Male pseudohermaphrodite with persistent Mullerian duct: A radiologist's and patient's dilemma alike.

This case study highlights that how a disorder of sexual development when goes unnoticed at birth and unreported during childhood or adolescence can present with major problems and even complications in adulthood. Since our patient was young and in a childbearing age, he presented with bilateral undescended testes and orgasmic anejaculation when he first came to the hospital. Subsequently, having a normal 46XY karyotype but remnants of persistent Mullerian duct made him little confused about his identity. After giving him the confidence, that he was still a male and could lead the life he did previously, the explanation about future risk of malignancy in the intra-abdominal testes was another difficult task. Early detection and management of male pseudohermaphroditism with persistent Mullerian duct requires a co-ordinated approach of a team of endocrinologist, physician, surgeon and radiologist. Integrated imaging in the form of ultrasound, genitography and MRI is important in demonstrating the anatomy, classification, possible effects or congenital malformations in other organs, warning patients of any risk of neoplasia and guiding the clinician to plan other investigations, hormonal replacement or reconstruction surgery if required. Such a systemic approach that allays anxiety and gives psychological relief to the patient should be taken as it can deeply change the life of a person and their family.

Persistent Mullerian duct syndrome: rare presentation in an elderly man.

Persistent Mullerian duct syndrome has been described as a disease of internal male pseudohermaphroditism, a rare autosomal recessive disease, characterised by persistent Mullerian derivatives in patients with male pattern 46, XY karyotype and normal pattern virilisation. We present a case of an elderly man, who on evaluation for bilateral undescended testes was found to have a pelvic mass suggestive of malignant transformation of an undescended testis on imaging. On surgical exploration, uterus with multiple fibroids, bilateral fallopian tubes, cervix and bilateral atrophic testes were identified. Interestingly, in this case, imaging (contrastCT and MRI) had missed Mullerian structures due to varied presentation, but exploration and excision of the structures followed by their histopathology revealed uterine leiomyomas and confirmed other Mullerian structures (bilateral fallopian tubes, cervix) with bilateral testes.

Compound heterozygous mutations in the luteinizing hormone receptor signal peptide causing 46,XY disorder of sex development.

Testosterone production by the fetal testis depends on a functional relationship between hCG and the LH/chorionic gonadotropin receptor (LHCGR). Failure of the receptor to correctly respond to its ligand leads to impaired sexual differentiation in males. A phenotypically female patient with pubertal delay had a 46,XY karyotype and was diagnosed with 46,XY disorder of sex development (DSD). Novel compound heterozygous LHCGR mutations were found in the signal peptide: a duplication p.L10_Q17dup of maternal origin, and a deletion (p.K12_L15del) and a p.L16Q missense mutation of paternal origin. cAMP production was very low for both the deletion and duplication mutations and was halved for the missense mutant. The duplication and missense mutations were both expressed intracellularly, but at very low levels at the cell membrane; they were most likely retained in the endoplasmic reticulum. The deletion mutant had a very limited intracellular expression, indicating impaired biosynthesis. There was reduced expression of all three mutants, which was most marked for the deletion mutation. There was also decreased protein expression of all three mutant receptors. In the deletion mutation, the presence of a lower-molecular-weight band corresponding to LHCGR monomer, probably due to lack of glycosylation, and a lack of bands corresponding to dimers/oligomers suggests absent ER entry. This novel case of 46,XY DSD illustrates how different LHCGR signal peptide mutations led to complete receptor inactivation by separate mechanisms. The study underlines the importance of specific regions of signal peptides and expands the spectrum of LHCGR mutations.

A Novel Homozygous AMRH2 Gene Mutation in a Patient with Persistent Müllerian Duct Syndrome.

Persistent müllerian duct syndrome (PMDS) is characterized by the presence of müllerian duct derivatives in otherwise phenotypically normal males. Homozygous or compound heterozygous alterations in AMH or AMHR2 have been identified in approximately 88% of PMDS cases. We report on a male patient with bilateral undescended gonads, müllerian derivatives, and normal serum AMH levels. A novel homozygous missense mutation, c.119G>C;p.Gly40Ala, in exon 2 of AMHR2 was detected that supported the clinical diagnosis of PMDS.

Novel compound heterozygous variants in the LHCGR gene identified in a subject with Leydig cell hypoplasia type 1.

BACKGROUND: Leydig cell hypoplasia (LCH) is a rare disease and one of the causes of male disorder of sexual differentiation (DSD). Inactivating mutations in the luteinizing hormone/chorionic gonadotropin receptor (LHCGR) gene account for the underlying LCH pathogenicity. This study aimed to analyze the clinical presentation and diagnosis as well as highlight the molecular characteristics of a subject with LCH type 1. CASE PRESENTATION: Clinical data were collected from the subject and analyzed. Next generation sequencing of the immediate family pedigree using peripheral blood genomic DNA was performed, and the relevant mutations were verified with Sanger sequencing. We describe the case of a 5-year-old patient with DSD, presenting with a lateral inguinal hernia accompanied by abnormal hormone tests. The genetic analysis revealed novel compound heterozygous variants in the LHCGR gene, including a splice site mutation (c.681-1 G>A) and a frameshift variant (c.1582_1585del ATAT, p.Ile528*). CONCLUSIONS: We identified novel compound heterozygous variants in the LHCGR gene, and expanded the genotype-phenotype correlation spectrum of LHCGR variants.

Radiological Findings in Persistent Müllerian Duct Syndrome: Case Report and Review of Literature.

This case involved a 36-year-old adult male who presented with an unusual inguinal hernia in which the uterus and fallopian tubes were identified as contents of the inguinal hernia sac. These findings reflected a rare autosomal recessive developmental syndrome known as PMDS (persistent Müllerian duct syndrome). The diagnosis was established and confirmed via radiological-mainly MRI-investigation.

Coincidence of Persistent Müllerian duct syndrome and testicular tumors in dogs.

BACKGROUND: Persistent Müllerian duct syndrome (PMDS), a rare form of male pseudohermaphroditism in dogs, is an abnormal sexual phenotype in males that is characterized by the existence of a hypoplastic oviduct, uterus, and cranial part of the vagina. Dogs suffering from PMDS are often accompanied by cryptorchidism. To date, it has been mainly found in the Miniature Schnauzer breed. CASE PRESENTATION: In this report, two cases of PMDS with a malignant testicular tumor originating from cryptorchidism in breeds other than the Miniature Schnauzer breed are described. The patients were a seven-year-old male Maltese dog and a 17-year-old male mixed-breed dog weighing 3.8 kg. They also exhibited an enlarged prostate with or without abscess and an elevated serum estradiol level and were surgically treated to remove the testicular tumor and Müllerian duct derivatives. CONCLUSIONS: It is recommended that PMDS should be differentially diagnosed by ultrasonography and that orchiectomy be performed at an early age in patients suspected to have cryptorchidism to prevent the ectopic testes from becoming tumorous.

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

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 multidisciplinar 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.

Elevated testosterone levels in a racing horse due to an XY testicular disorder of sexual development.

A female thoroughbred successful in horse racing was positively tested for high testosterone values. This horse neither showed stallion-like-behaviour nor signs of ambiguous external genitalia. The karyotype of this horse was 2n = 64,XY and the sex-determining region of Y (SRY) PCR was positive. Hair samples tested for naturally testosterone revealed values normal for stallions, and tests for eight synthetic testosterone esters remained negative. The phenotype, ultrasonographic examination, hormone status, cytogenetic evaluation and molecular diagnostics lead to the diagnosis of an XY testicular disorder of sexual development (DSD) due to a complete androgen insensitivity syndrome. To our knowledge this is the first report about a thoroughbred in racing sports with an XY testicular disorder of sexual development. To date, intersex racing horses have never been described in thoroughbreds or a regulation for intersexes in regard to horse races has been issued.