A 19-year-old patient presents to your office with primary amenorrhea. She has normal breast and pubic hair development, but the uterus and vagina are absent. Diagnostic possibilities include

Since this patient has other signs of pubertal development which are sex steroid-dependent, we can conclude some ovarian function is present. This excludes such conditions as gonadal dysgenesis and hypothalamic-pituitary failure as possible causes of her primary amenorrhea. Mullerian defects are the only plausible cause, and the diagnostic evaluation in this patient would be directed toward both confirmation of this diagnosis and establishment of the exact nature of the Mullerian defect. Mullerian agenesis, also known as Mayer-Rokitansky-Kuster-Hauser syndrome, presents as amenorrhea with absence of a vagina. The incidence is approximately 1 in 10,000 female births. The karyotype is 46, XX. There is normal development of breasts, sexual hair, ovaries, tubes, and external genitalia. There are associated skeletal (12%) and urinary tract (33%) anomalies. Treatment generally consists of progressive vaginal dilation or creation of an artificial vagina with split-thickness skin grafts (Mclndoe procedure). Testicular feminization, or congenital androgen insensitivity syndrome, is an X-linked recessive disorder with a karyotype of 46, XY. These genetic males have a defective androgen receptor and/or downstream signal transduction mechanism (in the genome) such that the androgenic signal does not have its normal tissue-specific effects. This accounts for 10% of all cases of primary amenorrhea. The patient presents with an absent uterus and blind vaginal canal. However, in these patients the amount of sexual hair is significantly decreased. Although there is a 25% incidence of malignant tumors in these patients, gonadectomy should be deferred until after full development is obtained. In other patients with a Y chromosome, gonadectomy should be performed as early as possible to prevent masculinization. Patients with gonadal dysgenesis present with lack of secondary sexual characteristics. Patients with Klinefelter syndrome typically have a karyotype of 47, XXY and a male phenotype. Causes of primary amenorrhea, in descending order of frequency, are gonadal dysgenesis, Mullerian agenesis, and testicular feminization. XYY syndrome and Turner syndrome often present with menstrual difficulties, but these patients have a uterus.