Patients with
ambiguous genitalia stand a far better chance of receiving a rapid diagnosis, appropriate replacement
therapy, and functional surgical reconstruction than was the case even a decade ago. Although the etiologies of
true hermaphroditism and
mixed gonadal dysgenesis remain elusive, most gene defects in
female pseudohermaphroditism or CAH have been pinpointed to the
21-hydroxylase gene. Incomplete masculinization has been found to be due to defects in the
androgen receptor,
5 alpha-reductase, or
enzymes in the pathway from
cholesterol to
testosterone. SRY point mutations have been implicated in 46XY pure
gonadal dysgenesis. Retained müllerian ducts have been attributed to point mutations in the MIS gene; those with normal MIS levels should be expected to have receptor deficits. In utero diagnoses and treatment and diagnosis at the preimplantation stage may prove to be very important for the care of some of these patients, who may be potential candidates for gene replacement
therapy. When necessary, surgical reconstruction can be done. If the child is to be raised as a female, clitoral recession, labioscrotal reductions and advancements, and vaginoplasties for exteriorization can be accomplished in early infancy as an extensive one-stage procedure. If patients are to be raised as males, then various types of
hypospadias repair can be done, gonads can be replaced with
prostheses, the
prepenile scrotum can be reconstructed, and müllerian structures can be removed with the goal of preserving the vas deferens. Replacement
therapy with
glucocorticoids and
mineralocorticoids must be precisely managed to permit proper growth, and
testosterone,
estrogen, and
progesterone replacement must be carefully considered and managed. A most important
element in the care of these patients is the psychological support that first the families and then the patient require. This must be delivered with sensitivity. The proper care of these complex patients requires that the physician be a scientist as well as a clinician and a skilled technician.