Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a rare condition in which a girl is born without a complete uterus and/or vagina. This syndrome is typically first recognized when a girl does not start having periods by age 15 or 16. Other signs may include not being able to have vaginal intercourse and get pregnant, and occasionally problems with the kidneys, spine, hearing, or heart.

MRKH syndrome affects about 1 in every 4,500 to 5,000 girls and women. It is one of the most common reasons for not starting periods, second only to underdeveloped ovaries. As the genitals look normal on the outside, MRKH syndrome is often found when periods do not start during the teenage years. Most cases happen by chance, but sometimes MRKH syndrome runs in families.

MRKH syndrome can be hard both physically and emotionally, but there are treatments and ways to help. With medical care and support, many people with MRKH syndrome can live healthy and fulfilling lives.

“MRKH is a serious health condition that carries multiple health implications with one of them being unable to carry a pregnancy or have vaginal intercourse, which has profound physical and mental health implications,” says Alla Vash-Margita, MD, a Yale Medicine specialist in pediatric and adolescent gynecology. ”However, patients with MRKH have an excellent prognosis if they receive appropriate care by a team of physicians skilled in delivering such care.”

”As a great example of the individualized approaches at Yale, our team is able to offer multiple modalities for creation of a neovagina based on shared decision making,” says Dr. Vash-Margita.

Before birth, a girl’s reproductive system starts to form from two small tubes called müllerian ducts. Around the fifth or sixth week of pregnancy, these ducts begin to grow and unite. They turn into the fallopian tubes, uterus, cervix, and most of the vagina. In MRKH syndrome, because these ducts do not form completely or are missing, the uterus and the vagina are either very small or not present.

Individuals with MRKH syndrome have normal chromosomes, look normal on the outside, and have normal ovaries. Because the ovaries produce hormones normally, they go through normal body changes during puberty. They develop normal breasts and pubic hair like everybody else, but, because the uterus and vagina are largely not fully formed, they do not have periods and cannot carry a pregnancy. Absence of a normal-length vagina may not allow comfortable vaginal intercourse.

MRKH syndrome is present at birth, but it is often not noticed until the teenage years or adulthood, when periods do not start. The condition can be mild or more severe. In some people, only the reproductive organs are affected (type I). In others (type II), there can also be problems with the kidneys, bones, heart, or hearing, including the following:

1. They may have only one kidney, or kidneys may be smaller, joined together, and not located in their usual places
2. Spinal and vertebral anomalies may occur
3. Abnormal ear shape and/or canal may affect hearing
4. Heart anomalies from birth

In rare cases, people with type II MRKH syndrome have differences in their hands, arms, or feet, such as webbed fingers or toes, a missing bone in the forearm, or missing fingers or toes. There may also be differences in the face, such as a split lip or palate, or one side of the face looking different from the other.

Doctors do not know exactly what causes MRKH syndrome. It is likely that genes and maybe other factors play a part, but no single cause has been found. Most cases happen in people with no family history, but sometimes MRKH syndrome is seen in families, which suggests genes may be involved.

Some changes in certain genes and parts of chromosomes have been found in a few people with MRKH syndrome. These genes help the reproductive system develop before birth. Changes in these genes or chromosomes have only been found in a small number of people, and it is not always clear if they are the reason for MRKH syndrome.

In the past, some doctors thought that things like medicines or illnesses during pregnancy might cause MRKH syndrome, but studies have not shown a clear link. Right now, MRKH syndrome is thought to happen because of a mix of genetic and other factors that affect how the müllerian ducts develop.

Risk factors for MRKH syndrome include:

• Family history of MRKH syndrome or similar reproductive problems
• Changes in certain genes
• Certain changes in chromosomes

Symptoms of MRKH syndrome may include:

• Not starting periods
• Not being able to carry a pregnancy
• Inability to have vaginal intercourse or pain with vaginal intercourse

People with type II MRKH syndrome may have other symptoms because of problems in other parts of the body. These can include:

• Curved spine (scoliosis)
• Hearing loss or hearing problems
• Webbed fingers or toes
• Short neck
• Neck that does not move well
• Shoulder blades that are higher than normal
• Split lip or palate
• Face that is not symmetrical
• Shortness of breath, tiredness, heart murmur, or other signs of heart problems
• Frequent urinary tract infections

To diagnose MRKH syndrome, your doctor reviews your medical history, conducts a physical exam, and orders several diagnostic tests.

The doctor may ask about your symptoms, such as missing periods, any pain or trouble during sex, and whether anyone in the family has MRKH syndrome or kidney problems. During the physical exam, the doctor will check for normal puberty changes, look at the outside genitals, and may look for signs of bone or limb differences.

Tests that help diagnose MRKH syndrome include:

• Ultrasound: It is often the first test that shows the inside organs such as the uterus, the ovaries, tubes, and the vagina, as well as the kidneys.
• Magnetic resonance imaging (MRI): This test can provide even more detailed images of the reproductive organs, kidney, and bones.
• Karyotyping: This test looks for the chromosomal structure of an individual. There are conditions with abnormal chromosomes which may also cause incomplete genital development. This test makes sure they have normal (46,XX) chromosomes and rules out the other conditions.
• X-ray of the spine: This may be done to look for bone problems, especially if there are symptoms.
• Hearing test (audiometry): If there are signs of hearing loss, a hearing test may be done.
• Echocardiogram: If heart problems are suspected, this test shows the shape of the heart.

Blood tests to check hormone levels (prolactin, thyroid stimulating hormone (TSH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol) are usually normal in MRKH syndrome and can help rule out other reasons for missing periods.

Many problems of a patient with MRKH syndrome may be improved or resolved. Treatment is different for each person and may involve several types of doctors.

Treatments for MRKH syndrome include:

• Counseling and support: Learning you have MRKH syndrome can be hard emotionally. Talking with a counselor or joining a support group can help you and your family cope.
• Creating a vagina: For those who want to have vaginal sex, treatment can help make a working vagina. This can be done by:
• Nonsurgical vaginal dilation: The first choice is to use special dilators to gently stretch and lengthen the vagina. If this works, there will be no need for surgery.
• Surgical vaginoplasty: If dilation does not work or is not wanted, surgery can create a vagina using different methods. After surgery, using dilators or having regular sex is usually needed to keep the vagina open and working.
• Treating other problems: If MRKH syndrome comes with kidney, bone, hearing, or heart problems, treatment may include medicine, surgery, or other therapies for those issues.
• Fertility options: Women with MRKH syndrome cannot carry a pregnancy because they do not have a working uterus. Options for having biological children include in vitro fertilization (IVF) with a surrogate or, in some cases, uterus transplant. Also, individuals with MRKH syndrome can choose to adopt a child.
• Pain management: If a small, underdeveloped fragment of uterus causes pain, surgery may be needed to remove it. Pain can also be treated with medicine or hormone therapy.

People with MRKH syndrome may have certain complications, including:

• Not being able to have vaginal intercourse
• Not being able to carry a pregnancy
• Emotional distress, such as anxiety, depression, or trouble with self-esteem and identity
• Pain or trouble during sex because the vagina is short or missing, which may need treatment
• Problems after surgery to create a vagina, which can affect nearby organs or the new vagina
• Endometriosis, a painful condition that can happen if a small, underdeveloped fragment of uterus has working lining
• Problems with other organ systems, including the kidneys, spine, other bones, ears, and heart.

With good medical care, most people can manage the physical symptoms of MRKH syndrome. They may see gynecologists, kidney specialists, orthopaedic surgeons, cardiologists, or other specialists to help with their health.

Emotional and psychological support is important, because MRKH syndrome can affect self-esteem, relationships, and mental health.

While not being able to carry a pregnancy is a lifelong challenge, options like IVF with a surrogate or, in some cases, uterus transplant may help some people have biological children.

“Providers at Yale are uniquely positioned to provide interdisciplinary, individualized care for females with MRKH syndrome,” says Dr. Vash-Margita. “Our team consists of the reproductive health specialists working closely with the mental health providers, radiologists, and nurses. We provide care to individuals with MRKH syndrome across the lifespan including the youngest patients. In addition to clinical care, our team is offering whole genome sequencing to trios (a person with MRKH and biologic mom and dad) in search of genetic causes of this condition.”