Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a disorder that mainly affects the female reproductive system. This condition causes the vagina and uterus to be underdeveloped or absent, although external genitalia are normal. Affected individuals usually do not have menstrual periods due to the absence of a uterus. Often, the first noticeable sign of MRKH syndrome is that menstruation does not begin by age 16 (primary amenorrhea). People with MRKH syndrome have a female chromosome pattern (46,XX) and normally functioning ovaries. They also have normal breast and pubic hair development. Although people with this condition are usually unable to carry a pregnancy, they may be able to have children through assisted reproduction.

When only reproductive organs are affected, the condition is classified as MRKH syndrome type 1. Some individuals with MRKH syndrome also have abnormalities in other parts of the body; in these cases, the condition is classified as MRKH syndrome type 2. In this form of the condition, the kidneys may be abnormally formed or positioned, or one kidney may fail to develop (unilateral renal agenesis). Affected individuals commonly develop skeletal abnormalities, particularly of the spinal bones (vertebrae). People with MRKH syndrome type 2 may also have hearing loss or heart defects.

The cause of MRKH syndrome is unknown. Changes in several genes that are involved in development before birth have been identified in people with MRKH syndrome. However, each has been found in only a few affected individuals, and it is unclear whether these changes cause MRKH syndrome. Researchers are working to determine how genetic changes might lead to problems with development of the female reproductive system.

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 suspected that MRKH syndrome was caused by environmental factors during pregnancy, such as medication or maternal illness. However, subsequent studies have not identified an association with any specific maternal drug use, illness, or other factor. Researchers now suggest that in combination, genetic and environmental factors contribute to the development of MRKH syndrome, although the specific factors are often unknown.

It is also unclear why some affected individuals have abnormalities in parts of the body other than the reproductive system. Certain tissues and organs, such as the kidneys, develop from the same embryonic tissue as the Müllerian duct, and researchers suspect that problems during development could affect these organs as well.

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 the gene involved is usually unknown.

MRKH syndrome affects approximately 1 in 4,500 female newborns.