A 25-year-old woman presents with primary amenorrhea. Examination shows female external genitalia, normal breast development (Tanner stage 5), absent axillary and pubic hair, and a short vagina ending blindly. Karyotype is 46,XY. LH is elevated, testosterone is in the normal male range. MRI shows no uterus, no ovaries, but bilateral inguinal testes. What is the diagnosis, and what is the underlying molecular defect?
- A Complete androgen insensitivity syndrome (CAIS) due to loss-of-function mutation in the androgen receptor (AR) gene on Xq11-12 ✓
- B 5-alpha-reductase deficiency due to mutation in SRD5A2 gene
- C Swyer syndrome (46,XY complete gonadal dysgenesis) due to SRY gene deletion
- D Partial androgen insensitivity syndrome (PAIS) due to missense AR mutation
Explanation
This is a classic presentation of complete androgen insensitivity syndrome (CAIS), formerly called testicular feminization syndrome. The molecular basis is loss-of-function mutations in the androgen receptor (AR) gene located on Xq11-12 (X-linked). Despite 46,XY karyotype, testosterone and DHT cannot signal through a dysfunctional AR, so male-pattern differentiation does not occur. MIS/AMH from testes causes Müllerian regression (no uterus, upper vagina); without androgen signaling, Wolffian ducts regress (no vas deferens), and female external genitalia develop by default. Breast development occurs because testosterone is aromatized to estrogen peripherally, but no pubic/axillary hair develops (hair follicles are androgen-dependent). Management includes gonadectomy after puberty (malignancy risk ~2–5% if testes retained), followed by estrogen replacement.
Reference: Shaw's Textbook of Gynaecology, 17th ed.
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Written and medically reviewed by the StethoPrep medical team.