Mayer-Rokitansky-Kuster-Hauser Syndrome

What is Mayer-Rokitansky-Kuster-Hauser Syndrome?

Mayer-Rokitansky-Kuster-Hauser Syndrome syndrome (also known as Müllerian agenesis) is a genetic condition that mainly affects the female reproductive system. It causes the upper 2/3 of the vagina and uterus to be absent or underdeveloped. Women affected by this condition have a normal karyotype (46 XX) and normal secondary sexual characteristics. There are two types of Mayer-Rokitansky-Kuster-Hauser Syndrome:

• Type I – isolated absence of the proximal 2/3 of the vagina
• Type II – MURCS association (Müllerian duct aplasia, Renal dysplasia, Cervical Somite anomalies^[1]) with cardiac and auditory involvement^[2,3,4]

Anatomical malformation in MRKH syndrome.
Image source:miklosandmoore.com

This syndrome occurs in 1 of 4000-10 000 females^[5]. The severity of this syndrome might vary for each person. In most cases of Type I, the uterus and/or vagina has not developed. Rarely there might be only narrowing of the upper part of vagina and a rudimentary or underdeveloped uterus. Woman with this syndrome have fully functioning ovaries and they might be able to have children through surrogacy.

Symptoms

This syndrome usually gets diagnosed in after puberty, when a woman with normal sexual development does not start periods (primary amenorrhea). The ovary function is normal; therefore the patient might have all the bodily changes associated with menstruation, even premenstrual syndrome. Women who have underdeveloped vagina might experience abdominal pain, due to lack of passage way for menstrual blood. Other symptoms patients might experience:

• Infertility
• Difficulty having intercourse
• Urinary incontinence
• Often occurrence of urinary tract infections
• Skeletal abnormalities (Scoliosis, Klippel-Feil syndrome, face and limb malformations Holt-Oram like syndrome.)
• Hearing impairment
• Heart abnormalities

Causes

The exact causes of this syndrome are still unknown. Initially it was believed that this syndrome has a sporadic occurrence and is caused by environmental factors ^[6]. More recent research suggests that it is caused by autosomal dominant inheritance with incomplete penetrance and variable expressivity of mutated genes ^[2]. This means that the abnormal gene can be inherited from any of the parents. For dominant genetic disorders only a single copy of abnormal gene is necessary for the disease to appear. Incomplete penetrance means, that not all of individual who have this abnormal gene will be affected by this disorder. Variable expressivity is variety in occurrence and severity of the symptoms.

Diagnosis

The diagnosis of Mayer-Rokitansky-Kuster-Hauser Syndrome consists of physical examination, blood tests, imaging studies, and possibly surgery. The findings that might occur in case of Mayer-Rokitansky-Kuster-Hauser Syndrome are:

Physical examination

• Normal female sexual characteristics- developed breasts, pubic and underarm hair and fat distribution characteristic to females.
• Normal height

Gynecological examination

• Impossible or difficult to perform a speculum examination
• Outer part of genitalia are normal (labia majora and minora, clitoris)

Laboratory examination

• Chromosomal analysis to determine the karyotype and exclude other chromosomal abnormalities like Androgen Insensitivity syndrome
• Blood analysis to determine the hormone levels- luteinizing hormone, follicle stimulating hormone. These hormone levels are in normal range.

Imaging studies

• Ultrasonography– non-invasive and x-ray free method for diagnosing. It allows visualization of the involved structures. It is possible to assess the extent of vaginal and uterine obstruction or aplasia. It also possible to assess if other organs, like kidneys, bladder or fallopian tubes are involved.
• Magnetic Resonance imaging– MRI will provide the necessary information in case ultrasound has been inconclusive. It is possible to see the superficial and deep tissue and assess the organ structures. In case there is a suspicion of skeletal structure involvement, it can also be assessed.
• Computed tomography imaging– CT scan will be most helpful in visualizing the skeletal deformities.
• Intravenous pyelography– this method uses injection of intravenous dye and taking X-rays, to see how the dye is processed through the kidneys. With this method it is possible to precisely visualize the kidney and assess possible abnormalities.
• Laparoscopy as a diagnostic measure alone is rarely used. The uterine cavitation can be well assessed with MRI. Laparoscopy can be used as a diagnostic and therapeutic option in case if there are uterine remnants that cause cyclic pain ^[4].

Treatment

There is no treatment for Mayer-Rokitansky-Kuster-Hauser Syndrome, but there are measures that can be taken. The treatment is symptomatic and depends on the severity of patients symptoms. Treatment might include a variety of specialists and procedures.
First of all the patients suffering from Mayer-Rokitansky-Kuster-Hauser Syndrome should undergo counseling. Severity of this syndrome can cause severe anxiety and psychological distress, or depression.

The psychological status of the patient has to be dealt with, because the treatment might include many uncomfortable and painful procedures. There also a number of social and emotional obstacles the patients will need to face, like not being able to carry a child.

For patients who are mature enough to engage in sexual activity treatment of vaginal aplasia is suggested. Depending on the severity of aplasia, there are different surgical and non surgical approaches:

Non-surgical approach

Non-surgical approach is usually the first to be used, in order to avoid surgical intervention. This approach uses vaginal dilatators to expand or create a vagina. Plastic tubes are applied daily by a doctor or woman herself, which puts pressure to the perineum in order to create a vaginal cavity. This procedure has to be done daily and continued up to 6 months. There is a risk that woman might stretch the urethra, therefore they have to be regularly examined. This procedure requires a high compliance from the patient.

Vaginal dilatators.
Image source: http://www.vaginaldilator.co.uk/

Surgical treatment

There are a number of different approaches to create an artificial vagina- vaginoplasty. The most popular method is McIndoe technique, which uses a skin graft to create an artificial vaginal cavity. After the surgery Frank technique using the vaginal dilatators has to be applied, to avoid neovaginal stenosis. Another procedure that is often applied uses a segment of the bowel to create a neovagina ^[1].

In case of kidney involvement, recurring urinary tract infections can be treated with antibiotics.

For females with skeletal malformations reconstructive surgery and physical therapy should be used ^[4].

References

1. https://rarediseases.org/rare-diseases/mayer-rokitansky-kuster-hauser-syndrome/
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1832178/
3. https://ghr.nlm.nih.gov/condition/mayer-rokitansky-kuster-hauser-syndrome#
4. http://emedicine.medscape.com/article/953492-overview
5. http://www.acog.org/Resources-And-Publications/Committee-Opinions/Committee-on-Adolescent-Health-Care/Mullerian-Agenesis-Diagnosis-Management-and-Treatment
6. https://www.ncbi.nlm.nih.gov/pubmed/10727998