Vaginal bleeding in a misdiagnosed Mayer-Rokitansky-Küster-Hauser syndrome

The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, a spectrum of anomalies arising from incomplete development of the Müllerian ducts, is characterised by congenital aplasia of the uterus and upper part of the vagina, often in the absence of other phenotypical abnormalities. We report the case of a 13-year-old girl referred to our endocrinology unit after an incidental finding of uterine agenesis during laparoscopy to correct suspected ovarian torsion. Initial transabdominal ultrasonography found no uterus. Given her normal secondary sex characteristics, karyotype and hormone profile, MRKH syndrome was initially diagnosed. However, after vaginal bleeding compatible with menstruation, repeat transabdominal ultrasonography and MRI revealed a left-deviated unicornuate uterus.

urinary and genital tract disorders, reproductive medicine, congenital disorders

Disrupted Müllerian development can result in a wide range of congenital defects in the female genital tract1 2 that can occur in association with extragenital malformations involving mainly the urinary and skeletal systems.3 The most severe uterine malformation is agenesis, which forms part of the Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome.1 4 MRKH is characterised by agenesis or aplasia of the uterus and upper part of the vagina in phenotypically normal 46, XX females. The prevalence of MRKH syndrome remains controversial, but is generally estimated at 1 in 5000 live female births.5 6 We present the case of a 13-year-old girl with suspected MRKH syndrome. Case presentation A 13-year-old girl was referred to our endocrinology unit after an incidental finding of agenesis of the uterus during laparoscopic surgery to correct suspected ovarian torsion. Her personal history included prenatally diagnosed agenesis of the right kidney, and her family history included agenesis of the left kidney and left vas deferens in her father. She presented at the emergency department with abdominal pain and vomiting. Abdominal CT revealed an oval structure measuring about 50 mm×19 mm with small cystlike structures inside, which was thought to correspond to the right ovary. Laparoscopic surgery showed right fallopian tube torsion, but no uterus was seen (video 1). On physical examination, she had normal secondary sex characteristics, normal external genitalia and normal height. Abdominal ultrasonography could not find the uterus. Type II MRKH syndrome was diagnosed. A few months later, she presented vaginal bleeding compatible with menarche. Investigations Laboratory findings for follicle-stimulating hormone, luteinising hormone, oestradiol and androgens were within normal ranges. Her karyotype was 46, XX. On repeat transabdominal ultrasonography, a left-deviated unicornuate uterus without rudimentary uterine horns was observed, and both ovaries appeared normal. MRI confirmed the presence of a left unicornuate uterus and the absence of the right kidney (figure 1), thus ruling out MRKH syndrome. Differential diagnosis The features of MRKH syndrome overlap with those of various entities. The differential diagnosis should include 46, XY disorders of sexual development, such as complete androgen insensitivity syndrome and 17-hydroxylase/17-20-lyase deficiency due to biallelic CYP17A1 mutations.6 7 Other diagnoses that may be confused with Müllerian agenesis include other vaginal or uterine anomalies.7 The imaging appearance of the uterus and ovaries changes considerably with age. Before puberty, when hormone stimulation results in spectacular growth in the size of the uterus, increasing its length and its thickness, the uterus can be difficult or impossible to identify on ultrasonography.8 Treatment Effective management of MRKH syndrome starts with accurate diagnosis and screening for associated congenital anomalies. Attempts to improve dysfunction caused by genital anomalies should start with noninvasive vaginal dilation, which is effective in the vast majority of patients.7 In patients in whom dilation is unsuccessful, surgery is an option6 7; laparoscopic Vecchietti vaginoplasty yields the best outcomes with the lowest risk profile.4 Patients with a unicornate uterus are at a higher risk for endometriosis, preterm labour and breech presentation. Pregnancies in an obstructed or rudimentary uterine horn are also associated with placental attachment abnormalities and/or uterine rupture, with both spontaneous rupture and rupture during labour or induction being reported. Unicornuate uterus can also occur together with an ectopic ovary.9 Pregnancy outcomes in patients with unicornuate uterus are generally favourable, so reconstructive procedures to improve pregnancy outcomes are not usually recommended.2 9 However, a rudimentary horn with functioning endometrium can harbour an ectopic pregnancy, so noncommunicating rudimentary horns with endometrium are sometimes surgically removed.2 Outcome and follow-up A multidisciplinary approach is essential to ensure that gynaecological, sexual, fertility and psychological aspects of MRKH syndrome are adequately covered during follow-up.6 7 Although congenital uterine anomalies do not typically impair a woman’s ability to become pregnant, these anomalies are associated with abortion, preterm delivery and placental abnormalities.7 Until recently, women with MRKH syndrome could achieve biological motherhood only through gestational surrogates. However, uterus transplantation has provided new hope for these patients.6

The Müllerian ducts are essential in the development of the female reproductive system, differentiating into the fallopian tubes, uterus, cervix and upper two-thirds of the vagina. Any disruption in the process of development, fusion or resorption of the ducts will result in anomalies.6 Because the reproductive system develops in close parallel to the urinary tract, Müllerian defects are often associated with anomalies of the kidney and ureter.1 2 Müllerian duct abnormalities range from small anatomical variations to total aplasia.10 MRKH is the most common presentation of abnormal Müllerian development. The aetiology of MRKH syndrome is unclear. Most cases are sporadic; however, familial cases have also been described, where transmission apparently occurs in an autosomal dominant inheritance pattern with incomplete penetrance and variable expressivity.1 6 Familial clustering has been reported for MRKH as well as for other uterovaginal anomalies associated with renal anomalies, indicating that clinical presentations along the spectrum of renal and Müllerian anomalies might have a genetic component. Current knowledge of the genetic factors involved in MRKH syndrome and the wide range of uterovaginal malformations and associated malformations expressed phenotypically suggest a very heterogeneous aetiology. Most studies have used a candidate–gene approach, finding mutations in genes such as WNT4, HOXA genes, LHX1 and HNF1B. However, these findings apply only to a very small percentage of cases, and the role of genetics is still poorly understood.11 Various studies have reported muted GREB1L expression in patients with renal agenesis and Mullerian abnormalities with family histories of renal agenesis, underlining the importance of GREB1L in the development of both the female genital tract and the kidneys. Although our patient has yet to undergo genetic testing, this gene might be involved in our case.12 Pelvic ultrasonography is the imaging modality most often used for the initial assessment of gynaecological abnormalities, but MRI is the modality of choice for pelvic structures.13 MRI has clear advantages over ultrasonography, and MRI findings correlate closely with the findings at laparoscopy.6 10 A thorough knowledge of how hormonal changes affect the appearance of the uterus and ovaries at pelvic imaging is essential to differentiate between normal changes and pathological conditions. It is important to be careful when interpreting the morphology of the prepubertal uterus before the effects of hormone stimulation become evident. False-positive findings of uterine agenesis in prepubertal girls is a potential risk in imaging examinations.8 Patient’s perspective. First, I was afraid. My fear was related to the diagnosis, but especially to my parents’ reaction. They were very sad. Then I got my period, and I did not understand anything. My mother called the doctor immediately. Other imaging tests changed the diagnosis. I know that I may have problems with pregnancy in the future, but I am relieved. Learning points. Ultrasound imaging carries a risk of false-positive diagnosis of uterine agenesis/aplasia. Patients with suspected Müllerian anomalies should undergo MRI to ensure accurate diagnosis and to screen for associated malformations. A multidisciplinary patient-centred approach is essential to address gynaecological, sexual, psychological and infertility issues in patients with congenital uterine anomalies. Footnotes Contributors: MT, BN and RC participated equally in patient’s avaluation, MT and RC did the manuscript redaction and RC funding to publication. Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. Competing interests: None declared. Provenance and peer review: Not commissioned; externally peer reviewed.

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