A 17-year-old with primary amenorrhoea has a 46,XY karyotype, normal female external genitalia, absent uterus, and absent axillary/pubic hair. Serum testosterone is in the male normal range. Serum oestradiol is low-normal. What is the molecular mechanism underlying this condition?
- A Loss-of-function mutation in SRY gene preventing testicular development
- B Absent androgen receptor (AR) function causing complete androgen insensitivity — end-organs cannot respond to testosterone or DHT ✓
- C 5α-reductase deficiency — inability to convert testosterone to DHT, preventing external virilisation
- D 17α-hydroxylase deficiency causing inadequate sex steroid synthesis with cortisol deficiency
Explanation
Complete androgen insensitivity syndrome (CAIS) results from loss-of-function mutations in the androgen receptor (AR) gene on chromosome Xq11-12. Testes produce testosterone and AMH normally — AMH causes Müllerian duct regression (absent uterus, absent upper vagina). Testosterone cannot act (absent/dysfunctional AR), so Wolffian duct structures regress and female external genitalia develop by default. Peripheral aromatisation of testosterone to oestrogen explains breast development and low-normal oestradiol. Sparse pubic/axillary hair is due to absent androgen action on hair follicles. 5α-reductase deficiency also has XY karyotype and male testosterone but external genitalia are ambiguous/partially masculinised at birth, and virilisation occurs at puberty — distinct from CAIS.
Reference: Shaw's Textbook of Gynaecology, 17th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.