A Rare Case of 46, XX (SRY+) With Normal Male Stature and Unilateral Absence of the Vas Deferens

Objective: This study aimed to investigate the cause of primary infertility in a rare case with unilateral absence of vas deferens. Case report: A 35-year-old man was presented to the Infertility Clinic at the National Center of Maternal and Child Health (NCMCH) with an eight-year history of primary infertility. Clinical examination showed a normal intelligence with a coarse facial appearance and small testicles. Hormonal tests detected elevated levels of prolactin (PRL), follicle stimulating hormone (FSH), and luteinizing hormone (LH), and low levels of testosterone. Chromosomal analysis with fluorescence in situ hybridization (FISH) revealed a 46XX with SRY (sex-determining region Y) positive karyotype with translocation of the SRY gene (46XX der(X)t(X:Y)(p11.1:p11.3)(SRY+)). Magnetic resonance imaging (MRI) revealed bilateral seminal vesicles atrophy and agenesis of the vas deferens on the right side, which is rarely found in 46, XX male syndrome. Conclusion: Although 46XX testicular disorder of sexual development (DSD) cases are rare, multiple aspects of the clinical examinations are important to make an accurate diagnosis and to provide proper genetic counseling and guidance to patients in their long-term management.

Psychological Problem in Pediatric Disorder of Sex Development Patient and Relatives

Disorder of sexual development (DSD) is one of challenging disorder that has tobe done clinically and physiologically. The patients and relatives may experiencevarious psychosocial problems that have an impact on their live. The aim of thisstudy is to look at psychological problem in children with DSD and their relatives.A systematic search was conducted in PubMed for articles representinginformation on psychological problem to the patient and their relatives. Relevantdata were extracted and narratively reviewed. The result of this review can beused as basic data in the development of counselling program for the patientsand their relatives.

Swyer syndrome with malignant germ cell tumor: a case report

Background Swyer syndrome (Pure gonadal dysgenesis, 46 XY) is a rare form of disorder of sexual development. These patients presented with external female phenotype, normal Mullerian structures and streak gonads. Pure gonadal dysgenesis, XY patients are more likely to develop germ cell tumors due to the presence of the Y chromosome. Case presentation A 19-year-old patient with a female external phenotype presented with primary amenorrhea. Clinical examination, Karyotyping, imaging, and histopathological assessment revealed Swyer syndrome. On imaging, a right adnexal mass with calcification was detected. Laparoscopic surgery with histopathology revealed a malignant germ cell tumor. Conclusions Swyer syndrome represents a rare form of sexual development that necessitates a meticulous clinical, laboratory and radiological evaluation. Clinically, the patients have a female external phenotype with 46xy Karyotyping. Imaging, Ultrasound is the primary imaging modality Imaging and MRI helps in detection of the exact site of streak gonads and characterization of lesions. CT is useful in detecting calcification, which is a hallmark in the diagnosis of gonadoblastoma. Early diagnosis of Swyer syndrome is crucial as prophylactic gonadectomy in these cases reduces the risk of developing germ cell tumors.

Psychological Problem in Pediatric Disorder of Sex Development Patient and Relatives

Disorder of sexual development (DSD) is one of challenging disorder that has to be done clinically and physiologically. The patients and relatives may experience various psychosocial problems that have an impact on their live. The aim of this study is to look at psychological problem in children with DSD and their relatives. A systematic search was conducted in PubMed for articles representing information on psychological problem to the patient and their relatives. Relevant data were extracted and narratively reviewed. The result of this review can be used as basic data in the development of counselling program for the patients and their relatives.

46, XY Disorder of Sexual Development with Ambiguous Female External Genitalia: A Case Report

Disorder of Sexual Development (DSD) is a group of congenital conditions with atypical development of sex at chromosomal, gonadal or anatomic level. Genetic males with DSD (46 XY DSD) can present with female external genital phenotype, ambiguous, or a micropenis. It is caused by incomplete intrauterine masculinization with or without the presence of Müllerian structures. It results either from decreased synthesis of testosterone or DHT or from impairment of androgen action. Herein, we report a case of a 13-year child raised as female with hoarseness of voice and gradual enlargement of clitoris with hormonal assessment not suggestive of either 5 Alfa Reductase deficiency, Congenital Adrenal Insufficiency Syndrome or 17β-Hydroxysteroid Dehydrogenase deficiency

Evaluation of Enzymatic Activity of Various HSD17B3 Mutants Using Androgen Receptor-Mediated Transactivation

17β-Hydroxysteroid dehydrogenases (17β-HSDs, HSD17B) catalyze the reduction of 17-ketosteroids and the oxidation of 17β-hydroxysteroids to regulate the production of sex steroids. Among HSD17B family, 17β-HSD type 3 (HSD17B3) is expressed in testicular Leydig cells and contributes to development of male sexual characteristics by converting androstenedione (A4) to testosterone (T). Mutations of HSD17B3 genes cause a 46,XY disorder of sexual development (46,XY DSD) as a result of low T production. Therefore, the evaluation of HSD17B3 enzymatic activity is important for understanding and diagnosing this disorder. Although various amino acid substitutions of HSD17B3 have been reported in previous studies, the enzymatic activities of these proteins were often not defined. This is probably due to the difficulties that such enzymatic activities have been evaluated by quantifying the conversion of A4 into T using radioactive isotopes and liquid chromatography-mass spectrometry-mass spectrometry (LC-MS/MS). We adapted a method that easily evaluates enzymatic activity of HSD17B3 proteins by quantifying the conversion from A4 to T using androgen receptor (AR)-mediated transactivation. HEK293 cells were transfected to express human HSD17B3, and incubated medium containing A4. Depending on the incubation time with HSD17B3-expressing cells, the culture media progressively increased luciferase activities in CV-1 cells, transfected with the AR expression vector and androgen-responsive reporter. These luciferase activities reflected T concentrations in culture media defined by LC-MS/MS. This system is also applicable to detect the conversion of A4 to T by HSD17B1 and HSD17B5. In addition, it can evaluate the conversion of 11-ketoandrostenedione to 11-ketotestosterone by HSD17B family. Establishment of HEK293 cells expressing various missense mutations in the HSD17B3 gene with (N74T, A188V, M197K, A200V,, V225M, H271R) or without (V31I, E67K and G289S) the manifestation of 46,XY DSD revealed that this system is effective to evaluate the enzymatic activities of mutant proteins. A188V, A200V, V225M and H271R mutations completely inactivated the enzymatic function. N74T and M197K mutations showed some residual activities. In contrast, V31I, E67K and G289S substitutions showed similar activities as the wild-type protein.

Disorder of Sexual Development Males With XYY in Blood Have Exactly X/XY/XYY Mosaicism in Gonad Tissues

Y chromosome represents masculinization. The extra Y chromosome of XYY patients usually leads to over-masculinization phenotypes. The occurrence of several DSD cases with XYY in blood is controversial. Is XYY associated with disorder of sex development (DSD)? What is the mechanism behind DSD in males with XYY in blood? To this end, this study retrospectively analyzed blood-karyotype data of 4,437 DSD male children and karyotypes data of 6,259 newborn males as the control. Exome sequencing (ES) was performed to test whether the patients with DSD and with XYY in blood had other variants on known DSD-genes. Testicular biopsy was performed. Fluorescence in situ hybridization (FISH) was used to test whether a sex chromosome mosaicism was present in the oral epithelial cells or gonad tissue of patients with DSD and with XYY in blood. Among 4,437 DSD males who received cytogenetic evaluation, 14 patients with 47,XYY were identified. By contrast, five individuals among the 6,259 controls had 47,XYY. XYY in blood is more frequent among males with DSD than in other males (p = 0.004). The XYY karyotypes were confirmed again by GTG-banding in blood samples and by FISH performed on oral epithelial cells. ES on seven XYY DSD patients was successfully performed, but results did not identify any pathogenic variant on 55 known DSD genes. Gonad biopsy (n = 3) revealed testicular dysplasia and true hermaphroditism. FISH of gonad tissues (n = 3) showed that all of the samples had mosaic for X/XY/XYY. This study is the first to investigate the relationship between XYY in blood and DSD. The knowledge that XYY is in the blood and in oral cells have X/XY/XYY mosaicism in gonadal tissue is new for both researchers and clinicians who seek to understand the genetic basis of DSD males.