What is the most likely diagnosis for a patient with primary amenorrhea, normal secondary sexual characteristics, and normal breast development?

Primary Amenorrhea with Normal Secondary Sexual Characteristics: Müllerian Agenesis

In a patient presenting with primary amenorrhea, normal breast development, and normal secondary sexual characteristics, Müllerian agenesis (Mayer-Rokitansky-Küster-Hauser syndrome) is the most likely diagnosis. 1, 2

Diagnostic Reasoning

The presence of normal breast development is the critical distinguishing feature that narrows the differential diagnosis:

• Normal breast development requires functioning ovaries producing estrogen, which immediately excludes gonadal dysgenesis as the primary diagnosis 1, 2
• Gonadal dysgenesis causes absent or minimal secondary sexual characteristics due to ovarian failure and lack of estrogen production, presenting with elevated FSH/LH levels and no breast development 1, 2
• Pituitary failure (hypogonadotropic hypogonadism) would similarly cause absent or minimal breast development with low FSH, LH, and estradiol levels, along with delayed or absent puberty 1, 2

Why Müllerian Agenesis is Most Likely

Müllerian agenesis presents with congenital aplasia of the uterus and upper two-thirds of the vagina in women with normal secondary sexual characteristics and normal karyotype (46,XX). 3, 4

Key diagnostic features include:

• Primary amenorrhea with well-developed secondary sexual characteristics including normal breast development 5, 6
• Normal ovarian function with normal FSH, LH, and estradiol levels 2, 6
• Incidence of 1 per 4,500-5,000 females, making it the second most common cause of primary amenorrhea after gonadal dysgenesis 5, 4
• The diagnosis is typically made during adolescence when investigating primary amenorrhea 3, 4

Diagnostic Workup

The evaluation should proceed systematically:

• Pregnancy test to rule out cryptic pregnancy 2
• Pelvic examination to assess for outflow tract obstruction 2
• Pelvic ultrasound to evaluate uterine presence and anatomy, which will reveal absent or rudimentary uterus 2, 6
• Magnetic resonance imaging (MRI) is the gold standard for confirming the diagnosis and detecting associated anomalies 6, 3
• Laboratory evaluation including FSH, LH, estradiol, and testosterone should show normal/low-normal levels consistent with normal ovarian function 2, 6

Associated Anomalies

Müllerian agenesis is classified as Type I (isolated) or Type II (with extragenital manifestations). 3

Type II patients may have:

• Renal anomalies (unilateral renal agenesis, ectopic kidney) 6, 7
• Skeletal abnormalities 3
• Cardiac malformations 3
• Ear anomalies 3

Critical Pitfall to Avoid

Do not assume functional hypothalamic amenorrhea or PCOS in primary amenorrhea with normal breast development without first ruling out anatomic causes through imaging. 2 The presence of normal secondary sexual characteristics can falsely reassure clinicians, leading to delayed diagnosis of structural abnormalities.

Why Other Options Are Incorrect

• Vaginal agenesis alone (Option C) is essentially the same entity as Müllerian agenesis, as the syndrome involves both uterine and vaginal aplasia 4
• Pituitary failure (Option A) would present with absent breast development and delayed puberty 1, 2
• Gonadal dysgenesis (Option D) would present with absent secondary sexual characteristics and elevated FSH/LH due to ovarian failure 1, 2