A Rare Case of Herlyn-Werner-Wunderlich Syndrome in a Nulligravid

1
ABSTRACT

Herlyn-Werner-Wunderlich (HWW) syndrome is a very rare congenital anomaly

of the urogenital tract involving Mullerian ducts and Wolffian structures, and it is

characterized by the triad of didelphys uterus, obstructed hemivagina and ipsilateral renal

agenesis.1,2 Uterus didelphys is a type of lateral fusion disorder of mullerian ducts. Since

1922, mullerian duct anomalies have an incidence of 2–3%, while obstructing

hemivaginal septum and ipsilateral renal agenesis constitutes 0.16–10% of these

mullerian duct anomalies.3 It generally occurs at puberty and exhibits non-specific and

variable symptoms with acute or pelvic pain shortly following menarche, causing a delay

in the diagnosis. Clinically, these patients usually present after menarche with pelvic

pain, dysmenorrhea, and a palpable pelvic mass. 4 The pelvic mass is the collection of

blood products within the obstructed hemivagina. 5 Moreover, the diagnosis is

complicated by the infrequency of this syndrome, because Mullerian duct anomalies

(MDA) are infrequency encountered in a routine clinical setting. 1 Obstructed hemivagina

and ipsilateral renal anomaly (OHVIRA), also known as Herlyn-Werner-Wunderlich

syndrome, is a rare syndrome with only a few hundred reported cases described since

1922.5

This is a reported case of a 12-years-old, female, single, nulligravid, presented

with a history of increasing severity of cyclic pelvic pain, lasting for 2-6 days with every

menstrual cycle, hindering her daily activities. She was found to have a pelvo-abdominal

cystic mass. Transrectal and pelvic ultrasound was done with an initial diagnosis of

ovarian new growth and endometrial cyst. She was then eventually admitted for surgical

intervention.

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Keywords :Mullerian duct anomalies, Herlyn-Werner-Wunderlich syndrome, didelphys

uterus, obstructed hemivagina and ipsilateral renal agenesis.

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Introduction

Uterine malformations are heterogeneous group of congenital anomalies resulting

from abnormal development of Mullerian ducts. Herlyn-Werner-Wunderlich syndrome is

a rare condition that includes the triad of uterus didelfus, blind hemivagina and ipsilateral

renal agenesis.6 This triad was initially published in an English report in 2006. The

incidence of didelphys uterus, related to Herlyn Werner Wunderlich, is approximately

1/2000 to 1/28000, 43 % of the cases were unilateral renal agenesis. The exact etiology of

this syndrome is still unknown, but it may be caused by the abnormal development of

Müllerian and Wolffian ducts.7Its estimated occurrence is 0.1%–3.8%. The incidence of

unilateral renal agenesis in 1/1100 and 25-50% of affected women exhibits associated

genital abnormalities.1 The patient is usually young and presents with dysmenorrhea.

Early diagnosis and excision of the vaginal septum will relieve the patient of her

symptoms and prevents subsequent development of endometriosis and infertility but the

fact is, diagnosis is frequently delayed.8

Normally, development of Mullerian ducts depends on the completion of three

phases such as organogenesis, fusion, and septal resorption. Failure of organogenesis

results in uterine agenesis/hypoplasia or a unicornuate uterus. Fusion is characterised by

fusion of the ducts to form the uterus. Failure of this results in a bicornuate or didelphys

uterus. Septal resorption involves subsequent resorption of the central septum once the

ducts have fused. Defects in this stage result in a septate or arcuate uterus.9 Mullerian duct

anomalies consist of a set of structural malformations resulting from abnormal

development of the paramesonephric or Mullerian ducts. The embryological development

of the female reproductive system is closely related to the development of the urinary

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system, and anomalies in both systems may occur in up to 25% of these patients. Others

system that were affected by the malformations were gastrointestinal tract (12%) or

musculoskeletal system (10-12%).10 These anomalies have been associated with an

increased rate of miscarriage, preterm delivery and other adverse fetal outcomes.11,12

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Case Discussion

A12-years-old, female, single, nulligravid, presented with a history of severe

pelvic pain, lasting for 2-6 days with every menstrual cycle, hindering her daily activities.

Gynecologic history revealed menarche at 11 years of age, followed by 10 months of

severe dysmenorrhea since her first menstruation. The patient denied any recent

abdominal trauma, abnormal vaginal bleeding, nausea, vomiting or diarrhea. She always

take pain reliever for this complaint. Due to persistent increasing severity of

dysmenorrhea, she decided to consult a private gynecologist. Transrectal ultrasound was

requested and revealed a large anteverted uterus measuring about 8.6 x 4.7 cms, with a

markedly dilated endometrial cavity with fluid and low level echoes floating within,

thickness of which measures 3.1 cms, the cervix is also enlarged measuring 3.8 x 2.6 cms

with the endometrial cavity likewise filled with the same consistency of the endometrial

fluid. Then she was advised to follow up routinely.

Three months after, a transrectal ultrasound was repeated and revealed a 7.6 x

4.2 cm cystic mass at left adnexa to consider ovarian new growth, to consider

endometrial cyst. She was advised follow up scan after 3 months to monitor growth of

mass. 3 days prior to admission, on her second day of menstruation, she experienced

severe dysmenorrhea, prompting her to consult back to her private gynecologist. Rectal

examination showed a right-sided cystic, movable, non tender mass, measuring about

10x15 cm. The transrectal ultrasound was done and revealed 10.1 x 6.1 x 7.1cm

biloculated thick-walled cystic mass with homogenous medium level echoes in the right

adnexa, lateral to it was an elongated hypoechoic cystic mass with incomplete septation

measuring 7.4 x 3.6 x 6.4cm to consider ovarian new growth to consider endometrial

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cyst, hence the gynecologist recommended exploratory laparotomy. On laparotomy, there

was no ascitic fluid noted. Peritoneal washing was done and collected from 3 areas. There

is a left hemiuterus which is enlarged to 8x8cm with pinkish, smooth serosa. It was

adherent to the bowels and was in advertently ruptured revealing a chocolate like fluid.

The left fallopian tube was dilated to 15x5x4cm. On cut section, it extruded a chocolate-

like fluid. The left ovary is not grossly visible. The right horn of the uterus is small and

grossly normal together with the right fallopian tube and ovary.

On follow up, a KUB ultrasound was done and revealed:

the right kidney measures 10.7 x 3.9 x 5 cm with a cortical thickness of 1.4 cm, while the

left kidney is not visualized. No focal mass or free fluid noted in the left renal fossa.

The histopathology result was :

Gross / microscopic description:

The previously sectioned hemi-uterus of the uterus measures 6 x 6 x 3 cm. The serosa is

smooth. The endometrial lining is smooth. The wall is up to 1.3 cm thick. No mass is

noted. The previously sectioned dilated left fallopian tube measures 7 x 3 x 2 cm. The

lumen is smooth containing some blood clots. The left ovary is 3 x 2 x1 cm, showing 0.3

to 2 cm fluid containing cavities, the largest being hemorrhagic. Also submitted said to

contain “peritoneal fluid” consist of 8-9 milliliter of reddish, turbic fluid in 10ml

syringes. Smears and cell block done

Microsections : horn of corpus uteri show the endometrium lined by round to tubular

endometrial glands in cellular background. The myometrium shows interlaced smooth

muscle fibers. No mass is noted. The fallopian tube is dilated lined by flattened

epithelium and the wall shows mild diffuse mononuclear cell infiltrates containing blood

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clots. Negative for atypia and malignancy. The ovary shows hemorrhagic cyst layered by

hemosiderophages. Smaller cysts lined by granulosa cells are also noted. Negative for

atypia and malignancy. The peritoneal fluid smears and cell block show scattered

WBC’s, some fibrin and moderate number of erythrocytes. Negative for malignant cells.

Mullerian duct anomalies can happen to all women with percentage ranges

between 2-3%, the rate can increase to 10-15% in women with recurrent abortions. The

effect at the reproductive consequences to this group of women with this problem have a

very wide effect from the nearly normal reproductive life to sterility and sometimes even

the need for hysterectomy. Because of that, the gynecologist should have clear

knowledge about the types, diagnosis, surgical management if any, and the consequences

(reproductive and psychological) of the disease and its management.13

Embryologically, the female reproductive tract develops at the same time and

close to the urinary tract and kidneys from the development of two pairs of Wolffian

ducts (mesonephric duct) and Mullerian ducts (paramesonephric duct). Hence, female

reproductive tract anomalies may be associated with urinary tract anomalies such as renal

agenesis (commonest in Mullerian Duct Anomaly, with right sided prevalence), pelvic

kidney, duplication of the collecting system, or ectopic ureters or multicystic kidney. 14

The mullerian ducts differentiate to form the fallopian tubes, uterus, the uterine cervix,

and the upper 1/3 of the vagina. The two mullerian tubes come together in the midline,

the upper part of the two tubes spread apart to form each fallopian tube, the inner walls of

the mid-portion of the tubes disintegrate, forming a hollow cavity or uterus, and the inner

walls of the lower part of the mullerian ducts also disintegrate to form the cervix and

upper vagina. The lower 2/3 of the vagina develops from a completely different

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embryologic structure, known as the urogenital sinus. A wide variety of uterine

malformations can occur when this morphogenesis (development) is disrupted. They

range from uterine and vaginal agenesis (absence or failure to develop) to complete

duplication of the uterus and vagina, to malformations of only the uterus, to minor uterine

cavity abnormalities.14

Mesonephric duct anomalies cause lateral deviation of the ipsilateral

paramesonephric duct. These anomalies have been attributed to the failure of

paramesonephric ducts to fuse, which results in two separate hemiuteri, combined with

the failure of Mullerian tubercles to meet and perforate into the urogenital sinus, resulting

in an imperforate ipsilateralhemivagina. A didelphic uterus is due to developmental arrest

in the 8th week of gestation, which eventually affects the Mullerian and metanephric

ducts. Renal agenesis is hypothesized to be due to the developmental arrest in one of the

Wolffian ducts that ceases the genesis of the ipsilateral metanephric duct and disrupts the

fusion of the Mullerian ducts 14

There is a spectrum of uterine fusion anomalies that can occur during early

development. Lateral fusion defects are the most common type of Mullerian duct

abnormalities ranging from symmetric or asymmetric to obstructed or non-obstructed

fusion anomalies. This has ultimately lead to the classification scheme developed by the

American Fertility Society, which describes the appearance of the uterus given the

various fusion anomalies that can occur5

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 It is important to classify Mullerian Duct Anomaly properly because the

associated risks of poor pregnancy outcome and treatment can vary widely between

anomalies. The most common classification system is developed by the American

Society of Reproductive Medicine which have seven classes.9,15 Class I is called uterine

agenesis or hypoplasia of uterine. Class II results from complete or near-complete

arrested development of one of the Mullerian ducts, which can develop into four

subtypes: a).absent of rudimentary horn, b). non functional rudimentary horn, c). cavitary

communicating rudimentary horn and d). cavitary non communicating rudimentary horn.

Class III - uterine dydelphys; the failure of lateral fusion between vagina and two

Mullerian ducts. Class IV, bicornuate uterus, is divided into complete and incomplete

according to the division of the fundus. Class V- septate uterus. Class VI , arcuate uterus.

And Class VII is related with diethylstilbestrol. All of these classifications can be seen in

figure 1. In this report, the patient is classified as class III.

Herlyn-Werner-Wunderlich Syndrome

Obstructed hemivagina and ipsilateral renal anomaly (OHVIRA) which is also

also known as Herlyn-Werner-Wunderlich syndrome is a rare syndrome which has the

triad of renal agenesis, blind hemivagina and dydelphys uterus with only a few hundred

reported cases described since 1922.5 These triad are reported as Herlyn-Werner-

Wunderlich (HWW) syndrome which was initially published in an English report in

20061. The incidence of didelphys uterus, related to Herlyn-Werner-Wunderlich, is

approximately 1/2,000 to 1/28,000, and it is accompanied by unilateral renal agenesis in

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43% of cases. The incidence of unilateral renal agenesis is 1/1,100, and 25-50% of

affected women exhibits associated genital abnormalities.1

Herlyn-Werner-Wunderlich syndrome is a type of Müllerian duct anomalies

(MDA) associated with mesonephric duct anomalies resulting from non-development

(agenesia or hypoplasia), defective vertical or lateral fusion, or resorption failure of the

Müllerian (paramesonephric) ducts. Mullerian duct anomalies are estimated to have an

overall prevalence of 2% to 3% among all women, with an incidence of 1/200-600

among fertile women. Hypoplasia, as well as agenesis of the uterus and proximal vagina,

is at range of 5%-10% of Müllerian duct anomalies, didelphys uterus is approximately

11% of Müllerian duct anomalies. Renal tract anomalies which are associated with

Mullerian duct anomalies are 30% of cases. A complete or partial vaginal septum is

present in 75% of women with didelphys uterus.1

The exact cause, pathogenesis and embryologic origin of Herlyn Werner

Wunderlich syndrome are still unclear and remain a subject of discussion. Herlyn Werner

Wunderlich syndrome is usually discovered at puberty with non-specific symptoms, like

increasing pelvic pain, dysmenorrhea and palpable mass due to the associated

haematocolpos or hematometra, which result from retained, longstanding menstrual flow

in the obstruccted vagina..1

Diagnosing this syndrome is really difficult because of the regular menstruation

and the complains symptoms of cyclic dysmenorrhea was resolved by given anti-

inflammatory drugs, thus causing a delay in the diagnosis because they reduce or

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eliminate menses; ultimately, Herlyn-Werner-Wunderlich is an uncommon syndrome, not

often thought of as a diagnostic possibility1

. Usually, patients with Herlyn-Werner-Wunderlich have a normal onset of

menstrual cycles with bleeding from the unobstructed hemiuterus and most commonly

present at puberty, a few years after menarche, although it can present in adulthood as

primary infertility and has also been reported in a neonate, presenting as a mass

prolapsing per vaginum. The primary presenting symptom is cyclical lower abdominal

pain evolving into continuous severe pain with increasing distension of the obstructed

hemivagina which may be associated with a foul-smelling mucopurulent discharge. On

physical examination, a unilateral pelvic mass is usually felt twice as often on the right

side as on the left side.14

The potential complications of this syndrome are distinct in acute complications,

such as pyohematocolpos, pyosalpinx, or pelviperitonitis, and long-term complications,

such as endometriosis, pelvic adhesions and increased risk of abortion or infertility1

Herlyn-Werner-Wunderlich syndrome is a rare case of a mullerian anomaly. The

outcome of pregnancy in these patients reveals that 87% go on to have a successful

pregnancy, while abortions occur in 23% of the patients, 15% have preterm births, and

62% have full-term pregnancies and uncomplicated deliveries.1

Ultrasound and MRI are some modalities of choice for diagnosing, although the

gold standard is MRI5 In this patient we only do ultrasound because the first impression

was ovarian new growth to consider endometrioma. Currently, full resection of the

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vaginal septum is the main treatment for this syndrome. The use of laparoscopy to assess

exact uterine anatomy at the time of vaginal septectomy has been advocated previously;

however, the effect of the procedure on prognosis is not yet known. 7 In this patient, we

did a left hemihysterectomy with left salpingooophorectomy because on opening up, we

noted a grossly normal right uterus, fallopian tube and ovary, and an enlarged and

distended left uterus with a dilated tortous left fallopian tube

Since the patient still has a normal right hemi-uterus, fallopian tube, and ovary,

she is still capable having pregnancy. However, with only one kidney left, she is advised

to take good care of it.

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References:

1. Riccardo del Vescovo, Sofia Battiti, Valerio di Piola and et al.Herlyn

Werner wunderlich syndrome: MRI findings, radiological guide( 2

cases and literature review) and differtialdiagnosis.”BMC medical

imaging 2012.12:4 March 2012

2. KabiriDoron, YaaraArzy and Yael Hants. herlyn-werner-wuderlich

syndrome: uterus didelphys and Obstructed hemivagina with unilateral

renal agenesis. IMAJ • VOL 15 • JANUARY 2013

3. IOSR Journal of Dental and Medical Sciences (IOSR-JDMS) e-ISSN:

2279-0853, p-ISSN: 2279-0861.Volume 13, Issue 6 Ver. V (Jun.

2014), PP 01-03 www.iosrjournals.org

4. Moshiri Mariam, Adeel Rahim Seyal, and et al. Herlyn-Werner-

Wunderlich syndrome with a partially obstructed hemivagina.

Radiology Case Report. Volume 7 Issue 4. 2012

5. Cox D, Ching B. Herlyn –Werner-wunderlich syndrome; a rare case

presentation with pycolpos. Radiology Case 2012

6. Vilhena C, Jose L Metelloand et al. Helyn-Werner-

Wunderlichsyndrome : 3D ultrasonographic diagnosis in premenarche.

Middle East Fertility Society Journal. 2013

7. Zhu Lan, Na Chen, Jia-Li Tong, and et al. New Classification of

Herlyn-Werner-Wunderlich Syndrome. Chinese Medical Journal.

Volume 128 Issue 2. January 20, 2015

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8. S.A El agwany. Herlyn Werner Wunderlichsyndrome A case of

obstructed hemivagina with ipsilateral renal agenesis (OHVIRA

syndrome) and didelphic uterus. African Journal of urology. Desember

2013

9. M T Chandler, L S Machan et al. Mullerian duct anomalies : from

diagnosis to intervention. Br J Radiol. 2009 Dec; 82(984): 1034–1042.

10. Conti Sergio Ribeiro, RenataAssefTormena and et al. Mullerian duct

anomalies : review of current management. San Paulo Med J 2009

11. RamalingappaPadmasri, UrvashiBhatara and et al. Obstetric outcomes

in women with mullerian duct malformations. International journal of

reproduction, contraception, obstetrics and gynecology. March 2014

12. Kagan Elizabeth Arleo and Robert N Trolano. Complex Mullerian

Duct Anomalies Defying Traditional Classification : Lessons Learned.

Journal of fertilization. 2013

13. Elyan A and Saeed M. Mullerian duct anomalies:Clinical Concepts

ASJOG 20041:11

14. Karkera J Parag , PradnyaBendre and et al.HERLYN-WERNER-

WUNDERLICH SYNDROME: A CASE REPORT WITH REVIEW

OF LITERATURE.Vol 8 / No 3 / 2014

15. C Spenser Behr and Jesse L Courtier. Congenital Pelvic

Abnormalities. Radiographic. Volume 32. Issue 6. October 2012

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 TABLES

Hematology (01/23/2015)

Normal Values
Hemoglobin 122 120-160g/L
Hematocrit 0.37 0.37-0.43
RBC 4.56 4.2-5.4 x10/1
WBC 10.72 5-10x10/1
Differential Count
Segmenters 0.57 0.55-65
Lymphocytes 0.34 0.25-0.35
Platelet count 589,000 150,000-450,000
Blood type O positive

Urinalysis

Color Yellow
pH 6.0
Specific Gravity 1.010
Transparency Clear
Sugar Negative

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Protein Negative
RBC 0-1/hpf
WBC 0-1/hpf
Amorphous Urates Few
Epithelial Cells Many
Bacteria Moderate

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 ILLUSTRATIONS

Figure 1. Classification of Mullerian Duct Anomaly by American Society of Reproductive

Medicine

Figure 2. Illustration of a triad of uterine didelphys, obstructed hemivagina and

ipsilateral renal agenesis

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 PICTURES

CEPHALAD

Left hemi-uterus
8 x 8 cms

Right hemi-uterus

Left fallopian tube

18x5x4 cms

CAUDAD

Picture 1. Intraoperative Findings

8 x 8 cm 15x5x4cm

Left hemiuterus Left fallopian tube

Picture 2. Gross picture of the removed hemiuterus with dilated left fallopian tube

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Uterus Left fallopian tube

Picture 3. .Cut Section of the Hemiuterus

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Picture 4. .KUB ultrasound-Left kidney is not visualized

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