Sexual Ambiguity

Introduction

• Description: Structural abnormalities present at birth may make the assigning of an appropriate sex of rearing (gender) difficult or impossible (sexual ambiguity). The evaluation of these infants represents both a social and medical emergency because causative life-threatening conditions may be present.

• Prevalence: Less than 1/2000 births.

• Predominant Age: Present at birth.

• Genetics: Some enzymatic defects may be inheritable. A history of a previously affected relative may be present for patients with androgen insensitivity or its variants.

Etiology and Pathogenesis

• Causes: Enzyme defects (5α-reductase, 11β- 17α-, or 21-hydroxylase deficiencies [95%]), androgen insensitivity syndrome, intrauterine androgen exposure. Most patients with ambiguous genitalia prove to be androgenized females with adrenal hyperplasia. The enzyme defects present in these individuals cause the adrenal glands to produce abnormally high levels of virilizing hormones. Cases are often placed into one of four categories: female pseudohermaphroditism, male pseudohermaphroditism, dysgenetic gonads (including true hermaphroditism), and true hermaphroditism (rare). Some have advocated replacing these designations with the less pejorative overarching term disorders (or difference) of sexual development (DSD). The second most common cause of atypical genital appearance is 45,X/46,XY mosaicism.

• Risk Factors: In utero androgen exposure. (Along with clitoral enlargement, some degree of fusion of the urogenital folds can occur with significant androgen exposure from the 8th–12th week of gestation. This can manifest as ambiguous genitalia at birth. If exposure occurs after the 12th gestational week, only clitoral enlargement occurs. Females with only clitoral enlargement mature normally and have normal fertility, and there is almost total regression of the clitoromegaly.)

Signs and Symptoms

• Incompletely formed or malformed external genitalia (varies from labial adhesion to clitoral hypertrophy and vaginal agenesis based on cause and genetic makeup of the individual)

• Infants—rapid development of vomiting, diarrhea, dehydration, and shock (congenital adrenal hyperplasia)

Diagnostic Approach