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Swyer syndrome is a rare congenital condition that serves as a risk factor for developing germ cell tumors. The condition belongs to the group of 46, XY disorders of sexual development, is characterized by complete gonadal dysgenesis (CGD) and is mostly manifested as delayed puberty and primary amenorrhea during adolescence. Individuals with Swyer syndrome are known to be phenotypically female with normal internal and external female genitalia at birth. 46, XY GD involves a high risk of gonadoblastoma development with malignant potential such that the onset is greatest at or after the event of puberty. This report of a 12-year-old phenotypic female with 46, XY GD, who developed an advanced metastatic seminoma, highlights the rarity of the development of a seminoma in the context of 46, XY CGD. [ABSTRACT FROM AUTHOR]

Disorders of sex development (DSD) result from intrauterine defects in sex discrimination. The clinical phenotype differs based on the disease type. Cases with ambiguous external genitalia are diagnosed at birth. However, diagnosis of cases with normal-appearing external genitalia may be delayed until puberty. Here, we report a patient with a pelvic mass and a small uterus that was diagnosed by abdominal ultrasound, in addition to the history of primary amenorrhea and physical examination suggested Swyer syndrome, confirmed by genetic karyotyping. Pathological examination of the surgically removed mass revealed dysgerminoma. Until the age of 19, the patient did not have any idea about 46, XY karyotype, and assumed to be a female. The development of dysgerminoma (as a result of the simultaneous presence of gonadal dysgenesis and Y-chromosome) was another challenge that the patient had to deal with. The diagnosis of this patient at an earlier age could have prevented the development of gonadoblastoma, by removal of the streak gonads. By the presentation of this case, we intend to increase the physician's awareness about DSDs; earlier diagnosis may help the patient deal with her disease better and reduce the risk of further complications. [ABSTRACT FROM AUTHOR]

The fertility of sex-reversed XY female mice is severely impaired by a massive loss of oocytes and failure of meiotic progression. This phenomenon remains an outstanding mystery. We sought to determine the molecular etiology of XY oocyte dysfunction by generating sex-reversed females that bear genetic ablation of Sry, a vital sex determination gene, on an inbred C57BL/6 background. These mutant mice, termed XYsry- mutants, showed severe attrition of germ cells during fetal development, resulting in the depletion of ovarian germ cells prior to sexual maturation. Comprehensive transcriptome analyses of primordial germ cells (PGCs) and postnatal oocytes demonstrated that XYsry- females had deviated significantly from normal developmental processes during the stages of mitotic proliferation. The impaired proliferation of XYsry- PGCs was associated with aberrant β-catenin signaling and the excessive expression of transposable elements. Upon entry to the meiotic stage, XYsry- oocytes demonstrated extensive defects, including the impairment of crossover formation, the failure of primordial follicle maintenance, and no capacity for embryo development. Together, these results suggest potential molecular causes for germ cell disruption in sex-reversed female mice, thereby providing insights into disorders of sex differentiation in humans, such as "Swyer syndrome," in which patients with an XY karyotype present as typical females and are infertile.

Context: 46,XY, disorders of sexual development (46,XY, DSD) is a congenital genetic disease whose pathogenesis is complex and clinical manifestations are diverse. The existing molecular research has often focused on single-centre sequencing data, instead of prediction based on big data. Aims: This work aimed to fully understand the pathogenesis of 46,XY, DSD, and summarise the key pathogenic genes. Methods: Firstly, the potential pathogenic genes were identified from public data. Secondly, bioinformatics was used to predict pathogenic genes, including hub gene analysis, protein–protein interaction (PPI) and function enrichment analysis. Lastly, the genomic DNA from two unrelated families were recruited, next-generation sequencing and Sanger sequencing were performed to verify the hub genes. Key results: A total of 161 potential pathogenic genes were selected from MGI and PubMed gene sets. The PPI network was built which included 144 nodes and 194 edges. MCODE 4 was selected from PPI which scored the most significant P -value. The top 15 hub genes were ranked and identified by Cytoscape. Furthermore, three variants were found on SRD5A2 gene by genome sequencing, which belonged to the prediction hub genes. Conclusions: Our results indicate that occurrence of 46,XY, DSD is attributed to a variety of genes. Bioinformatics analysis can help us predict the hub genes and find the most core network MCODE model. Implications: Bioinformatic predictions may provide a novel perspective on better understanding the pathogenesis of 46,XY, DSD. 46,XY, disorders of sexual development (46,XY, DSD) is a congenital genetic disease. The existing molecular research has focused on single-centre sequencing data, instead of prediction based on big data. In this study, the relevant pathogenic genes are predicted by bioinformatics, and verified by gene sequencing technology. Our results indicate that occurrence of 46,XY, DSD is attributed to a variety of genes. Bioinformatics analysis can help us predict the hub genes and find the most core network MCODE model. [ABSTRACT FROM AUTHOR]

Background: We presented the clinical and genetic features of a male ambiguity due to 17-beta-hydroxysteroid dehydrogenase 3 (17B-HSD3) deficiency. Methods: The proposita was an 11-year-old girl and the first child of a consanguineous family. The external genitalia were completely female and had a short vaginal pouch. She had palpable gonads in her inguinal area and underwent bilateral gonadectomy at the age of two. At the age of 10, she was referred to our clinic for more evaluation. In pelvic sonography, uterine and ovarian were not seen. Her karyotype was 46, XY, and her LH and FSH levels were elevated, and three of the patient’s aunts and one of the mother’s aunts had similar signs. Conclusions: We identified a novel homozygous missense variation (c.731T>A, p. Ile244Lys) in the HSD17B3 gene. This alteration changes Isoleucine to Lysine in exon 10.

SOX8 is an HMG-box transcription factor closely related to SRY and SOX9. Deletion of the gene encoding Sox8 in mice causes reproductive dysfunction but the role of SOX8 in humans is unknown. Here, we show that SOX8 is expressed in the somatic cells of the early developing gonad in the human and influences human sex determination. We identified two individuals with 46, XY disorders/differences in sex development (DSD) and chromosomal rearrangements encompassing the SOX8 locus and a third individual with 46, XY DSD and a missense mutation in the HMG-box of SOX8. In vitro functional assays indicate that this mutation alters the biological activity of the protein. As an emerging body of evidence suggests that DSDs and infertility can have common etiologies, we also analysed SOX8 in a cohort of infertile men (n = 274) and two independent cohorts of women with primary ovarian insufficiency (POI; n = 153 and n = 104). SOX8 mutations were found at increased frequency in oligozoospermic men (3.5%; P

BACKGROUND:Disorders of sex development (DSD) have an estimated frequency of 0.5% of live births encompassing a variety of urogenital anomalies ranging from mild hypospadias to a discrepancy between sex chromosomes and external genitalia. In order to identify the underlying genetic etiology, we had performed exome sequencing in a subset of DSD cases with 46,XY karyotype and were able to identify the causative genetic variant in 35% of cases. While the genetic etiology was not ascertained in more than half of the cases, a large number of variants of unknown clinical significance (VUS) were identified in those exomes. METHODS:To investigate the relevance of these VUS in regards to the patient's phenotype, we utilized a mouse model in which the presence of a Y chromosome from the poschiavinus strain (Y POS ) on a C57BL/6J (B6) background results in XY undervirilization and sex reversal, a phenotype characteristic to a large subset of human 46,XY DSD cases. We assessed gene expression differences between B6-Y B6 and undervirilized B6-Y POS gonads at E11.5 and identified 515 differentially expressed genes (308 underexpressed and 207 overexpressed in B6-Y POS males). RESULTS:We identified 15 novel candidate genes potentially involved in 46,XY DSD pathogenesis by filtering the list of human VUS-carrying genes provided by exome sequencing with the list of differentially expressed genes from B6-Y POS mouse model. Additionally, we identified that 7 of the 15 candidate genes were significantly underexpressed in the XY gonads of mice with suppressed Sox9 expression in Sertoli cells suggesting that some of the candidate genes may be downstream of a well-known sex determining gene, Sox9. CONCLUSION:The use of a DSD-specific animal model improves variant interpretation by correlating human sequence variants with transcriptome variation.

Investigation of disorders of sex development (DSD) has resulted in the discovery of multiple sex-determining genes. MAP3K1 encodes a signal transduction regulator in the sex determination pathway and is emerging as one of the more common genes responsible for 46,XY DSD presenting as complete or partial gonadal dysgenesis. Clinical assessment, endocrine evaluation, and genetic analysis were performed in six individuals from four unrelated families with 46,XY DSD. All six individuals were found to have likely pathogenic MAP3K1 variants. Three of these individuals presented with complete gonadal dysgenesis, characterized by bilateral streak gonads with typical internal and external female genitalia, while the other three presented with partial gonadal dysgenesis, characterized by incomplete testicular development, resulting in clitoral hypertrophy with otherwise typical female external genitalia. Testing for MAP3K1 variants should be considered in patients with 46,XY complete or partial gonadal dysgenesis, particularly in families with multiple members affected with 46,XY DSD. Identification of a MAP3K1 variant should prompt an evaluation for DSD in female siblings of the proband.

Cell lineages of the early human gonad commit to one of the two mutually antagonistic organogenetic fates, the testis or the ovary. Some individuals with a 46,XX karyotype develop testes or ovotestes (testicular or ovotesticular disorder of sex development; TDSD/OTDSD), due to the presence of the testis-determining gene, SRY Other rare complex syndromic forms of TDSD/OTDSD are associated with mutations in pro-ovarian genes that repress testis development (e.g. WNT4); however, the genetic cause of the more common non-syndromic forms is unknown. Steroidogenic factor-1 (known as NR5A1) is a key regulator of reproductive development and function. Loss-of-function changes in NR5A1 in 46,XY individuals are associated with a spectrum of phenotypes in humans ranging from a lack of testis formation to male infertility. Mutations in NR5A1 in 46,XX women are associated with primary ovarian insufficiency, which includes a lack of ovary formation, primary and secondary amenorrhoea as well as early menopause. Here, we show that a specific recurrent heterozygous missense mutation (p.Arg92Trp) in the accessory DNA-binding region of NR5A1 is associated with variable degree of testis development in 46,XX children and adults from four unrelated families. Remarkably, in one family a sibling raised as a girl and carrying this NR5A1 mutation was found to have a 46,XY karyotype with partial testicular dysgenesis. These unique findings highlight how a specific variant in a developmental transcription factor can switch organ fate from the ovary to testis in mammals and represents the first missense mutation causing isolated, non-syndromic 46,XX testicular/ovotesticular DSD in humans.

PurposeWe examined the psychosocial characteristics of parents of children with disorders of sex development at early presentation to a disorders of sex development clinic. Parental anxiety, depression, quality of life, illness uncertainty and posttraumatic stress symptoms were assessed. Additionally we evaluated the relationship of assigned child gender to parental outcomes.Materials and methodsA total of 51 parents of children with ambiguous or atypical genitalia were recruited from 7 centers specializing in treatment of disorders of sex development. At initial assessment no child had undergone genitoplasty. Parents completed the Cosmetic Appearance Rating Scale, Beck Anxiety Inventory, Beck Depression Inventory, SF-36, Parent Perception of Uncertainty Scale and Impact of Event Scale-Revised.ResultsA large percentage of parents (54.5%) were dissatisfied with the genital appearance of their child, and a small but significant percentage reported symptoms of anxiety, depression, diminished quality of life, uncertainty and posttraumatic stress. Few gender differences emerged.ConclusionsAlthough many parents function well, a subset experience significant psychological distress around the time of diagnosis of a disorder of sex development in their child. Early screening to assess the need for psychosocial interventions is warranted.

Androgen insensitivity syndrome (AIS) is a congenital disorder in which a defect in the androgen receptor (AR) gene leads to cellular resistance to androgens. Defects in the AR gene, located on the X chromosome, result in the development of a feminine phenotype in chromosomally male (46, XY) individuals. In this case report, we present a 44 years old patient with complete androgen insensitivity syndrome (CAIS) initially presenting with primary amenorrhea. The patient underwent a full clinical evaluation, revealing hypoplastic vagina and a lack of uterus and ovaries. Hormonal evaluation revealed markedly elevated testosterone, FSH, and LH serum concentrations. Diagnostic imaging, including pelvic MRI, confirmed the presence of two solid masses in the inguinal canals (right 26 × 13 mm, left 25 × 15 mm). The patient underwent genetic testing, revealing a 46 XY karyotype and an as of yet unprecedented androgen receptor mutation. The type of the mutation was a single-base exchange – the substitution from cytosine to thymine in chromosome X:66942710 position (referred to human reference genome GRCh37), which has resulted in an amino acid changes from leucine (CTT) to phenyloalanine (TTT) in ligand-binding domain. [ABSTRACT FROM AUTHOR]

This is the first case report in Oman and the Gulf region of a 17-β-hydroxysteroid dehydrogenase type 3 (17-β-HSD3) deficiency with a novel mutation in the HSD17B3 gene that has not been previously described in the medical literature. An Omani child was diagnosed with 17-β-HSD3 deficiency and was followed up for 11 years at the Pediatric Endocrinology Clinic, Royal Hospital, Oman. He presented at the age of six weeks with ambiguous genitalia, stretched penile and bilateral undescended testes. Ultrasound showed no evidence of any uterine or ovarian structures with oval shaped solid structures in both inguinal regions that were confirmed by histology to be testicular tissues with immature seminiferous tubules only. The diagnosis was made by demonstrating low serum testosterone and high androstenedione, estrone, and androstenedione:testosterone ratio. Karyotyping confirmed 46,XY and the infant was raised as male. Testosterone injections (25mg once monthly) were given at two and six months and then three months before his surgeries at five and seven years of age when he underwent multiple operations for orchidopexy and hypospadias correction. At the age of 10 years he developed bilateral gynecomastia (stage 4). Laboratory investigations showed raised follicle-stimulating hormone, luteinizing hormone, androstenedione, and estrone with low-normal testosterone and low androstendiol glucurunide. Testosterone injections (50mg once monthly for six months) were given that resulted in significant reduction in his gynecomastia. Molecular analysis revealed a previously unreported homozygous variant in exon eight of the HSD17B3 gene (NM_000197.1:c.576G>A.Trp192*). This variant creates a premature stop codon, which is very likely to result in a truncated protein or loss of protein production. This is the first report in the medical literature of this novel HSD17B3 gene mutation. A literature review was conducted to identify the previous studies related to this disorder.

Y-chromosome gonadal dysgenesis (GD) is a rare subgroup of disorders of sexual development (DSD) which results from underdeveloped testis and may exhibit heterogenous symptoms. These patients are phenotypically classified into two groups - complete and partial, and their karyotypic description is either 46,XY GD or 45,X/46,XY GD. In this study; we aimed to evaluate the characteristics of cases with Y-chromosome GD. Methods: Thirty eight cases were followed-up between 1998 and 2016. The age of admission ranged between 0 and 17 years. Clinical and laboratory findings as well as follow-up characteristics of the cases were evaluated retrospectively from the patient files. Results: There were 26 cases (four complete, 22 partial) in the 46,XY GD group, and 12 cases (four complete, 8 patients with complete GD in the 45,X/46,XY. Mean age at admission was 6.2±4.6 years for all cases. Patients with complete GD in the 45,X/46,XY GD group were diagnosed earlier that the patients with complete GD in the 46,XY group [11 years vs. 14.31 years of age (p<0.01)]. There were no additional findings in 55% of all patients. In the remaining 45% additional clinical findings, mainly short stature, were detected in 75% of the patients in the 45,X/46,XY GD and 30% of the patients in the 46,XY GD groups. All patients with complete 46,XY and 45,X/46,XY GD were raised as females. There was no gender dysphoria in patients that were raised as females, except for one case. Gonadectomy was performed in 14 patients, at a mean age of 8.75±2.3 years and pathological assessment of the gonads was reported as normal in all cases. Conclusion: Y-chromosome GD is a very heterogenous clinical and genetic disorder and requires a multifaceted approach to management. Whether including syndromic features or not, associated clinical features may lead to earlier diagnosis, especially in complete forms of GD. Due to difficulties encountered in the long-term follow-up of these patients, evaluation of appropriateness of sex of rearing decision is not truly possible. Performance of gonadectomy during the first decade appears be a preventive factor for tumor development since these tumors are usually seen during the second decade [ABSTRACT FROM AUTHOR]

OBJETIVO: verificar a prevalência e as características clínicas de pacientes com amenorréia primária e cariótipo XY avaliadas em nosso Serviço com o intuito de identificar achados que possam auxiliar em seu reconhecimento. MÉTODOS: no período de Janeiro de 1975 a Novembro de 2007, foram avaliadas 104 pacientes com amenorréia primária. Para todos os casos foi realizada a análise pelo cariótipo por bandas GTG. Destas, 21 (20,2%) apresentavam uma constituição 46,XY. Contudo, duas foram excluídas do estudo por terem prontuários incompletos. Das 19 pacientes que compuseram a amostra, a maior parte veio encaminhada pela ginecologia (63,2%). Suas idades variaram entre 16 e 41 anos (média de 22,1 anos). Realizou-se uma coleta de dados sobre sua história familiar e pregressa, exame físico e resultados de exames complementares. Para determinação dos seus diagnósticos levaram-se em consideração essas informações. RESULTADOS: a síndrome de resistência aos androgênios foi o diagnóstico predominante (n=12; 63,2%). Cinco pacientes (26,3%) apresentavam disgenesia gonadal pura XY (DGP XY), uma (5,3%) deficiência de 17-alfa hidroxilase e uma (5,3%) deficiência de 5-alfa redutase. Achados clínicos freqüentemente observados nessas pacientes incluíram desenvolvimento anormal dos caracteres sexuais secundários (n=19), agenesia uterina com vagina em fundo de saco (n=14), história familiar de amenorréia (n=8) e gônadas palpáveis no canal inguinal (n=5). Duas delas apresentavam história de hérnia inguinal. Hipertensão arterial sistêmica foi diagnosticada somente na paciente com deficiência de 17-alfa hidroxilase, e malignização gonadal, naquela com DGP XY. CONCLUSÕES: a freqüência de pacientes com cariótipo XY (20%) foi superior à usualmente descrita na literatura (3 a 11%). Acreditamos que isso tenha relação com a forma de encaminhamento das pacientes ao Serviço. Certos achados da história clínica e do exame físico deveriam ser rotineiramente avaliados em indivíduos com amenorréia primária. Dessa forma, haveria um reconhecimento mais precoce das pacientes 46,XY e, conseqüentemente, um adequado manejo clínico das mesmas.PURPOSE: to verify the prevalence and clinical characteristics of patients with primary amenorrhea and XY caryotype, evaluated in our Service, aiming at identifying findings which could help their recognition. METHODS: from January 1975 to November 2007, 104 patients with amenorrhea were evaluated. All the cases were analyzed by the caryotype by GTG bands. Among them, 21 (20.2%) presented a XY 46 constitution. Nevertheless, two of them were excluded from the study, because of incomplete data in their patient's chart. Most of the 19 patients who formed the sample had been referred to us by the gynecology clinics (63.2%). Their ages varied from 16 to 41 years old (an average of 22.1). Data were collected about their family and previous history, physical examination and results of complementary exams and the information was taken into consideration to determine the diagnosis. RESULTS: the predominant diagnosis was resistance to androgens syndrome (n=12; 63.2%); five patients (25.3%) presented XY pure gonadal dysgenesis (XY PGD), one (5.3%) 17 alpha-hydroxylase deficiency, and one (5.3%), 5 alpha-reductase deficiency. Clinical findings frequently found in these patients included abnormal development of secondary sexual characters (n=19), uterine agenesia with a blind vagina (n=14), family history of amenorrhea (n=8), and palpable gonads in the inguinal canal (n=5). Two of them presented a history of inguinal hernia. Systemic arterial hypertension was only diagnosed in the patient with 17 alpha-hydroxylase deficiency, and gonadal malignization, in the one with XY PGD. CONCLUSIONS: the rate of patients with XY caryotype (20%) was higher than the one described in the literature (3 to 11%). It is believed that this fact is related to the way patients are usually referred to our service. Some findings from the clinical history and from the physical examination should be evaluated as a routine in individuals with primary amenorrhea. This way, there would be a more precocious detection of XY 46 patients, and a better clinical management of them, as a consequence.

In this study, cytogenetic and clinic findings of 46,X,i(Xq) and 45,X/46,X,i(Xq) which are the rare types of Turner syndrome are evaluated. Two patients were directed to the Cytogenetic Laboratory from Gynecology Clinic with chromosomal anomaly indication. Their peripheric blood samples are analyzed karyotypically using Giemsa-Tripsin Bantama method. Case 1. The patient is 17 years old, has short height, a low-posterior hairline, short neck, small and wide apart breasts, normal external genitals and underdeveloped internal genitals. Her karyotype was 45,X/46,X,i(Xq). Case 2. The patient is 19 years old, has primer amenore, short height, a low-posterior hairline, wide apart and underdeveloped breasts, normal external genitals, underdeveloped uterus, obscure ovarium. Her karyotype was determined to be 46,X,i(Xq). Although symptoms progress slightly weaker, our 45,X/46,X,i(Xq) and 46,X,i(Xq) cases, which are rare types of Turner Syndrome, are generally consistent with phenotypic findings of Turner syndrome. [ABSTRACT FROM AUTHOR]

Testicular Regression Syndrome (TRS) is defined as the absence or an incomplete development of the testis of varying degrees in 46XY patients with normal external genitalia. The prevalence ranges from 3-20% of cases previously diagnosed as cryptorchidism. We report the case of a 7-year-old boy who underwent surgical exploration with an initial diagnosis of cryptorchidism. Testicular structure was not identified and presumed testicular remnants were sent for histological analysis. The histological sections showed a fibrovascular nodule, structures of the spermatic cord and calcification, supporting the diagnosis of TRS

The case of a girl born with a disorder of sexual differentiation has been described. At the newborn age the child was assigned to the female sex only on the basis of greater macroscopic resemblance of external genitals. The clitoris was growing with the child and at the age of 6 years the size reached 3 cm and protruded from the labia. That was the reason why the family decided to visit a doctor. The genetic examination revealed karyotype 46 XY. In the course of the subsequent more than two years, various specialists were attended for establishment of diagnosis and therapy. As late as at the age of 8.5 years, the helpless mother decided to come for a consultation to endocrinology out-patient of 2nd Children Clinic, Medical Faculty and Children Faculty Hospital in Bratislava. The child was then hospitalized for solution of the condition. MR imaging revealed the rudimentary male internal organs were present, whereas the female counterpart was not. Laboratory examinations were within normal limits for the given age. Under the present conditions it was not possible to establish final diagnosis. In view of the age, upbringing to a female direction and girl's behavior and feelings, and considering the parents' desire, the patient was left with the female sex. The inguinal tissues (susp. testes) were extirpated and histological findings revealed hypoplastic testes without Leydig cells. The external genitals of the patient were adjusted to the female direction. [ABSTRACT FROM AUTHOR]

Objective:To investigate the complete androgen insensitivity syndrome (CAIS), and evaluate the application of laparoscopy in the diagnosis and treatment in CAIS. Methods：Four cases of CAIS admitted to and underwent surgeiy in General Gynecology in Tianjin Central Hospital of Gynecology and Obstetrics from September of 2009 to October of 2012 were studied retrospectively, through analyzing and comparing medical histoiy, clinical characteristics, hormone levels [testosterone, estradiol (E2), luteinizing hormone (LH), follicle stimulating hormone (FSH), progesterone, prolactin (PRL) etc.], surgical findings and gonad pathological results were analysed combined with literatures. Results： All patients had a kaiyotype of 46, XY. Hormone levels were measured, compared with normal males, three cases had normal testosterone, one was significantly lower than the normal, four cases had elevated LH, FSH was normal in one case but higher than normal in other three cases, one in which was significantly higher than the normal; E2, progesterone, PRL were normal in four cases. One case underwent laparoscopic bilateral orchiectomy, one case underwent laparoscopic bilateral orchiectomy and perineal vaginoplasty, one case underwent bilateral orchiectomy by vulva, one case underwent laparoscopic assisted bilateral orchiectomy by inguinal. Four cases of pathologically proven after excision of the gonads were dysplasia of testicular tissue. Conclusions ： Early diagnosis of CAIS is veiy important, patients should be treated as female social gender with gonadectomy and subsequent hormone replacement. Laparoscopy has unique advantages in the diagnosis and treatment of CAIS. [ABSTRACT FROM AUTHOR]

Disorders of sex development (DSD) constitutes a group of congenital conditions that affect urogenital differentiation and are associated with chromosomal, gonadal and phenotypic sex abnormalities. To evaluate the clinical and genetic features of childhood DSD cases. DSD patients followed up between the years of 2002–2018 were evaluated in terms of their complaints, demographic, clinical features and genetic diagnoses. Out of 289 patients, 143(49.5%) were classified as 46XY DSD, 62(21.5%) as 46XX DSD and 84(29%) as sex chromosomal DSD. Genetic diagnosis was achieved in 150 patients (51.9%). The distribution of the molecular diagnosis of the 46XY DSD patients were; 12 (26.6%) SRD5A2 , 10 (22.2%) AR , 7 (15.5%) HSD17B3 , 3 (6.6%) WT-1 , 2 (4.4%) AMHR2 , 2 (4.4%) AMH , 2 (4.4%) LHCGR , 2 (4.4%) HSD3B2 , 1 (2.2%) NR5A1 , 1 (2.2%) CYP17A1 and 1 (2.2%) SRY mutation. Fifty (80.6%) of the 46XX DSD patients received a diagnosis with clinical and laboratory findings. Twenty-four (38.7%) of them were 21-hydroxylase deficiency, 9(14.5%) Rokitansky-Küster-Hauser Syndrome, 4 (6.5%) 11-β hydroxylase deficiency, 3 (4.8%) gonadal dysgenesis and 2 (3.2%) aromatase deficiency. In 46XX group pathogenic mutations were detected in 21(33.8%) of the patients. Eighty-four (29%) patients were diagnosed as sex chromosomal disorder. Of these 66 (78.5%) were Turner Syndrome, 6 (7.2%) Klinefelter Syndrome and 10 (11.9%) mix gonadal dysgenesis. Gender re-assignment was decided in 11 patients. Malignant and pre-invasive lesions was diagnosed in 8 (2.7%) patients. Many of DSD's are clinically similar and etiology of numerous of them still cannot be established. A multi-disciplinary approach and new rapid genetic diagnostic methods are needed in the process from diagnosis to gender assignment and follow-up. • Disorders of sex development (DSD) are still not fully clarified. • Still DSD management is difficult for many clinicians and geneticists, and it is a stress factor for the family. • This study clarifies clinical and genetical characteristics of many DSDs and will guide clinicians in diagnosis and follow-up. [ABSTRACT FROM AUTHOR]

46,XY disorder of sex development (46,XY DSD) is characterized by a 46,XY karyotype, ambiguous genitalia with mild to severe penoscrotal hypospadias ,dysgenetic testes, reduced to no sperm production, and müllerian structures that range from absent to presence of a fully developed uterus and fallopian tubes. 46,XY complete gonadal dysgenesis is characterized by a 46,XY karyo­type, normal female external genitalia, completely undeveloped streak gonads, no sperm production, and presence of normal müllerian structures and often not diagnosed until puberty when secondary sexual characteristics fail to develop. The diagnosis of 46,XY DSD and 46,XY gonodal dysgenesis relies on clinical findings, gonadal histology, chromosome analysis testing to detect changes in genes.Because of increased risk for gonadal tumors(most commonly dysgerminoma) abdominal streak gonads should be surgically removed . Typically, hormone replacement therapy (HRT) is required from puberty onward. Here we describe the clini­cal, endocrinological and molecular data of a patient with complete 46, XY gonadal dysgenesis. [ABSTRACT FROM AUTHOR]

Objective: To report a case of successful pregnancy in a patient with 46,XY karyotype with primary ovarian failure.Design: Case report.Setting: Fertility Research Center, G.G. Hospital, Chennai, Tamil Nadu, India.Patient(s): A 27-year-old woman with hypoplastic uterus, normal fallopian tubes on both sides, and gonadal dysgenesis.Intervention(s): Chromosomal analysis, diagnostic laparoscopy, donor oocyte program, gamete intrafallopian transfer, and gonadectomy.Main Outcome Measure(s): Response to hormone replacement therapy and the probability of achieving a pregnancy by a tubal procedure.Result(s): Treatment was successful, and the patient delivered a live baby.Conclusion(s): A hypoplastic uterus of patients with the 46,XY karyotype can be stimulated by the use of cyclical steroid therapy to accommodate pregnancy and facilitate tubal procedures in patients with normal fallopian tubes. [ABSTRACT FROM AUTHOR]