True Hermaphroditism Research Articles

Ovotesticular Disorder of Sex Development: A Rare Case of Lateral Subtype 45X/46XY kariotype Diagnosed in Adulthood

A 53-year-old male referred to our centre because of hypergonadotropic hypogonadism detected during urological follow-up for urethral lithiasis. Physical examination showed short stature, micropenis, ambiguous external genitalia, and normal secondary sexual characteristics. Karyotype: 45 × 0/46XY. Abdominal MRI revealed the presence of uterus-like structure, right annex, and left testes without prostate. He underwent laparoscopic removal of dysgenetic tissues; histologic examination confirmed the presence of little uterus, fallopian tubes, little atrophic ovary, and vaginal tract; left testes was atrophic with sclero-jalinosis of seminal tubes and Leydig's cells hyperplasia. Testosterone replacement therapy was started after surgery and prostate became MRI visible after 2 years.

SUN-208 Rare Case of 47XXY/46XX Mosaic Klinefelter Syndrome

Introduction: Klinefelter syndrome (KS) is the most common X chromosome abnormality and genetic cause of male infertility. Nondisjunction of paired X chromosomes during meiosis or gametogenesis gives rise to the karyotype 47XXY seen in 80 % of cases. The most common form of mosaicism results from post-fertilization nondisjunction of the XXY zygote in two cell lines 47XXY/46XY in 15-20 % of KS. The 47XXY/46XX mosaic form is very rare with only 20-25 cases described in the literature to date. Phenotype varies with distribution of the two cell lineages in developing embryo tissues, including KS male, true hermaphroditism, ovarian hypoplasia and normal female. Only 10 cases have been reported of 47XXY/46XX mosaic KS male phenotype . Our case is the 11th. Case: A 39 year old male presented with fatigue, weight gain, poor concentration and loss of libido. He reported no secondary sexual development during puberty, including hair, muscle mass, penis and testicles, and minimal erections. On exam, both testes were less than 2 cm with a normal penis. He had abdominal obesity, reduced muscle mass, and gynecomastia, as well as male pattern frontal baldness. Total testosterone (T) was 125 ng/dl (250-1100), Free T was 16 ng/dl (46-224), albumin was 3.9, FSH was 25 mIU/ml, and LH was 15.9 mIU/ml. Chromosome analysis: 25/30 (83%) cells 47XXY and 5/30 (17 %) cells 46XX. FISH study on 100 peripheral blood cells showed 87 % 47XXY and 14 % 46XX. The patient did not desire fertility and started testosterone replacement. Conclusion: Our case demonstrated the common features of 47XXY/46XX mosaic KS, including small testes, gynecomastia, hypergondotropic hypogonadism, and normal IQ. Interestingly, our patient had male pattern baldness, which was also common in his family. The average age of diagnosis for cases reported to date was 12-62 years, similar to ours, suggesting a delay in diagnosis, as can occur in many KS cases. Distribution of cell lines can vary between different tissues, but the presence of a Y chromosome in the gonad determines the phenotype. Mediastinal germ cell tumor, testicular teratoma, and radioulnar synostosis have been noted in 3 cases but not in this case. Mosaic cases tend to be more androgenic, and are more likely to have spermatogenesis than non-mosaic KS. This along with the failure to detect the 46XX cell line in routine blood cytogenetic tests (as opposed to gonadal tissue) is the reason for delayed detection in many cases. KS mosaicism should be considered in all cases of male infertility.

SAT-301 Mixed Gonadal Dysgenesis: A Case Report

INTRODUCTION: An ambiguous genitalia is a birth defect of the sex organs that makes it unclear whether an affected newborn is a girl or a boy. This condition occurs approximately 1 in every 4,500 births. Defects of the external genital organs (penis, testes, or clitoris) usually result from abnormal levels of sex hormones in the fetus before birth. Here we present a case report of an 18year old girl with ambiguous genitalia. CLINICAL CASE: An 18-year-old girl presented with complaints of primary amenorrhea along with lack of secondary sexual characters. Her mother also gave history of genital ambiguity. No history of recent change in sexual identity. Past history, family history, antenatal history, perinatal history and developmental history were non contributory. On examination, anthropometric measurements were appropriate for her age. She was normotensive. General and systemic examination were unremarkable and there were no Turner stigmata. Genital examination revealed phallic structure of 5cm length and two seperate perineal openings. Minimal posterior fusion of labial margins and a palpable mass were noted in left inguinal region. Prader staging was 3/5. Sexual maturity rating was A0P1B2. Her basal serum cortisol 14.53μg/dL,[5-25μg/dL], 17-OH-progesterone (17-OHP) 1.51ng/mL,[0.09-2.19ng/ml] and serum estradiol level 37 pg/ml [13.6-54.4pg/ml] were normal while basal androstenedione 2.23 ng/ml[0.29-1.44 ng/ml], serum testosterone 1ng/mL [ lt 0.6ng/ml]and gonadotrophins Pooled LH 22 IU/L [5-15IU/ml] and FSH 76.37 IU/L [5-20IU/ml] were elevated. Karyotype analysis was 46XY. MRI pelvis revealed absent mullerian structures and ovaries, presence of seminal vesicle and left inguinal subcutaneous sac, containing gonad, suggestive of testis was noted. Intra abdominal right gonad was detected on diagnostic laparoscopy. No vas deferens noted in entire deep inguinal ring. Left gonad noted in its entirety in left deep inguinal ring. Rudimentary uterus was also noted. Histopathological examination of gonadal biopsy revealed presence of testicular tissue showing atrophic seminiferous tubules with hyperplasia of Leydig cells. No ovarian tissue was seen. Based on these results a diagnosis of 46XY mixed gonadal dysgenesis was made, which is rare and is difficult to distinguish from 46XY ovotesticular disorder of sexual differentiation. The patient underwent feminizing genitopasty after discussion with the patient’s caregivers. CONCLUSION: Mixed Gonadal Dysgenesis represents an intermediate between pure gonadal dysgenesis and ovotesticular disorder of sexual differentiation (DSD). The external genitalia, internal genitalia, and gonadal phenotype are highly variable. The most common genotype in these patients is 46XO/XX, however 46XY genotype has also been described, which can be difficult to distinguish from 46XY ovotesticular DSD.

Outcome of feminizing genital reconstruction in female sex assigned disorder of sex development in a low-income country

In patients with disorders of sex development (DSD), surgical/medical treatments are undertaken after sex assignment to ensure congruent bodily appearance and function. Genital reconstruction in these patients can be daunting with varied outcome. Understanding these outcomes is imperative, more especially in a developing country where added challenges exist. This study evaluates the outcome of genital surgery in patients with DSD assigned female sex. A retrospective analysis of 25 cases of female sex assigned DSD managed in two tertiary centers in southeast Nigeria was performed. Data of these cases were collected from the case notes, discharge summaries, and theater records. IBM SPSS Statistics Data Editor, version 21, was used for data entry and analysis. The patients presented at median age of 12 months (range 2 days-30 years), with 15 (60%) cases reared as female and 10 (40%) reared as male before presentation. The predominant phenotype was phallus with empty fused/unfused labioscrotum and urethra opening in the labioscrotum or perineum in 21 (84%) patients. Evaluation revealed features suggestive of 46XX DSD in 21 (84%) patients, ovotesticular DSD in two (8%), and androgen insensitivity in two (8%). A total of 10 cases required sex reassignment after evaluation. Overall, 24 of the 25 cases had feminizing genital procedures. After a median follow-up period of 2 years (range 2 months-8 years), six (25%) cases developed procedure-related complications, three (12.5%) had social maladjustment, and two (8.3%) patients reported features of gender dysphoria. The procedures of feminizing genitoplasty in this study did not differ from the established procedure. However, as a result of challenges of delayed presentation, inadequate early management, sociocultural factors, and a lack of facilities for full evaluation, some cases may require sex reassignment and more daunting reconstructive procedures. This may give rise to less than optimal outcome. The study was limited by the retrospective nature, small number of cases, and the short duration of follow-up of the cases. Feminizing genital procedures for DSD in our setting may be associated with procedure-related complications and non-surgical complications. Improving surgical techniqueand addressing the challenges of delayed presentation and fixation on male gender may improve overall outcome.

Variant analysis of the chromodomain helicase DNA‐binding protein 7 in pediatric disorders of sex development

ImportanceThis study investigated the role of the chromodomain helicase DNA‐binding protein 7 (CHD7) in disorders of sex development (DSD).ObjectiveWe aimed to present the potential pathogenicity of CHD7 variants in pediatric patients with DSD.MethodsChoosing cases with CHD7 variants from DSD patients in Beijing Children's Hospital to assess for the study. Prediction software tools were used to predict variant pathogenicity in these subjects.ResultsAmong the 113 DSD patients, 22 cases had CHD7 variants. Twenty‐four different CHD7 variants were identified in the 22 DSD patients. Prediction software combined with ClinVar database information and their clinical manifestations revealed that, of the 18 patients with 46, XY DSD, two had CHARGE syndrome and two had Kallmann syndrome. Seven of the variants were highly categorized as “likely to be pathogenic” and seven as “suspected to be pathogenic”. Of the four patients with 46, XX DSD, three had ovotesticular DSD (c.305A>G, c.2788G>A, and c.3098G>A) and one had testicular DSD (c.2831G>A).InterpretationA high frequency of CHD7 variants was found in the DSD patients, especially those with 46, XY DSD. Thus, the detection of a pathogenic CHD7 variant could suggest a diagnosis of hypogonadotropic hypogonadism for 46, XY DSD patients, but pre‐pubescent patients should be reassessed in adolescence to confirm this diagnosis. This study also suggests that DNA sequencing could help to identify pre‐pubescent DSD patients. Further data are required to determine the connection between CHD7 variants and sex‐reversal in patients with 46, XX DSD, and the accumulation of these data is essential and necessary for DSD research.

Recent progress of NR5A1 gene mutation

NR5A1 gene mutation is one of the common cause of 46 XY dysplasia (46, XY disorder of sex development, 46, XY DSD), which is an autosomal dominant disease.It has wide phenotypes: 46, XY gonadal dysplasia is the most common one, site-specific mutations can lead to adrenal dysfunction and may affect the height.In recent years, more and more studies have shown that the mutation of NR5A1 gene can lead to 46, XX ovotesticular DSD and 46, XX testicular DSD.The disease is also characterized by hypergonadotropic hypogonadism, so LH and FSH are high, especially the FSH, leading to a decrease in LH/FSH.The treatment of NR5A1 gene mutation is mainly symptomatic.Gender identification needs to take many factors into consideration.Before puberty, children can use GnRHa to inhibit gonad development and avoid premature ovarian failure.In this review, recent progress of NR5A1 is summarized. Key words: NR5A1 mutant; Gonadoplasia; LH/FSH; Gonadal premature failure

29: Ovotesticular disorder of sexual development: a case report

To present a rare case of ovotesticular disorder of sexual development (OT-DSD). We present a 21-year-old patient with gynandromorphic genitalia and breast development diagnosed with 46,XX OT-DSD. He was raised as a male and desired correction of his feminized anatomic features. A computer tomography of the abdomen and pelvis demonstrated normal kidneys, bilateral ureters, a uterine horn, an intra-abdominal gonad on the left, a descended gonad on the right and a structure consistent with a vagina. On physical examination, the patient demonstrated the presence of bilateral, symmetrical breasts and the external genitalia showed the presence of a 7 cm long penile-like structure that was immobile and adherent to the ventral aspect of a clitoral hood. A small, presumed testis within the scrotum was noted only on the right side, while the testis and scrotum were absent on the left. A perineal opening appearing to be the vaginal introitus was ultimately identified as the urethra on further investigation. Intra-operative findings included a small, boggy uterine horn and a left gonad which appeared to be a normal ovary with a dilated left fallopian tube. Bilateral ureters with efflux were identified in the normal anatomical position leading to a normal appearing bladder. In accordance with the patient’s wishes, an abdominal hysterectomy, left salpingo-oophorectomy, right trans-scrotal testicular biopsies and bilateral simple mastectomy were performed. Histopathologic examination of the excised gonads was performed at our institution. Examination of the right trans-scrotal biopsy confirmed testicular tissue. Examination of the left-sided gonad was consistent with an ovarian tissue. Traditional cytogenetic analysis revealed 46, XX. Six months after the initial surgery, the patient underwent the second stage of gender confirmation surgery. Penile reconstructive surgery and metoidioplasty were performed by dividing the skin of the phallus/clitoris from the underlying cavernous body. The reconstruction of the penis was completed by advancing another skin flap from the left labia majora. The patient’s 6-month follow-up demonstrated an uncomplicated post-operative course, living as a male. For many children with ambiguous genitalia in the developing world, it is not until puberty before problems associated with feminization become apparent. Very often, as in our case, multiple surgical procedures are necessary to fulfill the gender choice of the patient. Most patients would prefer to live as a male because of cultural bias. However, it is rare that a patient in the developing world who has been feminized or masculinized during their post-pubescent years actually find surgeons to perform gender assignment surgery. This is usually due to the absence of knowledgeable medical resources and the prohibitive cost.View Large Image Figure ViewerDownload Hi-res image Download (PPT)View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Genetic evaluation of disorders of sex development: current practice and novel gene discovery.

As the pace of genetic discovery accelerates, genetic sequencing is increasingly applied to rare disease such as DSD (differences or disorders of sex development,) which has led to an increase in the number of novel variant-containing candidate genes identified. In this review, we will discuss several candidate genes which have recently been proposed as causative of DSD, as well as novel work in understanding gene regulation in the mouse gonad that may have implications for the DSD phenotype in humans. We performed a comprehensive search of PubMed through August 2018 to identify relevant peer-reviewed publications from 2017 to 2018 on DSD genetics. Seminal work has identified a critical gonadal enhancer of Sox9 in a mouse model. This enhancer is located in a region which had previously been implicated in both XX and XY DSD, though the specific enhancer and its role in Sox9 gene expression had not been defined. Novel candidate genes in XY gonadal dysgenesis (SOX8, ESR2) and XX ovotesticular DSD (NR2F2) have been described.

A Comparative Fiqh Study of the provisions of Hermaphrodite between Science and Personal Status

This research deals with the subject of Hermaphrodite and its provisions in the personal status, where in the first requirement of the concept of the Hermaphrodite between Islamic jurisprudence and Doctors, and found that there was a large consensus between the concept of the Hermaphrodite in the doctrine and its significance in medicine scientists, where they agreed that the collection between the reproductive tract of humankind. In the second requirement displays the search of the types of Hermaphrodite and the existence of an agreement between the Islamic Jurisprudence and the medicine scientists as a hermaphrodite two types: True hermaphroditism and Pseudo-hermaphroditism. A third requirement was to determine the gender of the Hermaphrodite where Islamic Jurisprudence adopted the external signs in determining sex, while the doctors relied on the clinical and laboratory testing, the external signs may be incompatible with the phenomenon as a result of the tests, so the reliance on virtual signs of Islamic Jurisprudence is not enough. The search then discussed issues related of personal status, where marriage is not allowed to Hermaphrodite until it becomes clear, also prevents the Khalwa. Hermaphrodite Legacy inherits the inheritance of the female and stops the rest of the heirs.

Vaginoplasty and creating labia minora in children with disorders of sex development.

To report current results of vaginoplasty using the mucosa of the prepuce, and creating labia minora by penile skin in children with disorders of sex development (DSD). In 10years, we have performed 22 vaginoplasties using the described technique of vaginoplasty, 21 patients with 46, XX DSD and 1 ovotesticular DSD. The assessment of the results of this technique of vaginoplasty was undertaken in several stages: (a) The evaluation of the cosmetic result. (b) The research for a urinary incontinence and urethrovaginal fistulas. (c) The research for a vaginal stenosis by the introduction of a lubricated feeding tube into the vaginal cavity. The labia minora was evaluated by three criteria: its skin should be thin and very supple, it should have a free edge which partially or totally covers the clitoris, urethral meatus, and vaginal orifice; and it is preferable that its color be darker than the rest of the skin. The cosmetic outcome was considered by parents and the surgeon as very satisfactory in 11 patients (50% of cases), satisfactory in 4 patients (18.2%), and unsatisfactory in 7 patients (31.8%). The postoperative complications were five cases of proximal stenosis (22.7%), one distal stenosis (stenosis of introitus) and two necrosis of the preputial flap. No urethrovaginal fistula and urinary incontinence were reported. In infant and young child, when it is difficult to make use of complete urogenital mobilization, the mucosa of the prepuce can be an alternative to create a neovagina, its histological constitution is identical to a vaginal wall, and it does not prevent to have a good labia minora.

Elevated incidence of freemartinism in pigs detected by droplet digital PCR and cytogenetic techniques

Freemartinism is a disorder of sex development (DSD) caused by the formation of placental anastomoses between fetuses of different sex. It leads to development of an abnormal reproductive tract in the female fetus, including the presence of testes or ovotestes. In pig production, such conditions can affect both reproductive performance and meat quality, through undesired boar taint. A common approach to diagnosing freemartinism is to detect leukocyte chimerism (XX/XY). In the study described here, we performed a complex evaluation of 28 DSD pigs with ambiguous external genitalia (enlarged clitoris, presence of scrotum, etc.). Sex chromosomes were cytogenetically identified by Giemsa staining, as well as with fluorescence in situ hybridization (FISH), while Y-linked (ZFY) and X-linked (ZFX) genes were detected by PCR-RFLP. Histological analysis of the gonads was performed on eosin–hematoxylin-stained microscope slides. Chromosome studies revealed that, of 28 DSD animals, 20 were freemartins (38,XX/38,XY), 2 had a female karyotype (38,XX), and 6 had a male karyotype (38,XY). Analysis of breeding data showed that the mean litter size in which DSD animals occurred was about 17. Histology of the gonads could be performed for 8 DSD pigs, including 6 freemartins and 2 XX DSD. In all these cases, testicular tissue without signs of spermatogenesis was seen. In XX DSD pigs, a copy number variation (CNV) polymorphism downstream from SOX9, tentatively associated with this type of DSD, was detected by FISH. On the other hand, the background of the XY DSD remains unknown. Since cytogenetic analysis is labor-intensive and time-consuming, we evaluated the usefulness of the droplet digital PCR (ddPCR) approach to diagnosing XX/XY leukocyte chimerism. Estimation of X and Y chromosome copy numbers was based on the quantitative detection of AMELX and AMELY genes. Different sex chromosome sets (XX, XY and XX/XY) were unequivocally identified by ddPCR. In conclusion, we suggest that freemartinism, beside testicular or ovotesticular XX DSD, is an emerging problem in highly prolific pigs and that detection of XX/XY leukocyte chimerism can be performed using a fast and reliable ddPCR approach.

True hermaphroditism with seminoma: A case report.

The aim of the present study was to discuss the diagnosis and treatment of a patient with true hermaphroditism complicated by seminoma. The patient was a 35-year-old man who was admitted to the Peking University Shenzhen Hospital with a retractable mass in the left inguinal region for 20 years. A computed tomography examination revealed right cryptorchidism. The postoperative pathology suggested true hermaphroditism with a seminoma. The results of immunohistochemical examination were as follows: Sal-like protein 4+ (partially weak); octamer-binding transcription factor 4+ (partially weak); CD117+; cytokeratin+; CD30-, α-fetoprotein-, inhibin-α-. The karyotype was 46, XY. Adult true hermaphroditism combined with seminoma is rare in clinical practice. Combined histopathological analysis, immunophenotype detection and karyotype analysis are of great value in the diagnosis and differential diagnosis. Early intervention and combined surgery with radiotherapy and chemotherapy can significantly improve the prognosis of such patients.

A Novel Homozygous Missense Mutation in the FU-CRD2 Domain of the R-spondin1 Gene Associated with Familial 46,XX DSD

R-spondin proteins are secreted agonists of canonical WNT/β-catenin signaling. Homozygous RSPO1 mutations cause a syndrome of 46,XX disorder of sexual development (DSD), palmoplantar keratoderma (PPK), and predisposition to squamous cell carcinoma. We report exome sequencing data of two 46,XX siblings, one with testicular DSD and the other with suspected ovotesticular DSD. Both have PPK and hearing impairment and carried a novel homozygous mutation c.332G>A (p.Cys111Tyr) located in the highly conserved furin-like cysteine-rich domain-2 (FU-CRD2). Cysteines in the FU-CRDs are strictly conserved, indicating their functional importance in WNT signaling through interaction with the leucine-rich repeat-containing G-protein-coupled receptors. This is the first RSPO1 missense mutation reported in association with human disease.

Pygomelia and True Hermaphroditism in a Nine Week Old Large White Piglet Case Report

Abstract A nine weeks old female Large White piglet which was presented to the Veterinary Teaching Hospital, Federal University of Agriculture, Abeokuta, with a complaint of extra limbs was diagnosed with pygomelia and concurrent true hermaphroditism based on gross morphologic features, radiography, exploratory laparotomy and histopathology of the malformed organs. The piglet had two well-developed extra hind limbs consisting of the femur, tibia, fibula and the phalanges. Radiographically, the accessory limbs were attached to the ischium through a rudimentary pelvic bone. The supernumerary limbs were smaller than the normal appendages, but contained equal digits. The anal orifice was observed cranial to the right supernumerary limb. Caudal to the left supernumerary limb a rudimentary penis was observed. Two oval shaped fibrous masses were palpated in the inguinal canal of the piglet. In addition, there was a transparent tubular tract measuring 24 cm in length which contained serous fluid. The right kidney was rudimentary measuring 2.10 cm, while the left kidney appeared hypertrophied measuring 6.10 cm. The histology of the left kidney showed dysplastic areas of undifferentiated mesenchymal stroma in the cortex and medulla with the presence of groups of immature glomeruli in the cortex. The tubules in the medulla were scanty in number and had atypical epithelium. The adrenal glands had normal architecture with ectopic adrenal tissue in the adrenal capsule, while the ovaries and uterus were normal. It was concluded that the complex anomalies in the piglet might be as a result of a complex mode of inheritance.

Analysis of Presentations and Outcomes of Care of Children with Disorders of Sexual Development in a Nigerian Hospital.

To describe the presentation, diagnosis, management, and short-term outcome of children with disorders of sexual development (DSD) in the context of multidisciplinary team care. Prospective descriptive study. University Teaching Hospital. All children who presented with genital ambiguity. Records of all patients diagnosed and managed for DSD between January 2011 and December 2016 were reviewed. The care pathway included clinical, laboratory, internal genitalia evaluation, and panel (including parents) meeting. Fifteen children presented with DSD at a median age of 20months. Only 5/15 (33.3%) presented in the neonatal period. Ten of fifteen patients (66.7%) presented with genital ambiguity. Ovotesticular DSD was the most common diagnosis (9/15; 60%). Seven of the patients were genetically female (46, XX), 1 was genetically male (46, XY) and 1 without genetic diagnosis. Six patients were assigned male gender and they underwent male genitoplasty. Five of them had excision of Müllerian structures with gonadectomy. Three of fifteen patients (20%) were diagnosed as 46, XX DSD, at a median age of 7years. All of them were due to congenital adrenal hyperplasia and underwent female genitoplasty. Two patients were diagnosed as XY, DSD. They were both raised as female at presentation and were reassigned male sex. Both had urethroplasty done. Four patients had postoperative urethrocutaneous fistula and 1 had partial wound dehiscence. The median follow-up period was 21months (interquartile range, 2-26months). The frequency of ovotesticular DSD is high in our setting. The decision of sex assignment was finally made at a median age of 7.5months in most of our patients with satisfactory short-term surgical outcome.

The restrained inguinal hernia at children with violation a floor form

The most common surgical pathology of childhood, which is necessary for doctors of all specialties, is the inguinal hernia. In the treatment of this pathology, both open procedure and laparoscopic surgery are used. Infringement of a hernia, manifested by sudden or gradual compression of its contents in the gates, is a dangerous complication.Violation of the formation of sex - a condition associated with the clinical and biochemical manifestation of the discrepancy between the genetic, gonadal and phenotypic sex of the child. Traditionally, the term “hermaphroditism” is used to describe this state. A distinction is recognized between true hermaphroditism (gonadal) and false hermaphroditism (the presence of signs opposite to the gonadal sex of the subject). True hermaphroditism is a rare disease. False female hermaphroditism is attributed to conditions in which the female karyotype and gonads that are characteristic of the female sex are determined. But the external genitalia have a bisexual structure. The most common cause of false female hermaphroditism is congenital dysfunction of the adrenal cortex.According to several authors, a frequent cause of amblysexuality of the genitals in newborns is mixed gonadal dysgenesis – a condition in which phenotypic men or women have an egg on one side, and a gonadal cord located either in a wide bundle or on the pelvic wall and consisting from the stroma of the ovary on the other. At birth, the external genitalia are usually the penis, the uro-genital sinus and the labia genitalia, which are intertwined in the scrotum.Evaluation of the patient’s local status with violation of the formation of sex in the occurrence of surgical pathology is not an easy task, since the appearance of the external genitalia in the XX and XY subjects is the same. In 2015, in connection with the injured inguinal hernia in the department of pediatric surgery No. 1, the State Children’s Clinical Hospital “OKB No. 2” in Tyumen received treatment for two children with a violation of the formation of sex. Difficulties in interpreting intraoperative data prompted us to describe these cases.

P53: True hermaphroditism in a 46, XX girl who had normal secondary sex characteristic and normal external genitalia

P53: True hermaphroditism in a 46, XX girl who had normal secondary sex characteristic and normal external genitalia

Management of pediatric patients with DSD and ambiguous genitalia: Balancing the child's moral claims to self-determination with parental values and preferences

A central ethical dilemma in management of the patient with a disorder of sex development (DSD) is the potential conflict between respect for the fundamental right of the child for physical and emotional integrity and self-determination, and the right of parents to serve as surrogate decision-makers and act in their child's best interest. Over the past 2 years we have encountered three complex DSD cases on the spectrum of mixed gonadal dysgenesis to ovotesticular DSD in which gender assignment and therefore optimal surgical management was uncertain. All patients had mosaic karyotypes with Y chromosome, dysgenetic ovary and dysgenetic testis, a urogenital sinus, and prominent phallus. In all three cases a team approach was taken to assess functional potential and risks along either gender pathway and to develop a spectrum of treatment options for parental consideration, including: 1. masculinization with removal of dysgenetic ovary; 2. initial vaginoplasty but with retention of the phallus (±bilateral gonadectomy); 3. initial vaginoplasty with "burial" of corporal bodies (Pippi Salle procedure) (±bilateral gonadectomy); 4. full feminization: vaginoplasty and clitoroplasty (with bilateral gonadectomy); 5. no surgical intervention. In all three cases, after consideration of risks and benefits of all options, parents selected option 2: gonadectomy to eliminate tumor risk and vaginoplasty, taking advantage of the child's young age to exteriorize urinary and reproductive tracts to avoid incontinence and infection and supporting parental bias toward female gender, but preservation of phallic structures to ensure a male option should the patient later declare a male gender identity. Parents of the three patients were contacted post-operatively (at 7, 17, and 22 months) for follow-up. All (3/3) regarded their child's development and wellbeing positively, and their own decisions regarding gender assignment and surgical plan favorably. All (3/3) regarded the team advisory process as balanced and supportive. In the setting of exposure of the neonatal brain to testosterone, vaginoplasty and phallic preservation afforded a balance between parental preferences and preservation of anatomic options, allowing potential reconstruction of male or female phenotype as gender identity is ascertained thereby respecting both parent and patient rights. Parents valued a spectrum of options, transparency, and the team decision-making process.

Haploinsufficiency of the DMRT Gene Cluster in a Case with 46,XY Ovotesticular Disorder of Sexual Development

Background:Ovotesticular disorder is characterized by the presence of testicular and ovarian tissues in the same individual. Single gene mutations in SRY, SOX9, DMRT1 and DAX1 can lead to ovotesticular disorder of sexual development.Case Report:Herein, we report a 3-month-old phenotypically female baby in whom differentiated tissues of both Müllerian and Wolffian ducts were detected on pathological analysis of laparoscopic biopsy material. Chromosomal analysis observed 46,XY, der(9)t(3;9)(p25;p24) with deletion of 9p24.3p23 including the DMRT gene cluster and duplication of 3p26.3p24.3 on array comparative genomic hybridisation.Conclusion:In support of previous literature, we found that haploinsufficiency of the DMRT gene cluster leads to ovotesticular disorder of sexual development. In addition, we emphasize that array comparative genomic hybridisation is an important technique in the molecular diagnosis of ovotesticular disorder of sexual.

Gonadal Steroid Hormones Levels in a Bitch with True Bilateral Hermaphroditism

Gonadal Steroid Hormones Levels in a Bitch with True Bilateral Hermaphroditism