True Hermaphroditism Research Articles

Unusual Case of Ovotesticular DSD Presented at Adulthood with Mosaic Karyotype, Full Functioning Mullerian Structure, Two Ovaries, and One Ovotestis

Disorder of Sex Development (DSD) is a condition where there is a misalignment of gonads or chromosomes with the genitalia. One of the rarest forms of DSD is Ovotesticular DSD (OT-DSD) which is also known as True Hermaphroditism. It is characterized by the presence of both ovarian and testicular tissues in the same individual. This condition usually presents with ambiguous genitalia either at birth or later in life. OT-DSD is a rare form of DSD, with an estimated incidence of less than one in every 20,000 individuals, which represents less than 5% of all DSD cases. However, it appears to be more common in African countries such as Kenya or South Africa. OT-DSD often displays a diverse range of phenotypes with varying penetrance. In this report, we describe a rare case of OT-DSD where the individual was raised as a female and presented with ambiguous genitalia, a fully functioning Mullerian structure in adulthood, and 3 gonads. We provide clinical and genetic details of the case and review relevant literature on the subject.

7709 Ovotesticular Difference of Sex Development: Prognostic Evaluation, Sex Assignment, and Ethics

Abstract Disclosure: X. Xu: None. Y. Lin: None. B. Shivanna: None. A. Lee: None. J.C. Hakim: None. D.G. Mann: None. L.M. Noll: None. P. Georgiadis: None. S.K. Gunn: None. L.P. Karaviti: None. Background: Our case provides the identification and management of a newborn baby with ovotesticular syndrome, which was formerly known as true hermaphroditism. The term was classically derived from Greek mythology in which the deity 'Hermaphroditus', merging with the nymph Salamis, embodied both male and female attributes. The term 'true hermaphroditism' is now avoided due to its stigmatizing connotations. Ovotesticular difference of sex development (DSD) is an exceedingly rare condition, occurring in fewer than 1 in 20,000 births. This condition involves the coexistence of functional ovarian and testicular tissue within one individual, presenting a challenge in sex assignment due to unpredictable gender development. Clinical Case: This is a single case of the presence of ovarian and testicular differentiation on one side and a transitional zone of mixed pattern. Prenatal genetic testing consistent 46,XX karyotype. Initial ultrasound at the outside hospital revealed a uterus and right testicle. The baby exhibited Prader stage 4 genitalia, with a palpable gonad in the right labioscrotal area and the left gonad not palpable. Prophylactic hydrocortisone was started due to concerns regarding NR5A1/SF1 mutation. Further evaluations, including genetic tests, hormonal assessments, urinalysis and kidney ultrasound for the WT1 mutation, and scrotal and pelvic ultrasounds, were conducted. The high-dose ACTH stimulation test ruled out adrenal insufficiency. The testosterone level was in the male range, and the HCG stimulation test further confirmed functioning Leydig cells. The postnatal karyotype was 46,XX, and chromosome microarray analysis showed no abnormalities. Our approach to this case was multidisciplinary, including our endocrine experts, urologist, gynecologist, ethicist, and psychologist. We discussed the fluidity of sex assignment and addressed the degree of virilization, nature of the gonadal tissue, and emphasized the necessity of regular clinical follow-up. Our main concern was to educate the parents and protect the choices of the child. In this case, the child assumed a male sex assignment, as a result of the decision-making process between our team and the parents. In this context we did emphasize the fluidity of sex assignment. Clinical Lesson: Long-term outcomes for ovotesticular DSD remain understudied. Existing reports highlight varying rates of gender dysphoria, sexual function, and psychological well-being. Our approach to managing ovotesticular DSD involved a framework emphasizing ethical considerations and parental involvement. We advocated for and practiced a shared decision-making model involving healthcare providers, parents, and ultimately the patient. Presentation: 6/3/2024

Laparoscopy versus ultrasonography for the evaluation of Müllerian duct remnants in male patients with disorder of sex differentiation

BackgroundThe diagnosis of male differences of sex development is a challenging multidisciplinary team task, that requires external genital evaluation, karyotyping, hormonal profiling, radiological work up and frequently diagnostic laparoscopy and biopsy, for evaluation of internal duct system and nature of gonads. The debate still persists regarding the best diagnostic modality for accurate visualization of Müllerian duct remnants (MDRs) in those patients.The aim of the study was to compare between laparoscopy (L) and ultrasonography (US) regarding the diagnostic accuracy in detection of Müllerian duct remnants, in addition to describing their anatomical nature and relations with the male duct system, in patients with male DSD, with various karyotypes.MethodsWe prospectively included 20 patients with male DSD, mostly due to 46 XY DSD or chromosomal DSD, over 2 years. The medical and radiological data were collected and analyzed.ResultsThe age at the first diagnostic intervention ranged from 8 to 24 months (mean: 17 months). There were 14 patients with 46XY DSD with variable diagnoses (3 ovotesticular DSD, 3 partial gonadal dysgenesis, 6 persistent Müllerian duct remnants syndrome and 2 mixed gonadal dysgenesis). Two patients with 46XX DSD were included (one XX male, and one patient with ovotesticular DSD). One patient with chimerism (46XY/46XX) and three patients with 46XY/45XO mixed gonadal dysgenesis were also recruited. MDRs were evident in all cases (100%) by laparoscopy, only 25% (n = 5) were visualized by US. There was a statistically significant difference between laparoscopy and US regarding gonadal and MDR visualization, being higher with laparoscopy (p values, 0.0180 and 0.001).ConclusionsUltrasonography failed to visualize Müllerian remnants in 75% of patients with complex DSD. On the other hand, laparoscopy provided optimum visualization of MDRs and gonads in those children.

Intersex Pretenders.

False claims of having an intersex condition have been observed in print, video, Internet media, and in live presentations. Claims of being intersexed in publicly accessible media were examined and evidence that they were false was considered sufficiently conclusive in 37 cases. Falsity was most often detected due to medical implausibility and/or inconsistency, but sometimes also using information from third-party or published sources. The majority, 26/37, of cases were natal males; 11/37 were natal females. Almost all (34/37) were transgendered, living, or aspiring to live, in their non-natal sex or as socially intergender. The most commonly claimed diagnosis was ovotesticular disorder ("true hermaphroditism") due to chimerism, an actually uncommon cause of authentic intersexuality. Motivations for pretending to be intersexed were inferred from statements and behaviors and were varied. Some such pretenders appear to be avoiding the external or internalized stigma of an actual transgendered condition. Some appear, similarly to persons with factitious disorder, to be seeking attention and/or the role of a sick, disadvantaged, or victimized person. Some showed evidence of paraphilia, most frequently autogynephilia, and, in several cases, paraphilic diaperism. For some cases, such claims had been accepted as authentic by journalists or social scientists and repeated as true in published material.

68. Inguinal Hernia Containing the Uterus in a Case of 46 XX Ovotesticular Disorder of Sex Development

68. Inguinal Hernia Containing the Uterus in a Case of 46 XX Ovotesticular Disorder of Sex Development

Suspected True Hermaphroditism in a Free-ranging Gray Wolf (Canis lupus) in Interior Alaska, USA.

Hermaphroditism or intersexuality occurs endogenously in most mammal species. We document the behavior and physical and anatomic appearance of a suspected true hermaphroditic free-ranging wild gray wolf (Canis lupus) in Denali National Park and Preserve, Alaska, USA.

Clinicopathological analysis of gonadal differentiation of sex development disorder

Objective: To investigate pathological features and differential diagnosis in the gonads with disorder of sex development. Methods: Thirty-six cases of clinically diagnosed hermaphroditism with gonadal biopsy in the Department of Pathology, the Seventh Medical Center of People's Liberation Army General Hospital from April 2007 to July 2021, were collected. All biopsy pathological sections were reviewed, and the gonadal cases with abnormal pathological morphology were screened out. The clinical and imaging data and karyotype of these cases were reviewed. Additional immunohistochemical staining was performed and relevant literature was reviewed. Results: Seven cases of ovotesticular disorder of sex development (OTDSD) were identified, which were characterized by the presence of testicular and ovarian differentiation in the same individual. All patients were under 15 years old and presented with abnormal appearance of external genitalia, and the ratio of male to female was 2∶5. Ultrasonography showed testicular structure in all female patients and cryptorchidism in all male patients. The most common karyotype was 46, XX. One case with undifferentiated gonadal tissue (UGT) and one case with streak gonads were screened out. UGT germ cells were neither in seminiferous tubules nor in follicles, but randomly distributed in an ovarial-type interstitial background, sometimes accompanied by immature sex cords. Streak gonads resembled UGT without germ cells. FOXL2 was positive in granulosa cells, but negative in Sertoli cells. SOX9 expression was opposite. OCT4 was weakly positively/negatively expressed in oocytes and positively expressed in the germ nuclei of UGT. Conclusions: Four differentiation patterns need to be identified in the gonadal biopsy: ovarian differentiation, testicular differentiation, undifferentiated gonadal tissue and streak gonad. The positive expression of SOX9 indicates testicular differentiation, while the positive expression of FOXL2 confirms ovarian differentiation, and the expression of both markers in the same tissue indicates ovotestis differentiation. It is very important to identify UGT, because that has a high probability of developing into gonadoblastoma in the future.

Laparoscopic Hysterectomy with Bilateral Gonadectomy in True Hermaphroditism: A Case Report

Laparoscopic Hysterectomy with Bilateral Gonadectomy in True Hermaphroditism: A Case Report

Late Diagnosis of Ovotesticular Disorders of Sexual Development: A Case Report and Literature Review

Late Diagnosis of Ovotesticular Disorders of Sexual Development: A Case Report and Literature Review

''Should the child be raised as male or female?'' The evaluation and management of different causes of ambiguous genital appearance in children

Diagnosing, managing and assigning gender for different causes of ambiguous genitalia in children can be challenging. This article will discuss about the types, diagnosis and treatment of disorders of sex development including congenital adrenal hyperplasia, 46 XY mixed gonadal dysgenesis and 46XY ovotesticular disorder of sex development. This article reports about 3 cases of disorders of sex development. The first case is about a three-year-old girl who was diagnosed with congenital adrenal hyperplasia, genital examination revealed clitoromegaly and a single urogenital sinus; she was managed medically and surgically. The second case is about a one-month-old child with 46XY karyotype, genital examination revealed penoscrotal hypospadias with right palpable and left impalpable gonads. Patient underwent diagnostic laparoscopy in which both female and male internal organs were found; based on these results a diagnosis of 46XY ovotesticular disorder of sex development was made. The third case is about a 3-month-old child with 46XY karyotype, genital examination revealed hypospadias with bilateral impalpable gonads. Diagnostic laparoscopy showed a uterus with a bilateral ovary-looking gonad; histopathology of the bilateral ovary-looking gonads was consistent with testicular tissue. Based on the above, a diagnosis of 46XY mixed gonadal dysgenesis was made. Disorders of sex development are classified into three main categories based on the karyotype, XX, XY and sex chromosome other than XX and XY. Laboratory investigations, karyotype, genetic analysis, imaging, surgery and tissue biopsy, all aid in diagnosing, deciding gender identity and managing different types of disorders of sex development.

Ovotesticular disorder of sex development in a 46 XY adolescent: a rare case report with review of the literature

Introduction: Ovotestis is a rare cause of sexual ambiguity characterized by the presence in a patient of both testicular and ovarian tissue, leading to the development of both male and female structures. We report a case of ovotestis diagnosed in an adolescent, with a review of the literature.Case ReportA 15-year-old patient presented with a right scrotal swelling associated with gynecomastia. Histology showed a juxtaposition of ovarian stroma with ovarian follicle and seminiferous tubules. Karyotype revealed a male subject (XY). We have therefore retained the diagnosis of ovotesticular disorders of sex development.ConclusionOvotestis is a rare finding, heterogeneous in its genetic etiology and clinical presentation. While many patients are diagnosed during infancy or childhood, we presented a case diagnosed in a 15-year-old adolescent.

Primary Amenorrhea Due to Ovotesticular Disorder of Sexual Development

Primary amenorrhea with ambiguous genitalia is a diagnostic challenge to physicians. Ovotesticular disorder of sexual development is a one cause for that which need gonadectomy followed by histological assessment to confirm the diagnosis. This is a case of ovotesticular disorder of sexual development which presented with primary amenorrhea with ambiguous genitalia.

SAT395 Gender Dysphoria In A Patient With Ovotesticular Disorder Of Sex Development

Abstract Disclosure: T. Moreno: None. P. Rodrigues: None. S. Ribeiro: None. D.M. Carvalho: None. Introduction: Ovotesticular disorder of sex development (OT-DSD) is a rare condition characterized by the presence of both ovarian and testicular tissue in the gonads. Management and sex designation of these patients depend on several factors and an underlying potential for gender dysphoria should be acknowledged.Clinical Case: A 12-month-old patient from Guinea-Bissau, born from consanguineous parents, was referred to Pediatric Surgery due to atypical genitalia. Karyotype was 46,XX and SRY gene analysis was negative. Genitoscopy showed absence of a vagina and a uterus was not found on magnetic resonance imaging. An exploratory laparotomy and biopsy of the gonads was performed. The pathology report confirmed the presence of gonadal ovarian and testicular tissue, establishing the diagnosis of OT-DSD. Surgical removal of both gonads and clitoroplasty was performed and a female sex designation was attributed. Endocrinology follow-up was started at the age of 8 and the first physical examination revealed weight 48.6 kg (> P97), height 135.5 cm (P90–97); Tanner stage I (P1A1M0) and a blind vagina with normal clitoris size. Blood tests showed FSH 12.53 mUI/L, LH 1.07 mUI/L, estradiol 5.8 pg/mL and total testosterone 0.04 ng/mL. Reconstructive surgery for a neovagina was performed at 13-years-old and, two years later, the patient was started on hormone replacement therapy with transdermic estradiol. At the age of 16, the patient manifested gender dysphoria issues, decided to stop estradiol and was referred for psychiatric evaluation. Two years later, intramuscular testosterone enanthate was initiated but treatment was stopped after a six-month trial, as the patient claims to identify as male but is not interested in seeking hormone treatment at this point.Conclusion: OT-DSD is an uncommon condition, raising issues of gender assignment that are dependent on factors such as age at diagnosis, phenotype, internal structures and reproductive potential. Scarce data exists on long-term outcomes in OT-DSD, including the frequency of gender dysphoria in these patients. Gender identity is an important factor to consider on long-term follow-up of OT-DSD patients. Presentation: Saturday, June 17, 2023

THU184 Varying Presentations Of 46XX OTD

Abstract Disclosure: I. Mishra: None. S.K. Sahoo: None. A.K. Baliarsinha: None. Ovotesticular disorder of sex development (OT-DSD) is a condition associated with presence of both testicular and ovarian tissue in same individual, in which these tissues may co-exist either in the same gonad or independently. 46 XXOTD are most common. We describe 3 cases of 46 XXOTD presenting in their post pubertal years with varied presentation. Case 1: 19 year old reared as male presented with peripubertal gynaecomastia and cyclical pain abdomen. On examination there was symmetrical genitalia, non palpable gonads, microphallus, single genital opening below phallus (Prader 3), pubic hair stage 4, axillary hair stage 3 and breast stage 5. Biochemical evaluation revealed serum testosterone (19 ng/dl), 17-hydroxy progesterone (1.7ng/ml), LH (2.6IU/L), FSH (8.6IU/L) and E2(112pg/ml). Karyotype 46XX, FISH SRY negative. USG abdomen s/o uterus like structure with absent wollfian remnants. Post laproscopy histopathology s/o bilateral ovotestis, normal ovarian stroma with hyalinized seminiferous tubule, sertoli cells and leydig cells. Case 2: 18 year old reared as male presented with peripubertal gynaecomastia and genital ambiguity. On examination there was asymmetrical genitalia, palpable right scrotal gonads, phallus, single genital opening at base of phallus, pubic hair stage 4, axillary hair stage 3 and breast stage 5. Biochemical evaluation revealed serum testosterone (110ng/dl), LH (4.6IU/L), FSH (11.2IU/L) and E2(46pg/ml). Karyotype 46XX.USG abdomen s/o hypoplastic uterus like structure with possible ovary in left side of pelvis, hypoplastic testis in right scrotal sac. Post laproscopy histopathology was s/o left dysgenetic ovary, and hypoplastic uterus. Case 3: 17 year old reared as male presented with peripubertal gynaecomastia. On examination there was symmetrical genitalia, non palpable gonads, microphallus, single genital opening at the base of phallus (Prader 4), pubic hair stage 4, axillary hair stage 2 and breast stage 4. Biochemical evaluation revealed serum testosterone (98ng/dl), 17-hydroxyprogesterone (0.58ng/ml), LH (4.05IU/L), FSH (7.12IU/L) and E2 (96 pg/ml). Karyotype 46XX, FISH SRY positive. USG abdomen s/o uterus like structure with apparent left ovary and non visualization of right gonads. Post laproscopy histopathology s/o rudimentary uterus, left ovary with follicles and right gonads showing semineferous tubules with sertoli cells and few hyperplastic leydig cells. 46 XX OTDSD presents with wide phenotypic variability, which influences decisions about gender assignment and need of surgery. Conservative therapy, whenever feasible, is desirable to achieve fertility. Multidisciplinary team approach is required for healthy physical and psychological well-beings of these individuals. Presentation: Thursday, June 15, 2023

Dermatologic care of patients with differences of sex development.

Differences of sex development (DSD or disorders of sex development) are uncommon congenital conditions, characterized by atypical development of chromosomal, gonadal, or anatomic sex. Dermatologic care is an important component of the multidisciplinary care needed for individuals with DSD. This article discusses the most common primary dermatologic manifestations of DSD in addition to the cutaneous manifestations of hormonal and surgical therapies in individuals with DSD. Published articles including case series and case reports on PubMed. Selection was conducted by examining existing literature with a team of multidisciplinary specialists. Narrative review. This article was not conducted as a systematic review. In Klinefelter syndrome, refractory leg ulcers and incontinentia pigmenti have been described. Turner syndrome is associated with lymphatic malformations, halo nevi, dermatitis, and psoriasis. Virilization can be seen in some forms of congenital adrenal hyperplasia, where acne and hirsutism are common. Dermatologists should consider teratogenic risk for treatments of skin conditions in DSD depending on pregnancy potential. Testosterone replacement, commonly used for Klinefelter syndrome, androgen insensitivity syndrome, 5-alpha reductase deficiency, gonadal dysgenesis, or ovotesticular DSD, may cause acne.

High-Throughput Splicing Assays Identify Known and Novel WT1 Exon 9 Variants in Nephrotic Syndrome

Frasier syndrome (FS) is a rare Mendelian form of nephrotic syndrome (NS) caused by variants which disrupt the proper splicing of WT1. This key transcription factor gene is alternatively spliced at exon 9 to produce 2 isoforms ("KTS+" and "KTS-"), which are normally expressed in the kidney at a ∼2:1 (KTS+:KTS-) ratio. FS results from variants that reduce this ratio by disrupting the splice donor of the KTS+ isoform. FS is extremely rare, and it is unclear whether any variants beyond the 8 already known could cause FS. To prospectively identify other splicing-disruptive variants, we leveraged a massively parallel splicing assay. We tested every possible single nucleotide variant (n= 519) in and around WT1 exon 9 for effects upon exon inclusion and KTS+/- ratio. Splice disruptive variants (SDVs) made up 11% of the tested point variants overall and were tightly concentrated near the canonical acceptor and the KTS+/- alternate donors. Our map successfully identified all 8 known FS or focal segmental glomerulosclerosis (FSGS) variants and 16 additional novel variants which were comparably disruptive to these known pathogenic variants. We also identified 19 variants that, conversely, increased the KTS+/KTS- ratio, of which 2 are observed in unrelated individuals with 46,XX ovotesticular disorder of sex development (46,XX OTDSD). This splicing effect map can serve as functional evidence to guide the clinical interpretation of newly observed variants in and around WT1 exon9.

An Unusual Clinical and Radiological Presentation of Ovotesticular Disorders of Sex Development with Male and Female External Genitalia: A Case Report

Background: Ovotesticular disorders of sex development (ODSD), previously known as true hermaphroditism, is a rare disorder of sexual differentiation that causes ambiguity in external genitalia and the presence of both ovarian and testicular elements in the gonads. The condition is characterised by the existence of testicular tissue with distinctive tubules and ovarian tissue in the same gonad (ovotestis), or separately in an individual. The most common cytogenetic karyotype is 46,XX. The age and presentation of symptoms vary, but typically include hypospadias, urogenital sinus, inguinal hernia, cryptorchidism, and gynaecomastia during the peripubertal age, as well as lower abdominal mass. Case Presentation: A 15-year-old female exhibited typical male genitalia, including a normal penile shaft, scrotal sac, palpable testes, and a urethral opening, with a separate vaginal opening located between the penile shaft and scrotum. Pelvic MRI confirmed the presence of both testes within the scrotal sac and an infantile-sized uterus with a central endometrium, as well as a left-sided ovary in the pelvic region. The right ovary was not seen. Correlative ultrasound confirmed these findings and indicated that the testes had a normal echo texture and vascularity. The patient was diagnosed with ODSD, and further hormonal testing was recommended. Conclusions: ODSD is a rare cause of genital ambiguity. Typically, both paramesonephric and mesonephric duct derivatives are seen, and most of the affected individuals present as neonates or infants with ambiguous external genitalia. At peripubertal age, the symptoms typically include hypospadias, urogenital sinus, inguinal hernia, unilateral or bilateral cryptorchidism, and gynaecomastia. Fertility is not uncommon and has been reported in female-reared patients. The ovotestis is the commonest gonad in people with ODSD and are known to be predisposed to germ cell tumours. Over 500 cases of ODSD have been reported in the literature. Ultrasound is the first line of investigation used to see the pelvic organs. The non-invasive test of choice for detecting paramesonephric and mesonephric duct derivatives is an MRI pelvis. The purpose of this paper is to describe various clinical and radiological features associated with ODSD.

Ovotesticular Disorder of Sex Development in a Tertiary Care Center in North India: A Single-center Analysis over a 5-year Period

Abstract Background: Disorders of sexual development (DSD) encompass a group of congenital conditions characterized by diverse genotypic and phenotypic variations. Ovotesticular (OT) DSD is a distinctive subtype within this spectrum. Among the array of DSD, OT-DSD stands as one of the most infrequent anomalies, with reported prevalence rates as scarce as 1 in 83,000. This study aims to elucidate the clinical, hormonal, cytogenetic, surgical, and histopathological characteristics of OT disorder of sex development (OT-DSD) within a tertiary center in North India. Methodology: A retrospective analysis was conducted, involving a comprehensive review of records pertaining to OT-DSD patients from the years 2018 to 2022, all of whom were incorporated into the study. Results: The mean age of presentation in this study was 10 years, spanning from 6 to 15 years. Predominantly, the affected individuals were male, with a solitary patient representing the female category. Clinical manifestations displayed a spectrum encompassing genital ambiguity, inguinal swelling, and primary amenorrhea. The karyotypes observed were 46,XX in four patients and 46,XY in one patient. A holistic assessment, inclusive of clinical evaluation, hormonal assays, pelvic ultrasonography, and surgical intervention when necessary, was administered to all patients. Among these cases, three patients were reared as males, their gender assignment driven by external genital appearance and sociocultural influences. Notably, none of the patients manifested gonadal tumors during the course of the study. Conclusion: In cases of ambiguous genitalia, the consideration of OT-DSD should be integral to the differential diagnosis, underscoring the significance of heightened clinical awareness and informed decision-making.

A Young Boy with Gynecomastia

Ovotesticular disorder of sex development (ovotesticular DSD) is defined as the presence of testicular and ovarian tissue in the same individual. Both external and internal genitalia of patients with ovotesticular DSD display a spectrum of phenotypes. Most children present with ambiguous genitalia in combination with unilateral or bilateral undescended gonads. We present late-diagnosed boy who presented with bilateral enlargement of the breast (gynecomastia) and male external genitalia. One should consider the possibility of ovotesticular DSD when managing boys with gynecomastia.

True hermaphroditism: A nightmare for an adult

Abstract The disorder of sex development is a rare disorder that usually occurs in early childhood. As adults, those with disorder of sexual development present with gynecomastia, primary amenorrhea, and primary infertility, which often causes great psychological impact. We report a unique case of a male adult hermaphrodite presenting with hematometra and hematosalpinx. Early management including psychiatry counseling, gender reassignment, and surgery is essential. Our patient underwent müllerian tissue removal with phallus reconstruction.