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.

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.

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.

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.

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.

Analysis of anti-Müllerian hormone (AMH) and its receptor (AMHR2) genes in patients with persistent Müllerian duct syndrome / Pesquisa de mutações nos genes do hormônio antiMülleriano (AMH) e do seu receptor (AMHR2) em pacientes com síndrome de persistência dos ductos Müllerianos

OBJECTIVE: To screen for mutations in AMH and AMHR2 genes in patients with persistent Müllerian duct syndrome (PMDS). PATIENTS AND METHOD: Genomic DNA of eight patients with PMDS was obtained from peripheral blood leukocytes. Directed sequencing of the coding regions and the exon-intron boundaries of AMH and AMHR2 were performed. RESULTS: The AMH mutations p.Arg95*, p.Arg123Trp, c.556-2A>G, and p.Arg502Leu were identified in five patients; and p.Gly323Ser and p.Arg407* in AMHR2 of two individuals. In silico analyses of the novel c.556-2A>G, p.Arg502Leu and p.Arg407* mutations predicted that they were harmful and were possible causes of the disease. CONCLUSION: A likely molecular etiology was found in the eight evaluated patients with PMDS. Four mutations in AMH and two in AMHR2 were identified. Three of them are novel mutations, c.556-2A>G, and p.Arg502Leu in AMH; and p.Gly323Ser in AMHR2. Arq Bras Endocrinol Metab. 2012;56(8):473-8.

OBJETIVO: Analisar os genes AMH e AMHR2 em indivíduos com síndrome de persistência dos ductos de Müller (SPDM). PACIENTES E MÉTODO: Amostras de DNA genômico de oito pacientes com SPDM foram obtidas de leucócitos de sangue periférico. Sequenciamento direto da região codificadora e das áreas intrônicas próximas aos éxons dos genes AMH e AMHR foi realizado. RESULTADOS: As mutações p.Arg95*, p.Arg123Trp, c.556-2A>G e p.Arg502Leu no gene AMH foram identificadas em cinco pacientes e as mutações p.Gly323Ser e p.Arg407* no gene AMHR2, em dois indivíduos. As análises in silico das mutações c.556-2A>G, p.Arg502Leu e p.Arg407*, não descritas anteriormente na literatura, previram que elas são deletérias e possivelmente a causa da doença. CONCLUSÃO: Uma provável etiologia molecular foi encontrada nos oito pacientes portadores de SPDM avaliados. No gene do AMH foram identificadas quatro mutações e no AMHR2, duas mutações. Três das seis mutações encontradas são mutações novas, c.556-2A>G e p.Arg502Leu no gene AMH; e p.Gly323Ser no AMHR2. Arq Bras Endocrinol Metab. 2012;56(8):473-8.

Persistent mullerian duct syndrome.

Persistent mullerian duct syndrome is a rare form of internal male pseudohermaphroditism in which mullerian duct derivatives are present in a genotypic (46XY) and phenotypic male. We report a rare case of persistent mullerian duct syndrome in an adult fertile male in whom mullerian duct derivatives (uterus and fallopian tubes) were found in the right hernia sac at herniotomy.

Persistent Mullerian Duct Syndrome in a Boy with Transverse Testicular Ectopia: a Case Report / 대한비뇨기과학회지

Persistent mullerian duct syndrome is characterized by the presence of mullerian structures in male subiects with normal penile and scrotal development. A deficiency of activity of a mullerian inhibiting substance during gestation is believed to be responsible for this syndrome. To date approximately 150 cases of persistent mullerian duct syndrome have been reported and the syndrome of transverse testicular ectopia with persistent mullerian duct structures is much rarer. In Korea, this is the fourth case to be reported. We report a case of persistent mullerian duct syndrome with transverse testicular ectopia in a 7 month-old-boy. Both testes were in the right side of scrotum but no epididymises were found there, which resulted in the disruption of normal relationship between the was and testis. Regarding there was no fertility, mullerian duct structures were removed.

A Case of Persistent Mullerian Duct Syndrome / 대한비뇨기과학회지

Persistent mullerian duct syndrome is an uncommon condition which is a consequence of a defect in either the production or the peripheral action of mullerian inhibiting substance(MIS). We experienced a case of persistent mullerian duct syndrome of a 28 year-old patient who had a testis and female internal genital organs such as mullerian duct remnant in right scrotum with inguinal hernia and an undescended testis in left side. The patient was managed by resection of the left testis and the female internal genital organs such as mullerian duct remnant, and orchiopexy for right undescended testis.

A Case of Persistent Mullerian Duct Syndrome / 대한비뇨기과학회지

Male pseudohermaphroditism can result from defects in androgen synthesis, androgen action, and mullerian duct regression, and from other uncertain causes. A rare form of male pseudo- hermaphroditism is characterized by the persistence of mullerian derivative in phenotypic male. The retention of mullerian structures can be ascribed to failure of the Sertoli cells to synthesize mullerian duct inhibitory factor, a defect in the response of the duct to that factor, or possibly discordant timing of the release of that factor. We experienced a case of persistent mullerian duct syndrome, which is phenotypically normal male with a right inguinal hernia and a left undescended testis, bilateral fallopian tubes and a uterus. Herein we report a case of early orchiopexy with this syndrome and brief review of the literatures.

A case of persistent Mullerian duct syndrome / 대한비뇨기과학회지

A small number of patients have been described in whom normal male development of the external genitalia has occurred but whom the Mullerian ducts persist. The retention of Mullerian structures can be ascribed to the failure of the Sertoli cells to synthesize Mullerian duct inhibitory factor or to a defect in the response of the duct to that factor. We experienced a case of persistent Mullerian duct syndrome. which is phenotypically normal male with bilateral undescended testes, bilateral fallopian tubes and a uterus. Herein we report a case with brief review of the literatures.

A case of persistent Mullerian duct syndrome / 대한비뇨기과학회지

A small number of patients have been described in whom normal male development of the external genitalia has occurred but whom the Mullerian ducts persist. The retention of Mullerian structures can be ascribed to the failure of the Sertoli cells to synthesize Mullerian duct inhibitory factor or to a defect in the response of the duct to that factor. We experienced a case of persistent Mullerian duct syndrome. which is phenotypically normal male with bilateral undescended testes, bilateral fallopian tubes and a uterus. Herein we report a case with brief review of the literatures.