Müllerian Agenesis

Müllerian Agenesis

Müllerian agenesis is a disorder that occurs in females and mainly affects the reproductive system. It occurs in 1 out of every 4,000–10,000 females. The most common presentation of müllerian agenesis is congenital absence of the vagina, uterus, or both, which also is referred to as müllerian aplasia, Mayer–Rokitansky–Küster–Hauser syndrome, or vaginal agenesis.

Müllerian agenesis is caused by embryologic growth failure of the müllerian duct, with resultant agenesis or underdevelopment of the vagina, uterus, or both. Also;

  • The vaginal canal is absent or markedly shortened.
  • A single midline uterine remnant may be present or uterine horns (with or without an endometrial cavity) can exist.
    • Most patients have small rudimentary müllerian bulbs without any endometrial activity.
    • In 2–7% of patients with müllerian agenesis, active endometrium is found in these uterine structures. These patients will present with cyclic or chronic abdominal pain.
  • The ovaries, given their separate embryologic source, are normal in structure and function.
  • They also have normal female external genitalia and normal breast and pubic hair development, thus showing normal development of secondary sexual characteristics.
  • Women have a female chromosome pattern (46,XX karyotype).

Presentation:

Often, the first noticeable sign of müllerian agenesis is that menstruation does not begin by age 16 (primary amenorrhea), with normal growth and development. On physical examination, patients with müllerian agenesis have normal height, secondary sexual characteristics, body hair, and external genitalia. Furthermore, a vagina is either absent or present as a short blind-ended structure without a cervix at the vaginal apex. Patients with müllerian agenesis have a normal 46,XX karyotype and a normal hormonal profile.

Differential Diagnosis:

Differential diagnosis of Müllerian aplasia includes patients presenting with primary amenorrhea and with normal secondary sexual characteristics. This should first lead to exclusion of gonadal dysgenesis.

The differential diagnosis of müllerian agenesis includes congenital absence of the vagina (with or without uterine structures), a low transverse vaginal septum, an imperforate hymen, as well as 46,XY disorders of sex development, including androgen insensitivity and 17α-hydroxylase deficiency.

Evaluation:

  • Ultrasonography and Magnetic Resonance Imaging: Conventional transabdominal, translabial, or transrectal ultrasonography; three-dimensional ultrasonography; and magnetic resonance imaging can be used to evaluate the müllerian structures and are helpful in definitively characterizing anatomy.
    • Magnetic resonance imaging has been suggested to assess the reproductive anatomy, although it rarely is needed in the initial evaluation unless ultrasound evaluation for the presence of functional endometrium in a müllerian structure is equivocal.
    • Evaluation for associated congenital, renal, or other anomalies is essential because up to 53% of patients with müllerian agenesis have concomitant congenital malformations, especially of the abdominal wall, urinary tract, and skeleton. Ultrasonography can be used to screen for the more common findings of renal agenesis or a pelvic kidney.
  • Laparoscopy: Although laparoscopy is not necessary to diagnose müllerian agenesis, it may be useful in the treatment of patients with functional rudimentary uterine horns. Laparoscopy is seldom required to make the diagnosis but may be appropriate in the patient presenting with pelvic pain. When obstructed hemi-uteri are identified (uterine horns with the presence of active endometrium without an associated cervix and upper vagina), then laparoscopic removal of the unilateral or bilateral obstructed uterine structures should be performed. Endometriosis can develop from retrograde menstruation from the obstructed uterine horn, which presents as dysmenorrhea and pelvic pain. In most cases, surgical excision of the uterine horn results in resolution of the endometriosis.

Other Associated Malformations with Müllerian Agenesis/Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome:

MRKH may be isolated (type I) but it is more frequently associated with renal, vertebral, and, to a lesser extent, auditory and cardiac defects (MRKH type II or MURCS association). Other associated malformations include digital anomalies (syndactyly, polydactyly). Scoliosis is the most common skeletal abnormality associated with müllerian agenesis. It also should be noted that there is an increased, but small, rate of hearing impairment in patients with müllerian agenesis. A variety of uterine anomalies, including müllerian agenesis, can be seen in association with other anomalies and syndromes, such as VATER/VACTERL and anorectal malformations.

Once MRKH syndrome is diagnosed, a full check-up must be undertaken to search for associated malformations. Moreover, when diagnosing an MRKH syndrome in a patient, it is important to consider the family history. Depending on the background, investigation of the patient’s relatives may also be recommended, mainly for renal but also for skeletal malformations.

Management:

Young women diagnosed with MRKH syndrome suffer from extreme anxiety and very high psychological distress when they are told they have no uterus and vagina. Management of patients with müllerian agenesis includes psychosocial counseling to address the functional and emotional effects of genital anomalies as well as correction of the anatomical defect. Patients should be given a brief, written medical summary of their condition, including a summary of potential concomitant malformations. This information may be useful if the patient requires urgent medical care or emergency surgery from a health care provider unfamiliar with müllerian agenesis.

  • Psychosocial Counselling:

The most important steps in the effective management of müllerian agenesis are correct diagnosis of the underlying condition, evaluation for associated congenital anomalies, and psychosocial counselling to address the functional and emotional effects of genital anomalies before any treatment or intervention. As psychological distress is very important in young women with müllerian agenesis, it is essential for the patients and their families to attend counselling before and throughout treatment.

The best predictor of good emotional outcome after diagnosis and vaginal creation is a good relationship between the patient and her parent(s) or guardian(s) and the ability to share feelings with family and friends. Contact with a support group of young women with the same diagnosis may be helpful. Referral to a mental health professional for ongoing support is worthwhile for some patients.

  • Correction of the vaginal aplasia (creating neovagina):

Timing for nonsurgical or surgical creation of a neovagina is elective; however, it is best planned when the patient is emotionally mature and expresses the desire for correction. Nonsurgical creation of the vagina is the appropriate first-line approach in most patients. In cases in which surgical intervention is required, referrals to centers with expertise in this area should be considered because few surgeons have extensive experience in construction of the neovagina.


Questions


What genes are related to Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome?

The cause of MRKH syndrome is unknown, although it probably results from a combination of genetic and environmental factors. Researchers have not identified any genes associated with MRKH syndrome.

The reproductive abnormalities of MRKH syndrome are due to incomplete development of the Müllerian duct. This structure in the embryo develops into the uterus, fallopian tubes, cervix, and the upper part of the vagina. The cause of the abnormal development of the Müllerian duct in affected individuals is unknown. Originally, researchers believed that MRKH syndrome was caused by something the fetus was exposed to during pregnancy, such as a medication or maternal illness. However, studies have not identified an association with maternal drug use, illness, or other factors. It is also unclear why some affected individuals have abnormalities in parts of the body other than the reproductive system.

How do people inherit Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome?

Most cases of MRKH syndrome occur in people with no history of the disorder in their family.

Less often, MRKH syndrome is passed through generations in families. Its inheritance pattern is usually unclear because the signs and symptoms of the condition frequently vary among affected individuals in the same family. However, in some families, the condition appears to have an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means that one copy of the altered gene in each cell is typically sufficient to cause the disorder, although no genes have been associated with MRKH syndrome.