Recent advances in the treatment of persistent Müllerian duct syndrome / 中华泌尿外科杂志

Male sex differentiation is driven by 2 hormones produced by the fetal testis, testosterone and anti-Müllerian hormone(AMH), responsible for the regression of müllerian ducts in male fetuses. Mutations inactivating AMH or its receptor AMHR2 lead to the persistent müllerian duct syndrome(PMDS) in otherwise normally virilized 46, XY males. Further assessment was carried out when suspicion of PMDS arose from physical examination which revealed that the testis crossed to the contralateral side of the body. Further examination include ultrasound, AMH concentration, karyotype, and gene sequencing. Once PMDS is considered, there is no need to perform the gonads biopsy. The optical surgery methods include one-stage cryptorchidism and hernia curation, and at the same time.Stripping/destroying the mucosa of the retained müllerian remnants to reduce the risk of malignancy and, simultaneously, to prevent the damage to vas deference.

Surgical management and molecular diagnosis of persistent Müllerian duct syndrome in Chinese patients / 亚洲男科学杂志(英文版)

Persistent Müllerian duct syndrome (PMDS) is a rare clinically and genetically overlapping disorder caused by mutations in the anti-Müllerian hormone (AMH) gene or the anti-Müllerian hormone receptor type 2 (AMHR2) gene. Affected individuals present uterus and tubes in normally virilized males and are discovered unexpectedly during other surgeries. Since it is rare and complex, a definitive clinical diagnosis can be missed, and there are no guidelines regarding how to deal with the uterus. In the present study, exome sequencing and Sanger verification were performed for causal variants in 12 PMDS patients. Preoperative diagnoses were made by positive exome sequencing in 8 patients. Of them, 7 patients evoked on the basis of ultrasound indicating bilateral testes on the same side of the body. Twelve different AMH variants (2 frameshift/nonsense, 1 deletion, 8 missense, and 1 in-frame) in 9 patients and 6 different AMHR2 variants (5 missense and 1 splicing) in 3 patients were identified. Seven variants were classified as "pathogenic" or "likely pathogenic", and 4 of them were novel. All but two patients with AMH defects showed low serum AMH concentrations, but all patients with AMHR2 defects showed elevated AMH levels. During surgery, an abnormal vas deferens was observed in half of the patients. Eight patients underwent orchidopexy with uterine preservation. Of them, 2 patients presented complications including irreducible cryptorchidism, and 3 patients developed Müllerian remnant cysts. Three patients underwent subtotal hysterectomy. Of them, one patient had complication of injury to the vas deferens, and one had hemorrhage after operation. This is the first report of PMDS involving a large Chinese population. The present study not only expands the variation spectrum but also provides clinical experience about the management of the uterus.

Neovagina creation using sigmoid colon in vaginal agenesis: a case report and review of literature

Mullerian duct anomalies are rare and can present with abnormalities in upper vagina, cervix, uterus, and fallopian tubes. The exact incidence of cervicovaginal agenesis is unknown and there are very few cases recorded in the literature. Authors report a 12-year-old girl referred from gynaecologist with chronic cyclical abdominal pain with underdeveloped, geniatilia and developed secondary sexual characters. Radiological investigations showed hypoplastic cervix with hematometra and left hemato salpinx. A definitive repair with creation of a neovagina using a sigmoid colon segment was performed in a single stage. Many techniques are described for reconstruction of cervicovaginal canal. Use of colon in creation of a neovagina is described by authors. Here we report a case of complete vaginal agenesis presenting with Hematometra-Hematosalpinx where a neovagina was created using a segment of sigmoid colon. Single staged surgery for neovagina creation using segment of sigmoid colon offers a promising and safe alternative for cervicovaginal agenesis.

Unicornuate uterus with functional non communicating rudimentary horn: a refractory cause of dysmenorrhea

Mullerian duct anomalies are rare. Unicornuate uterus with a non-communicating rudimentary horn is a rare type of mullerian duct anomaly which occurs due to defective fusion of malformed duct with contralateral duct. The incidence is approximately 1:100000. Patient usually remain asymptomatic due to the absence of functional endometrium in most of the cases. If the rudimentary uterine horn has an endometrium lined uterine cavity and doesn’t communicate externally then the signs and symptoms of obstructed menstruation appears, as soon as menarche begins. It will be associated with severe dysmennorhoea and hematometra. Other complications may be abdominal lump, chronic pelvic pain, infertility, endometriosis, adenomyosis and ectopic pregnancy in rudimentary horn. Authors are presenting a case of refractory dysmenorrhea with lump abdomen in a patient with unicornuate uterus with functional non communicating horn. In a patient with refractory dysmenorrhea mullerian duct anomaly should be kept as differential diagnosis.

Study and clinical evaluation of 25 cases of primary amenorrhea

Background: Primary amenorrhea is absence of menstruation and secondary sexual characters by age of 14 years primary amenorrhea is < 1%. Development of female genital organs takes place from mullerian DUCT (paramesonephric duct). The objective of this study was to note the various causes, complete clinical picture and the management in 25 such cases of primary amenorrhea.Methods: This is a prospective study done in 25 cases. They were investigated, managed and patients were called up for follow up for their response to treatment.Results: Out of 25 cases studied, maximum cases presented at 14-16 years of age, with chief complaint of primary amenorrhea, out of which 8% were married, 44% cases were of MRKH syndrome which was the most common cause of primary amenorrhea.Conclusions: Amenorrhea has got multi factorial etiology. For patients with amenorrhea physical examination should focus on pubertal development and possible genital out flow obstruction.

Recurrent hematometra with endometriosis in an adolescent girl: a case report

Hematometra is a collection or retention of blood in the uterine cavity. This condition is most commonly associated with congenital uterine anomalies that result from abnormal formation, fusion or resorption of Mullerian ducts during fetal life or may be due to prior surgical procedures, causing an obstruction of the genitourinary outflow tract. We report an unusual case of hematometra with endometriosis secondary to cervical stenosis. This is a rare and important case report due to the complexity of diagnosis as cervical stenosis was not presented as primary amenorrhoea as its usual presentation. This case was successfully managed by Hysteroscopic cervical dilatation under USG guidance followed by transcervical insertion of a catheter to prevent recurrent stenosis.

Novel homozygous mutation in a colombian patient with persistent müllerian duct syndrome: expanded phenotype

ABSTRACT The anti-Müllerian hormone triggers the regression of uterus and fallopian tubes in male embryos; if there are problems in the synthesis or action of this protein, Müllerian structures persist in an otherwise phenotypic male. The most frequent clinical presentation of Persistent Mullerian Duct syndrome is cryptorchidism and inguinal hernia. The few cases reported in adults are incidental findings or inguinal hernias. However, we present an adult male with history of bilateral cryptorchidism with unsuccessful orchidopexy, who presents with a large abdominal mass with the finding of a seminomatous tumor and persistence of Müllerian structures, in whom the variant c.916delC (p.Leu306Cysfs*29) in the AMHR2 gene not previously reported was documented.

Case report of a posterior vaginal wall Mullerian cyst

Mullerian cysts are common types of vaginal cysts, which are small and mainly asymptomatic. Sometimes they present as large symptomatic cystic lesions arising issues of differential diagnosis. They are congenital cysts found anywhere along the length of development of Mullerian duct, occurring typically during the conventional gynaecological examination. Authors report of a premenopausal woman presenting with a small asymptomatic, palpable cystic lesion in the posterior vaginal wall, found during the gynaecological re-examination one month after an open surgery for an ovarian endometrioma excision. The whole lesion was 0.4cm and surgically excised under general anesthesia. Postoperative period was completely uncomplicated. Pathology affirmed a benign Mullerian cyst. Although the majority of vaginal cysts may be asymptomatic, a complete excision is required especially in cases of suspected malignancy or other pathology. Clinical examination and imaging are not enough for determining the pathology and a histopathology confirmation is always necessary.

Long-term follow-up on MURCS (Müllerian duct, renal, cervical somite dysplasia) association and a review of the literature

Müllerian duct aplasia-renal aplasia-cervicothoracic somite dysplasia (MURCS) association is a unique development disorder with four common types of malformations that include uterine aplasia or hypoplasia, renal ectopy or agenesis, vertebral anomalies, and short stature. The majority of MURCS patients are diagnosed with primary amenorrhea from late-adolescence. However, a few cases with MURCS association are not well diagnosed during childhood and long-term outcomes are not well reported. We report a case of an 8-year-old girl with MURCS association who presented with recurrent urinary tract infections and multiple congenital malformations, and who was followed for 10 years until adulthood. MURCS association should be considered as one of the differential diagnoses when evaluating prepubertal females with vertebral and renal malformations.

Leiomyoma development in Mayer-Rokitansky-Küster-Hauser syndrome: a case report and a narrative review of the literature

The development of leiomyomas on the grounds of an aplastic/hypoplastic uterus in patients with Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) has been rarely described. We report the first case of development of multiple leiomyomas in a patient with MRKHS complicated with pulmonary valve stenosis, and we present a narrative review of the existing literature. A 44-year-old patient with MRKHS attended our clinic because of pelvic pain, which was attributed to a pelvic mass found on ultrasound. Magnetic resonance imaging revealed a multinodular mass, indicating either ovarian pathology or the presence of leiomyomas. Exploratory laparotomy was performed, and multiple solid masses on the grounds of two rudimentary uterine buds were observed. Histological analysis revealed multiple leiomyomas arising from parametrial or paratubal tissue. We searched medical databases for articles relevant to leiomyomas and MRKHS. We present a review of the current literature and summarize the clinical manifestation, diagnosis, management, and histopathological findings of all the cases described. We underline that it is important for gynecologists to be aware of this rare clinical entity, and symptomatic leiomyomas cannot be excluded in patients with MRKHS.

Young or old, this condition may unfold: The use of ultrasound in the diagnosis of a wide spectrum of Herlyn Werner Wunderlich Syndrome, a case series / Philippine Journal of Obstetrics and Gynecology

@#Herlyn-Werner-Wunderlich syndrome, characterized by uterus didelphys with blind hemivagina and ipsilateral renal agenesis, is a rare Mullerian duct anomaly. This case series shows a wide spectrum of the condition, one presenting in an adolescent, managed conservatively and the other in the perimenopausal age group given a more definitive management. The first case is an 18-year- old nulligravid who manifested with progressive dysmenorrhea and foul smelling vaginal discharge a few years after menarche. She subsequently underwent vaginal septotomy followed by diagnostic hysteroscopy. On the other hand, the second case is a 46- year-old nulligravid whose chief complaint is a foul smelling vaginal discharge and consequently went through a total abdominal hysterectomy with salpingo-oophorectomy. To our knowledge, the second case is the only patient diagnosed in the perimenopausal stage and underwent a total hysterectomy. Ultrasound is the first-line imaging modality used in both cases and its merits are highlighted to prove its importance and diagnostic value in the workup of this condition.

Male pseudohermaphroditism with os clitoris in three dogs

Two American Cocker Spaniels and one Bichon Frise were presented to our veterinary teaching hospital with an enlarged clitoris. Diagnostic imaging showed that the structure was composed of bony material. Exploratory laparotomy revealed uterine-like structures and testes which had an epididymis unilaterally. Surgical removal of internal genitalia, gonads and protruded clitoris were performed well. Histological evaluation revealed; inactive testes, female internal genital tracts with ambisexual ductal remnants, and prominent ossification in the clitoris. All 3 cases were diagnosed with male pseudohermaphroditism. In author's knowledge, this is the first report in Bichon Frise dog with os clitoris and also, it describes not common cases in small dog breeds with os clitoris.

Herlyn-Werner-Wunderlich Syndrome: A Mini-review

Herlyn-Werner-Wunderlich (HWW) syndrome is a rare congenital malformation syndrome that is characterized by a triad of uterine didelphys, blind hemivagina, and ipsilateral renal agenesis. There is a wide variety of phenotypic presentation which is recognized as a spectrum of disease rather than a separate entity. The exact incidence and pathogenesis of HWW syndrome are yet to be investigated. While this disease typically involves adolescent girls who present with abdominal pain or a pelvic mass that is secondary to hematocolpos, nowadays, a majority of potential patients with HWW are being prenatally screened for renal anomalies. Therefore, it is recommended to search for uterovaginal anomalies whenever a multicystic dysplastic kidney or the absence of a kidney is noted in a newborn female, and the role of pediatric nephrologists has become ever more important for early recognition of the disease.

The wandering twin: A case of a uterine didelphys with the obstructed hemiuteri in the anterior abdominal wall

@#Mullerian duct anomalies (MDAs) are congenital defects of the female genital system that arise from abnormal embryological development of the Mullerian ducts. A didelphys uterus, also known as a "double uterus," is one of the least common amongst the MDAs. Reported here is a case of a 16 year old female with a uterus didelphys with the obstructed left hemiuteri adherent in the anterior abdominal wall, and an endometriotic cyst on the same side. She underwent hysteroscopy-guided vaginoscopy, laparoscopic left hemihysterectomy, left oophorocystectomy. Cases such as these require careful preoperative planning and diagnostic imaging for more accurate diagnosis and, hence, for the most appropriate surgical procedure to be carried out. 3D ultrasonography and Magnetic Resonance Imaging have been the most widely used imaging techniques. The goals of management are to relieve the symptoms of obstruction and to restore the normal anatomy as much as possible in order to provide the best chance for future fertility.

Surveyor assay to diagnose persistent Müllerian duct syndrome in Miniature Schnauzers

Persistent Müllerian duct syndrome (PMDS) is a pseudohermaphroditism in males characterized by the presence of Müllerian duct derivatives. As PMDS dogs often lack clinical symptoms, a molecular diagnosis is essential to identify the syndrome in these animals. In this study, a new molecular method using DNA mismatch-specific Surveyor nuclease was developed. The Surveyor nuclease assay identified the AMHR2 mutation that produced PMDS in a Miniature Schnauzer as accurately as that obtained by using the conventional method based on restriction digestion. As an alternative to the current molecular diagnostic method, the new method may result in increased accuracy when detecting PMDS.

Persistent Mullerian Duct Syndrome: a rare entity with a rare presentation in need of multidisciplinary management

ABSTRACT Main findings: A typical male looking adolescent with a legal female gender assignment presented with haematuria. Investigations led to the diagnosis of Persistent Mullerian Duct Syndrome. The condition is indeed a rare entity that needs a multidisciplinary team management. Case hypothesis: A case of Persistent Mullerian Duct Syndrome undiagnosed at birth because karyotyping was defaulted, thus resulting in a significant impact on the legal gender assignment and psychosocial aspects. Promising future implications: The reporting of this case is important to create awareness due to its rarity coupled with the rare presentation with hematuria as a possible masquerade to menstruation. There were not only medical implications, but also psychosocial and legal connotations requiring a holistic multidisciplinary management.

Persistent Müllerian duct syndrome of mixed anatomical variant (combined male and female type) with mixed germ cell tumor of left intra‑abdominal testis.

Persistent Müllerian duct syndrome (PMDS) is a rare form of internal male pseudohermaphroditism characterized by retention of Müllerian duct derivatives in a phenotypically and karyotypically male patient. Deficiency of anti‑Müllerian hormone (AMH) secretion or resistance to AMH action due to defective AMH‑II receptor is presumed to cause such syndrome in the majority of cases. About 158 PMDS cases have been reported so far, out of which 31 cases are associated with testicular neoplasms. Herein, we describe an interesting case of young male initially diagnosed and treated for inguinal hernia, but finally diagnosed as “PMDS of mixed anatomical variant (combined male and female type) with mixed germ cell tumor of left intra‑abdominal testis” comprising components of seminoma and yolk sac tumor and treated successfully.

Scar endometriosis – A clinical rarity.

Scar endometriosis is a rare occurrence. Endometriosis is presence of endometrium at ectopic sites, other than the uterine cavity. Though the common sites of endometriosis are pelvic structures, extra pelvic endometriosis is occasionally seen. But presence of endometriosis in previous incision scars is extremely rare. Endometriosis in abdominal incision sites following Cesarean scions, hysterectomy, ovarian endometrioma removal are described. Very few cases of endometriosis at episiotomy site are also described in literature. This case report describes two such cases of scar endometriosis. The first case had scar endometriosis following a laparotomy done for rudimentary horn pregnancy. The second case had endometriosis in the scar of previous laparscopic surgeries, performed for ovarian endometrioma.

Revisión pictográfica de las anomalías de los conductos de Müller por resonancia magnética / Pictographic review of Müllerian duct anomalies by magnetic resonance imaging

Las anomalías útero-vaginales o müllerianas son un grupo de patologías congénitas que se originan por un defecto del desarrollo, fusión o canalización de los conductos de Müller en la etapa embrionaria, excepcionalmente pueden deberse a una alteración adquirida. La mayoría se diagnostica en forma tardía, como resultado de estudios de infertilidad o complicaciones obstétricas tempranas o tardías. La resonancia magnética (RM) es un examen no invasivo, que no utiliza radiación ionizante, con una alta resolución de contraste, que permite la evaluación multiplanar de las malformaciones müllerianas, permitiendo su aproximación diagnóstica y caracterización, complementando otras técnicas de imágenes como la histerosalpingografía y la ecografía ginecológica. El radiólogo debe estar familiarizado con las alteraciones anatómicas de los genitales femeninos y su representación en RM permitiendo un diagnóstico diferencial apropiado, oportuno y en consecuencia, un tratamiento adecuado. Este artículo describe los hallazgos en este grupo de malformaciones según la clasificación de la American Fertility Society, la más utilizada en la literatura actual.

The uterus-vaginal or Müllerian anomalies are a group of congenital diseases that are caused by a developmental defect, merger or channeling of Müllerian ducts in the embryonic stage, exceptionally may be due to an acquired disorder. Most belatedly diagnosed as a result of studies of infertility or early or late obstetric complications. Magnetic resonance imaging (MRI) is a noninvasive test that does not use ionizing radiation, with high contrast resolution, which allows multiplanar evaluation of Müllerian malformations, allowing its diagnostic approach and characterization, complementing other imaging techniques such as hysterosalpingography and gynecological ultrasound. The radiologist should be familiar with the anatomical abnormalities of the female genitalia and its representation in MRI, allowing an appropriate and timely differential diagnosis, and consequently, an appropriate treatment.

Acute urinary retention caused by seminoma in a case of persistent Mullerian duct syndrome.

Urinary symptoms have been described secondary to a pelvic mass originating from the ovary, uterus, cervix, prostate, or rectum. Persistent Mullerian duct syndrome is a rare form of intersex disorder, characterized by the presence of uterus and fallopian tubes in an otherwise 46 XY male. We report an adult male with bilateral cryptorchidism and a pelvic mass, who presented with acute urinary retention, and was diagnosed with a seminoma of the right testis, intratubular germ cell neoplasia of the left testis with the presence of Mullerian remnants. Pelvic mass was caused due to seminoma is a rare cause of urinary retention.