Herlyn-Werner-Wunderlich syndrome: clinical considerations and management

Herlyn-Werner-Wunderlich syndrome (HWWS), defined by the triad of uterus didelphys, obstructed hemivagina and ipsilateral renal agenesis, is a rare Mullerian duct malformation, usually diagnosed after menarche, when symptoms related to haematocolpos arise. We report a case of a 14-year-old patient who presented to the emergency department complaining of proctalgia and pelvic pain treated in our medical centre. Ultrasound and abdomino-pelvic MRI imaging studies confirmed the diagnosis. Treatment was surgical incision of the vaginal septum. At the follow-up visit, after the initial procedure, excess vaginal tissue was excised using a hysteroscopic approach during diagnostic vaginoscopy. Vaginoscopy-assisted treatment of the patient proved to be a safe and effective minimally invasive treatment modality that resulted in symptomatic relief and fertility preservation. In conclusion, although premenarche is asymptomatic in the vast majority of cases, HWWS would be optimally diagnosed in childhood to avoid acute late complications, although it is usually first diagnosed after menarche as a result of haematocolpos. Gynaecologists should consider the syndrome in the presence of pelvic mass, renal agenesis, menstrual changes and cyclic pelvic pain.

obstetrics and gynaecology, radiology, congenital disorders, surgery, ultrasonography

Herlyn-Werner-Wunderlich syndrome (HWWS) is a rare congenital disease consisting of anomalies of the female reproductive tract, which include uterus didelphys, unilateral blind hemivagina and ipsilateral renal agenesis. Its usual clinical presentation includes an ectopic ureter originated from a hypoplastic and minimally functional kidney in association with an ipsilaterally obstructed hemivagina.1–3 This is also known as obstructed hemivagina and ipsilateral renal anomaly.4 It occurs in 0.1% to 6% of women and is most commonly diagnosed at puberty due to pelvic and abdominal pain, and rarely presents in other age groups as primary infertility, pyometra, urinary obstruction or swelling in the ischiorectal region. Due to its rarity, there is often a delay in diagnosis by both primary and emergency care physicians, which increases the risk of complications such as endometriosis and infertility.4 5 It is important that physicians who treat patients for symptoms of urinary disease or endometriosis maintain a degree of suspicion for HWWS to ensure a timely diagnosis and avoidance of complications.6 We describe here the case of a 14-year-old girl who previously knew she had a single kidney, had recurrent painful abdominal symptoms during menstruation and who sought emergency treatment for acute abdominal pain at our clinic. Case presentation A 14-year-old girl was treated in the emergency department of the Jaraguá Maternity Hospital, Brazil, after having been referred from another service, complaining of pain on evacuation over the past 2 months. She also reported multiple visits to the emergency room in the previous month, almost always complaining of pain in the lower abdomen associated with dark-coloured urine. Menarche occurred at the age of 13 and her menstrual cycles were irregular with intense dysmenorrhoea. She had not yet been sexually active. Her medical history revealed a right renal agenesis and she had been recently treated for non-obstructive left nephrolithiasis with 5 mEq/day Litocit (potassium citrate monohydrate, Apsen, São Paulo, Brazil). Physical examination revealed tenderness and pain on palpation of the hypogastrium, apparently without pain on sudden decompression. The hymen appeared integrated on external inspection and during rectal examination it was possible to palpate a bulky mass at the bottom of the vaginal sac on the right side. Investigations Laboratory tests revealed a normal white blood cell count and coagulogram. An abdominal ultrasound (US) showed two individual endometrial cavities, apparently with two independent cervices, and was complemented by a pelvic CT scan on the day of admission. Imaging confirmed the absence of the right kidney and was suggestive of haematocolpos on the right side. In the vaginal canal there was intraluminal distension by hypoechoic and heterogeneous content with suspicion of uterus didelphys and haematocolpos. Differential diagnosis When uterovaginal obstruction results in significant distension, the imaging differential may include a large adnexal mass such as a cystadenoma or endometrioma.2 We informed the family and patient of these findings and the decision was made to perform a gynaecological examination under anaesthesia. The exam revealed an imperforate hymen and a very enlarged, bulging left uterine cervix. On speculum examination, the left hemivagina was patent, while the right side ended blindly. We performed a hymenectomy and a longitudinal vaginal septotomy and about 0.81 L of clotted blood was drained. The patient was then referred to the gynaecology outpatient clinic where she was medicated with medroxyprogesterone to suppress menstrual cycles until a pelvic MRI was obtained. Pelvic MRI revealed the following: a complex Mullerian anomaly with the absence of the right kidney and presence of a solitary left kidney (figure 1, arrows); two separate uteruses with two separate cervices, didelphys uterus; vaginal canal with alteration with partial septation (figure 2); the right uterine cervix demonstrated alterations in signal intensity with oedema related to recent surgical manipulation (figure 2); the left uterine cervix showed no alterations; both endometrial cavities demonstrated mild haemorrhagic content; the right fallopian tube was dilated with the presence of content compatible with recent haemorrhage (figure 3) and, associated, ascites were identified in the posterior and middle compartment of the pelvis compatible with recent haemorrhagic content (figure 4), suggesting the possibility of tubal reflux (figure 5). Treatment The patient underwent vaginoscopy prior to surgery to confirm the imaging findings and the planned procedure. Endoscopic examination through the septostomy orifice revealed a right-side patent hemiuterus with a single uterine cervix and a left-side cervix and hemiuterus. We were not able to evaluate the fallopian tubes and ostium by this method. A surgical resection of the septum using electrocautery was performed between the left and right hemivaginas and sutured with chromed catgut. A folley cathether was placed into each cervix to assure patency (video 1). Outcome and follow-up The procedure occurred without perioperative or postoperative complications. The patient was released from hospital 2 days after surgery after showing a satisfactory recovery and is being followed up in the outpatient clinic (infographic 1, figure 6).

Anomalies of the Mullerian duct (paramesonephric) are congenital anomalies of the female genital tract that result from the non-development or non-fusion of the Mullerian ducts or failure of the uterine septum to fuse during the sixth to ninth weeks of fetal life, and cause a wide range of malformations of the reproductive tract.7 HWWS is a combination of Mullerian duct anomaly and mesonephric duct malformation of the female urogenital tract.8 By the eighth week of gestation, the Mullerian ducts migrate to the midline and fuse to form the uterus, cervix and upper vagina. The intimate association between the mesonephric duct (Wolff duct) and the paramesonephric duct is extremely relevant from the clinical point of view because, in general, genetic-based malformations of these systems are associated with anomalies that also involve kidneys, ureters and the reproductive tract. It is estimated that up to 50% of women with uterine and vaginal anomalies also present with urinary tract anomalies. Renal agenesis occurs when one mesonephric duct fails to develop, which influences development of the ipsilateral Mullerian duct, implicating an aberration in mesonephric system differentiation in the aetiology of HWWS.4 6 7 Thus, abnormal differentiation of mesonephric and paramesonephric ducts may also be associated with kidney abnormalities. Renal agenesis is the most common anomaly, although there are descriptions in the literature of pelvic or horseshoe kidney, cystic renal dysplasia, duplication of the collecting system and ectopic ureters. Renal agenesis is predictive of an ipsilateral obstructive Mullerian anomaly in more than half of patients. These anomalies have a predominance for the right side, twice as frequently as anomalies on the left side. Such a relationship between female urogenital anomalies should prompt examination of the complete urogenital system when a genital anomaly is initially identified and vice versa.8 HWWS is classified according to the American Society for Reproductive Medicine as a class III uterine malformation and class IIa vaginal malformation.1 The first symptoms of the syndrome appear on average 6 to 9 months after menarche, since there is an externalised menstruation by one hemivagina, while the other, obstructed, hemivagina progressively forms a haematocolpos. The symptoms of dysmenorrhoea, cyclic abdominal pain and menstrual alteration are often reported by the patient. If the patient already had sexarche, there may be a complaint of dyspareunia. These symptoms, when not investigated, are commonly treated with Nonsteroidal Anti-inflammatory Drugs (NSAIDs) and combined oral contraceptives or isolated progestogens by professionals who are unaware of the underlying pathology. Thus, reducing the inflammatory process and inducing amenorrhoea lead to masking of the disease and delay the diagnosis.4 6 8 Delay in diagnosis may result in complications such as pyohaematocolpos, piosalpinge and peritonitis due to an ascending infection in the obstructed hemivagina from retained secretions or menstrual blood.5 6 8 9 Other complications include pelvic adhesions, endometriosis and infertility.2 Recurrent urinary tract infections may also occur due to compression of the bladder by haematocolpos. It should also be noted that patients are sometimes diagnosed with unilateral renal agenesis, even though in most cases the diagnosis is made together with the Mullerian anomaly. A palpable mass can be present in the lower abdomen and on pelvic examination there may be a perceive bulging on palpation of the septum. If the patient claims not to have had sex yet, perform only rectal examination, where paravaginal bulge can be detected.5 6 9 To investigate and diagnose suspected cases of HWWS, imaging exams should be requested including abdominal and pelvic US and CT, which are the most widely used tests. However, MRI is more sensitive for assessing soft tissue anatomy and for delineating subtle findings commonly found in congenital anomalies. Any surgical intervention should only be performed after these examinations. Laparoscopy is not mandatory, but may be useful to confirm the diagnosis when radiological findings are inconclusive, especially in cases of endometriomas with indication of resection.1 5 9 10 The treatment aims to relieve symptoms and re-establish anatomy to preserve sexual activity and fertility, which despite not being highly compromised, tends towards high rates of spontaneous abortion. In adolescents there is the option of postponing surgery and initially treating with gonadotropin-releasing hormone analogues or contraceptives that induce amenorrhoea, thus containing symptomatology, especially in cases of cervical atresia. Immediate treatment may include surgical incision and drainage of haematocolpos, if present in the diagnosis. For definitive surgical treatment, septotomy can be initially performed, followed by septoplasty, ensuring a complete vaginal septum resection.1 4 8 Obstetric outcomes for patients with HWWS include approximately 87% of patients who go on to have a successful pregnancy, although almost 27% of these patients are at risk for abortion or premature delivery, which is common. It is still necessary to evaluate and monitor planning of pregnancy in the case of HWWS, since there is a greater chance of the need for assisted reproduction techniques.1 6 8 11 Patient’s perspective. Since I was a child I knew I had a ‘different’ uterus and had only one kidney. My ‘kidney doctor’ told my parents I had a ‘bicornuate uterus’. This caused no symptoms until my first period. This changed after one year of my first menstruation, when I had menses I started feeling an annoying pain on my anus and lower part of abdomen. Sometimes I couldn't sit, lie down, or stand, I rolled on the floor in pain, it bothered me a lot, I wanted to go to school but I couldn't because it hurted a lot, and nobody found out what I had. My mother was told I needed an appointment with an ‘anus specialist doctor’ and he told us I had no problem on my anus. This doctor told me to do an abdominal ultrasound and then diagnosed what I had. I went to the hospital for more detailed examinations but it was still hurting a lot. They gave me injections for pain, but I had little relief of symptoms. After I had already received 5 or 6 pain medications, with no improvement of pain, I remember I fell on the floor such strong was the pain I had. At this time, they took me on a rush to the operating room. I did not even had time to be afraid of a surgery. I have stayed awake the whole surgery, I was surrounded by several professionals taking care of me. I thought the doctors would need to open my belly, I did not realized that they would do a surgery ‘down there’. When the surgery was over, I had to go to a room, where I waited for a while until I had a complete recovery. Today, after the two surgeries I was submitted, I am feeling very happy, because the pain has gone. When I was recovering from the operation at home I had some discomfort. I couldn't do anything outside, I could not go to school for a while but now everything is back to normal and the surgery results were great. I think it’s not that bad having a uterus like this, because it only disturbed me once, and I think I had a privilege for being one of few cases in the world and you (the doctors) are privileged ones for being able to take care of such a rare case. When I grow up, I want to be a surgeon to help girls with the same problem I have. I really liked how the procedure and the process was managed and how good I feel today went. I was taken care of by good doctors, and I was in good hands. The experience was very good for me, and today I can go back to doing what I couldn't do before, as if that had never happened. Learning points. Herlyn-Werner-Wunderlich syndrome is a rare congenital anomaly characterised by uterus didelphys, blind-ended vagina and ipsilateral renal agenesis. It is usually asymptomatic until menarche, and is often diagnosed late when haematocolpos and acute symptoms are present. It is essential that gynaecologists be aware of this syndrome whenever cases of pelvic masses, renal agenesis, menstrual changes and cyclic pelvic pain are encountered. Imaging tests such as ultrasound and especially MRI are fundamental for characterisation of abnormalities and better surgical planning. Acknowledgments We would like to thank Doctors Mariana Godói, Guilherme Sapia and Camila Schipanski for their valuable support for the patient’s treatment and gratefully acknowledge the exceptional support by the residents and nursing staff of the Gynecology and Obstetrics Department, Hospital e Maternidade Jaraguá. We also thank Maria Júlia Vianna Marçal and Yohanna Machado for producing the video that accompanies this work, the Estácio School of Medicine Clinical research group, Daniela Badia de Souza and Carville G Bevans, PhD for assistance in preparing the manuscript and English language polishing. Footnotes Twitter: @waghorst Contributors: WH and BS conceived of the study. BS and GT wrote the manuscript with support from WH and RCdM analysed imaging findings. WH helped supervise the project. All authors contributed to refinement of the case report and approved the final manuscript. All authors agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. 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. Patient consent for publication: Parental/guardian consent obtained. Provenance and peer review: Not commissioned; externally peer reviewed.

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