the fallopian tubes, uterus, and vagina).
Diagram of the external genitalia in the undifferentiated period. (Reproduced with permission from Diamond.29)
During this phase, the cloaca, which is the terminal portion of the hindgut limited by the cloacal membrane, is partitioned into an anterior urogenital sinus and a posterior anorectal canal. Subsequently, the urogenital sinus becomes the bladder in both sexes and is the precursor for the prostate and proximal urethra in males and the entire urethra and vagina in females.
By the seventh week of gestation, the undifferentiated gonads in a male embryo develop into a testis under the influence of the SRY (sex determining region of ...