General Medical Information

Agonadia (Testicular Regression Syndrome)

Joe Leigh Simpson

In agonadia, gonads are absent, external genitalia are normal, and all but rudimentary müllerian or wolffian derivatives are absent. External genitalia usually consist of a phallus about the size of a clitoris, underdeveloped labia majora, and nearly complete labioscrotal fusion. Persistent urogenital sinus often is present. By definition, gonads are undetectable. Neither normal müllerian derivatives nor normal wolffian derivatives ordinarily are present; however, rudimentary structures may be present along the lateral pelvic wall. Somatic anomalies (craniofacial or vertebral anomalies or mental retardation) may coexist.

The pathogenesis of agonadia must take into account not only absence of gonads but also abnormal external genitalia and absence of internal ducts. Two explanations seem plausible:

1. Fetal testes functioned long enough during development to inhibit müllerian development but not long enough to allow complete normal male sexual differentiation. Believing this explanation to be valid, some prefer the appellation testicular regression syndrome.

2. Alternatively, gonadal, ductal, and genital systems all could have developed abnormally as a result of either defective primordium, defective connective tissue, or teratogenic action. Coexistence of somatic anomalies is most consistent with this second hypothesis.

Several sibships of affected males have been reported. SRY is present, indicating that pathogenesis does not involve gross perturbation of that gene. Kwok found no mutations in the sequence 2-kb 5′ to the SRY coding region.