Mayer–Rokitansky–Küster–Hauser syndrome

Overview

Mayer–Rokitansky–Küster–Hauser syndrome (MRKH syndrome) is a rare congenital disorder characterized by the underdevelopment or complete absence of the uterus and upper part of the vagina in individuals with a normal female karyotype (46,XX) and typical external female genitalia. Despite these anomalies, individuals with MRKH have normal ovarian function, normal secondary sexual characteristics, and typical female hormone levels.

MRKH syndrome affects approximately 1 in 4,500 to 5,000 female births and is usually discovered during adolescence when menstruation fails to start (primary amenorrhea). The condition can be classified into two types: Type I (isolated MRKH) and Type II (MRKH with associated renal, skeletal, and sometimes auditory or cardiac anomalies).

Causes

The exact cause of MRKH syndrome is not fully understood, but it is believed to result from disrupted embryonic development of the Müllerian ducts during the first few weeks of fetal growth. The Müllerian ducts normally develop into the uterus, fallopian tubes, cervix, and upper vagina.

Several factors may contribute to this disruption:

• Genetic factors: While most cases are sporadic, familial occurrences suggest a possible genetic basis. Mutations in genes involved in reproductive tract development (e.g., WNT4, LHX1, HNF1B) have been studied, though a single consistent gene mutation has not been identified in all patients.

• Environmental influences: Possible in utero exposure to teratogens or endocrine disruptors may interfere with normal reproductive tract development, although no definitive link has been established.

MRKH is not associated with chromosomal abnormalities; individuals have a normal female 46,XX karyotype.

Symptoms

The primary clinical feature of MRKH syndrome is the absence of menstruation (primary amenorrhea) despite normal development of breasts and pubic hair. Other symptoms and signs include:

• Primary amenorrhea: Most individuals are diagnosed during their teenage years when they do not begin menstruating by age 15 or 16.

• Normal external genitalia and secondary sexual characteristics: Breast development, pubic hair, and external vaginal appearance are normal.

• Shortened or absent vaginal canal: The upper portion of the vagina may be underdeveloped or missing, which may lead to difficulty with sexual intercourse.

• Associated anomalies (in Type II MRKH):

  • Renal anomalies (e.g., unilateral renal agenesis, ectopic kidneys, horseshoe kidney)

  • Skeletal abnormalities (e.g., scoliosis, vertebral fusion)

  • Auditory defects (hearing loss in some cases)

  • Cardiac anomalies (rare)

Ovarian function remains normal, allowing for typical hormone production and the possibility of biological motherhood via assisted reproductive technologies with a gestational carrier.

Diagnosis

Diagnosis of MRKH syndrome typically begins with the evaluation of primary amenorrhea in adolescent girls who show normal signs of puberty. Diagnostic steps include:

• Clinical examination: Assessment of external genitalia, breast development, and pelvic anatomy.

• Pelvic ultrasound: Often the first imaging modality used to assess the presence of the uterus and vagina. Ovaries are usually present and appear normal.

• Magnetic Resonance Imaging (MRI): Provides detailed imaging of the internal reproductive structures and helps confirm the absence or underdevelopment of the uterus and vagina. Also used to detect associated renal or skeletal anomalies.

• Karyotype analysis: Confirms a normal female chromosomal pattern (46,XX) and rules out disorders of sexual development (e.g., androgen insensitivity syndrome).

• Hormonal testing: Estrogen, LH, FSH, and testosterone levels are typically within normal female ranges.

• Renal and skeletal imaging: Recommended to evaluate for associated anomalies, especially in suspected Type II MRKH.

Early diagnosis allows for proper psychological counseling, reproductive planning, and management of any associated anomalies.

Treatment

Treatment for MRKH syndrome focuses on creating a functional vaginal canal (if desired for sexual activity), managing associated anomalies, and providing psychological support. Management options include:

• Non-surgical vaginal dilation (first-line approach):

  • Use of progressive vaginal dilators to gradually stretch and lengthen the vaginal canal

  • Highly effective and minimally invasive

  • Requires commitment and guidance from a trained provider

• Surgical vaginoplasty (for those who fail dilation or prefer surgery):

  • McIndoe procedure: Uses skin grafts to create a neovagina

  • Vecchietti procedure: Laparoscopic method to elongate the vaginal dimple

  • Sigmoid colon vaginoplasty: Uses a segment of the bowel to create a vaginal canal

• Fertility support:

  • Ovaries are functional, so biological motherhood is possible using assisted reproductive technologies such as IVF with a gestational carrier (surrogate)

• Management of associated anomalies:

  • Referral to nephrology, orthopedics, or ENT specialists as needed

• Psychological counseling:

  • Support for emotional and sexual well-being

  • Assistance with identity and relationship concerns

Treatment should be individualized based on the patient’s goals, age, and physical and emotional needs.

Prognosis

The long-term prognosis for individuals with MRKH syndrome is generally excellent with appropriate medical and psychological support. Key aspects of the prognosis include:

• Normal life expectancy: MRKH does not affect life span.

• Normal sexual function: Most individuals can achieve satisfactory sexual activity following vaginal dilation or surgical neovagina creation.

• Fertility potential: While natural conception is not possible due to absent uterus, individuals can have genetically related children via IVF and surrogacy.

• Emotional adjustment: Supportive counseling improves coping and adaptation, particularly during adolescence and young adulthood.

With increased awareness and patient advocacy, individuals with MRKH can lead fulfilling lives, with access to supportive communities, medical advancements, and reproductive options.