A 19-year-old woman presents with primary amenorrhea, absent axillary and pubic hair, normal female phenotype, and blind-ending vagina. Serum testosterone is in the male range. The karyotype is 46,XY. What is the underlying molecular defect?
- A Deletion of SRY gene on Y chromosome — Swyer syndrome (pure gonadal dysgenesis)
- B 5α-reductase type 2 deficiency — incomplete virilisation at puberty
- C Loss-of-function mutation in the androgen receptor (AR) gene — complete androgen insensitivity syndrome (CAIS) ✓
- D 17α-hydroxylase deficiency — absent sex hormone synthesis with hypertension
Explanation
The clinical picture — 46,XY karyotype, absent pubic/axillary hair (due to androgen insensitivity), normal female external phenotype, blind-ending vagina (müllerian structures absent due to AMH from testes), and male-range testosterone — is diagnostic of Complete Androgen Insensitivity Syndrome (CAIS). A loss-of-function mutation in the X-linked AR gene prevents androgen receptor signalling; therefore testosterone cannot cause virilisation or pubic/axillary hair growth. In Swyer syndrome, gonads are dysgenetic streaks with very low testosterone. In 5α-reductase deficiency, patients virilise at puberty. In 17α-hydroxylase deficiency, no sex steroids are made and hypertension is present.
Reference: Shaw's Textbook of Gynaecology, 17th ed.
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