Genetic Causes: Condition That Can Result In Absent Uterus and vagina


A percentage of females are born with a missing or underdeveloped vagina and uterus, and scientists are working to analyze the genes of hundreds of them to get a better idea about causes, improve genetic counseling and ideally treatment.

Abnormalities Of Vagina and Uterus

Developmental abnormalities of the vagina and uterus occur in about 7-10% of women, the most extreme is the absence of both in a condition known as Mayer-Rokitansky-Küster-Hauser, or MRKH, syndrome, says Dr. Lawrence C. Layman, chief of the Section of Reproductive Endocrinology, Infertility and Genetics at the Medical College of Georgia at Augusta University.

Individuals with MRKH can also have seemingly unrelated problems like only having one kidney as well as skeletal, heart valve and hearing problems. While MRKH is considered a genetic disorder, its genetics are poorly understood, Layman says. There's convincing evidence that variations in only two genes WNT4 and HNF1B are causative and those account for less than 1-2 % of cases and have only been studied in a handful of patients.

Layman is the principal investigator on a $2.6 million grant from the National Institute of Child Health and Human Development of the National Institutes of Health that will enable the use of high throughput sequencing and other techniques to look for more genetic causes of the condition that affects about 1 in 5,000 female babies. "We hope that we will find more causative genes. We think we will," Layman says.

It's also enabling the first comprehensive analysis of the frequency and spectrum of variants of the two known genes as well as four proposed genes, including ZNHIT3, discovered by Layman, in patients and their families. " The Researcher hopes we will get another 200 to 400 patients because sequencing a large number gives you a much higher chance of finding something," Layman says, noting the already great support of Beautiful You MRKH and its members.

Existing samples include blood from more than 40 patients with MRKH and three of their first-degree, unaffected relatives and another nearly 30 patients and two first-degree relatives. It's the family samples that will enable further exploration of how MRKH is inherited, since some families have more than one affected member but just how that occurs is unclear, Layman says.

The investigators suspect but want to confirm that it is an autosomal defect meaning not on a sex chromosome since it could be passed from males to females and females to males. "Every time there is a uterine abnormality you have to suspect a renal anomaly and every time there is a renal anomaly you have to suspect a uterine abnormality," Layman says.

Today's treatments include regular dilatations that will slowly enable an opening sufficient for intercourse. Openings also can be created surgically, but regular dilatation likely will still be necessary to maintain the opening. Uterine transplants also are done at a small number of centers to enable reproduction.