Review Question - QID 214516

This patient who presents with primary amenorrhea and is found to have a vagina that ends in a blind pouch with an otherwise normal exam most likely has Mullerian agenesis, which is caused by degeneration of the paramesonephric duct.

Mullerian agenesis is the most common cause of primary amenorrhea among patients with a normal 46,XX karyotype. Mullerian agenesis is caused by degeneration of the paramesonephric duct resulting in congenital absence of a uterus and the upper portion of the vagina. Other than the absence of a uterus, patients develop with phenotypically normal secondary sexual characteristics and undergo thelarche and adrenarche normally. Physical exam will reveal a vagina that ends in a blind pouch, and ultrasound will show normal ovaries but an absent uterus. Patients often require surgical modification of the vagina to allow for sexual intercourse.

Incorrect Answers:
Answer 1: 5-alpha reductase enzyme deficiency will present with normal internal gonads but ambiguous external genitalia in 46,XY males. During puberty, elevated testosterone levels lead to masculinization and often require gender assignment by the parents who may have been raised as biological females. Surgical fixation of cryptorchidism is required to decrease the risk of testicular cancer.

Answer 2: 21-alpha-hydroxylase enzyme deficiency is the most common cause of congenital adrenal hyperplasia and will present with precocious puberty in both sexes. Additionally, this mutation leads to mineralocorticoid and cortisol deficiencies that result in hyponatremic hypotension and diffuse skin pigmentation, respectively.

Answer 3: Chromosomal number abnormality can cause infertility in patients with Turner syndrome (45,XO). These patients will present with cystic hygroma, shield chest, webbed neck, and streak ovaries.

Answer 4: Insensitivity of the testosterone receptor, also known as testicular feminization, presents as a normal appearing female with a male genotype. Patients with this disease will have a rudimentary vagina due to production of Mullerian inhibitory factor, cryptorchid testes, and no sexual hair development. In contrast to Mullerian agenesis, these patients will have no ovaries and cryptorchid testes that are often found in the inguinal canal.

Bullet Summary:
Mullerian agenesis presents with primary amenorrhea and congenital absence of the uterus in an otherwise phenotypically normal 46,XX female.