Disorders Of Sex Development Research Articles

The prevailing social stigma around disorders of sexual development in developing countries

Disorders of sexual development (DSD), apart from medical disease, is a psychosocial stigma to not only the patient but also their whole family. We present the case of a 24-year-old 46XX, raised as male, with ambiguous genitalia and cyclical hematuria with normal female internal genitalia and secondary sexual characteristics. This case underscores the influence of social stigma and the psychosocial vulnerability associated with DSD on individuals’ lives in developing countries.

Psychological support for individuals with differences of sex development (DSD)

ObjectiveCongenital conditions with atypical development of chromosomal, gonadal, or anatomic sex characteristics are referred to as Differences of Sex Development (DSD). Psychosocial care is recommended to be an integral part of clinical management for individuals with DSD. Few studies have examined the perceived need for, utilization of and the opinions of individuals with DSD regarding psychological support. MethodsThis cross-sectional study was part of a European multicentre study in 14 different medical centres in six countries. In total, 1040 individuals with DSD participated in a patient-reported outcome questionnaire asking about experiences and opinions regarding psychological support in DSD care. ResultsA majority of the participants reported that they had not received psychological support, in childhood and/or adolescence (70.6%, n = 692) nor in adulthood (67.9%, n = 661). Need for psychological support in childhood and/or adolescence was reported by 51.3% (n = 503), need for psychological support in adulthood, was reported by 49.5% (n = 482). The majority (80.2%; n = 718) agreed with the statement that people with DSD should always be offered psychological support. According to 78.7% (n = 697) of the participants, parents of children with DSD should always be offered psychological support. ConclusionOur findings support the existing consensus that psychological support should be an integral part of DSD care. The discrepancy between received and perceived need for psychological support suggests that individuals with DSD experience barriers to access mental health care services. Psychosocial and psychological services for children, adolescents and adults should therefore be available and offered throughout the lifespan to individuals with DSD.

Clinical characteristics and surgical treatment of children with 45, X/46, XY differences of sex development

This study retrospectively analyzes the clinical data of 18 children with 45,X/46,XY differences of sex development (DSD), summarizes their clinical features and explores gonadal and Müllerian duct remnants surgical treatment methods. The clinical data of 18 children with karyotype 45,X/46,XY diagnosed in the Department of Urology of Hunan Children's Hospital from March 2011 to October 2021 were collected. All children underwent HCG stimulation testing, laparoscopic exploration, urethroscopy and bilateral gonadal biopsy. After DSD multidisciplinary team (MDT) meeting, some children underwent gonadectomy and genitalia reconstructive surgeries. The median age at first diagnosis was 1 year and 4 months (range: 10 months ∼ 16 years and 3 months). 5 children presented with female gender; they all maintained their gender assignment. The external masculinisation score (EMS) of patients raised as female was 1 (0∼3) [median (range)]. 13 children presented with male gender, 10 maintained a male gender, 3 were assigned a neutral gender. The EMS of the children raised as male was 5 (2-8) [median (range)], the EMS of the children raised as neutral gender was 4 (3.5-9.5) [median (range)]. The HCG stimulation test was positive in 11 cases, partially positive in 2 case, and negative in 5 cases. There was no relationship between the percentage of chimerism (45X ratio) and the appearance and severity of genital abnormalities. (t=-1.08, P=0.298). There was 1 case of complete gonadal dysgenesis (CGD), 10 cases of mixed gonadal dysgenesis (MGD), 5 cases of partial gonadal dysgenesis (PGD), 1 case of bilateral normal testes and 1 case of ovotesticular DSD (split-lateral type). No gonadal specimen showed germ cell tumor changes. Five cases selected to maintain the female gender, among which 3 cases underwent bilateral gonadectomy and genitalia reconstructive surgeries. Among the 10 children who chose to maintain the male gender, unilateral streak gonadectomy was performed in 4 (57.1%) with MGD, unilateral dysgenetic orchiectomy in 1 (25%) with PGD, and right ovariectomy in 1 with OTDSD. Nine of them underwent genitalia reconstructive surgeries. Four of them preserved their uterus and vagina did not have any complications during the follow-up period. Hypospadias combined with cryptorchidism and residual Müllerian duct structures is the most common phenotype of children with 45, X/46, XY DSD. Mixed gonadal dysgenesis (MGD) is the most common gonadal type. Gender assignment should be carefully selected after a thorough evaluation, while genitalia reconstructive surgery can be considered in selected patients. In children who choose the male gender, the Müllerian duct can be preserved.

Prenatal DEHP exposure induces lifelong testicular toxicity by continuously interfering with steroidogenic gene expression.

Epidemiologic studies suggested the association between prenatal di-(2-ethylhexyl) phthalate (DEHP) exposure and disorders of sex development (DSD), adult male disorders, and reproductive aging. Inhibiting testosterone synthesis by interfering with steroidogenic gene expression induces testicular toxicity, however, whether prenatal DEHP exposure induces testicular toxicity through this mechanism remains uncertain. C57BL/6JGpt male mice underwent different doses (0, 100, 500, 1,000 mg/kg) of prenatal DEHP exposure during gestational day 10 to delivery day, the testicular toxicity (genital development, testosterone, semen quality, and morphology of testis tissue) in the neonatal, post-puberal and middle-aged stages was observed, and the steroidogenic gene (Lhcgr, Star, Cyp11a1, Cyp17a1, Hsd17b3, and Hsd3b2) expression was analyzed by quantitative polymerase chain reaction (qPCR) and Western blot (WB). The interference of steroidogenic gene expression in TM3 cells after mono-(2-ethylhexyl) phthalate (MEHP) exposure was also explored for verification. Prenatal DEHP exposure induced immediate testicular injury in the neonatal stage [reduced anogenital distance (AGD) and intratesticular testosterone], DSD in the post-puberal stage (poor genital development), and reproductive aging in the middle-aged stage (obesity, reduced testosterone and semen quality, and atrophic seminiferous tubules), especially in the high dose. Prenatal DEHP exposure continuously interfered with steroidogenic gene expression (Hsd3b2, Hsd17b3) in RNA and protein levels. MEHP inhibited testosterone synthesis of TM3 cells by interfering with steroidogenic gene expression (Hsd3b2, Hsd17b3) in RNA and protein levels. Prenatal DEHP exposure induces lifelong testicular toxicity by continuously interfering with steroidogenic gene expression, thus indicating the association between prenatal exposure and DSD, adult male disorders, and reproductive aging.

Detection of Molecular Variations at Androgen Receptor Gene in 46,XY Differences in Sex Development Cases.

One of the common causes of 46,XY differences in sex development (DSD) cases is androgen insensitivity syndrome. This X-linked recessive inherited condition is associated with pathological variations of the AR gene, leading to defects in androgen action. Affected 46,XY infants or individuals experience variable degrees of undervirilization and those with severe form will have female-like external genitalia. Therefore, they were more likely assigned and reared as females. The confirmatory molecular test is often needed due to similar clinical manifestations with other conditions causing 46,XY DSD. Since in our country, the molecular test for the AR gene is lacking, the study is conducted as a preliminary study to elaborate on the possibility of developing a molecular test for the AR gene in 46,XY DSD cases. Archived DNAs of 13 46,XY DSD cases were analyzed using polymerase chain reaction and direct sequencing for molecular defects in the AR gene. Clinical and hormonal data were collected and analyzed. The study successfully amplified and visualized the eight exons of the AR gene and revealed two subjects carrying AR gene variants at exon 7. In the first case, 1.2-year-old boy carried heterozygous p.Gln825Arg, which has never been reported elsewhere, and the second subject, a 2.1-year-old girl with heterozygous p.Arg841His. Both subjects presented with severe undervirilization of external genitalia with external genitalia masculinization scores (EMS) of 1.5 and 3. In this series, two of 13 46,XY DSD cases carried variants at the AR gene, resulting in complete androgen insensitivity syndrome.

Intersex in the USA’s Best-Selling Undergraduate Psychology Textbooks: Uneven Critique in an Ongoing Scientific and Ethical Crisis

The field of intersex studies is advancing and requires scholars to update their knowledge and representation of people with intersex variations. To examine how psychology students are taught about people with intersex variations, we reviewed best-selling USA psychology textbooks in introductory psychology (n = 8), psychology of women and gender (n = 5), human sexuality (n = 4), and biological psychology (n = 3). All textbooks indexed intersex or cognate terms, with alternative terms (e.g., disorders of sex development) indexed less frequently. Intersex variations were described as emerging during the stages of sex development, and as challenging binary categories for sex. Several specific variations were commonly described as syndromes with little reference to psychological research or lived experiences. Women and girls with congenital adrenal hyperplasia (CAH) were most clearly framed as “natural experiments” about how nature and nurture intersect. Diverse sex development involving 46 XY genotypes tended to be described as difference from norms for male endosex development. However, two textbooks included lengthy narratives of people’s lived experiences as intersex, and photographs of intersex-identified individuals were common. Photo images of the South African athlete Caster Semenya depicted more of her body than did the photo images of other intersex-identified individuals. The textbooks generally included critical reflection on the assumptions of a gender binary, and on the attribution of ambiguity to others’ bodies, genetic determinism, the medical gaze, and the sex testing of athletes. We consider how information in these textbooks can shape the representation of intersex among psychology students, and how it may be used to develop more humanizing representations of intersex across all psychology textbooks.

The Jacobs Syndrome: Clinical Case

This work describes a clinical case of a violation of sex formation in a newborn child with Y-chromosome dysomy. The diagnostic challenges related to Y-chromosome variability and associated anomalies in sex development are being considered. The work presents clinical and laboratory data for Y-chromosome dysomy. It is noted that the challenge in diagnosing disorders of sex development is associated with the polymorphic clinical manifestations of this syndrome. It is noted that the presence of Y-chromosome dysomy is one of the most common chromosomal abnormalities, ranking third after Down syndrome and Klinefelter syndrome. It is often found that this pathology results in anomalies in genital development. A Y-chromosome polysomy is associated with variable phenotypic manifestations in gonadal development disorders.

Value of the human chorionic gonadotropin stimulation test in the diagnosis of disorder of sexual development in children

To investigate the value of the human chorionic gonadotropin (hCG) stimulation test in the diagnosis of disorder of sexual development (DSD) in children. A retrospective analysis was conducted on 132 children with DSD. According to the karyotype, they were divided into three groups: 46,XX group (n=10), 46,XY group (n=87), and sex chromosome abnormality group (n=35). The above groups were compared in terms of sex hormone levels before and after hCG stimulation test, and the morphological manifestation of the impact of testicular tissue on the results of the hCG stimulation test was analyzed. There was no significant difference in the multiple increase of testosterone after stimulation among the three groups (P>0.05). In the 46,XY group, the children with 5α-reductase type 2 deficiency had a testosterone-to-dihydrotestosterone ratio higher than that of the 46,XY DSD children with other causes. Morphological analysis showed that DSD children with testicular tissue demonstrated a significantly higher multiple increase in testosterone after stimulation compared to children without testicular tissue (P<0.05). The hCG stimulation test has an important value in assessing the presence and function of testicular interstitial cells in children with different types of DSD, and it is recommended to perform the hCG stimulation test for DSD children with unclear gonadal type.

DHX37 Variant Is One of the Common Genetic Causes in Japanese Patients with Testicular Regression Syndrome/Partial Gonadal Dysgenesis without Müllerian Derivatives

Introduction: The testicular regression syndrome (TRS) is a form of differences of sex development (DSD) in which the testes differentiate and function during early embryonic development, but subsequently regress. The clinical phenotype of TRS often overlaps with that of partial gonadal dysgenesis (PGD). Previous studies have demonstrated a causal association between TRS/PGD and heterozygous missense variants of DHX37. Methods: We enrolled 11 Japanese 46,XY individuals (from 10 families) with TRS/PGD who exhibited undetected or hypoplastic testes, Müllerian duct regression, and low serum testosterone or anti-Müllerian hormone levels. The subjects underwent targeted sequencing of 36 known causative genes for DSD, PCR-based Sanger sequencing of DHX37, or whole-exome sequencing. Results: Previously described pathogenic variants or novel nonsense variants (SRY, NR5A1, and DMRT1) were observed in four out of 10 families. Additionally, we identified two heterozygous rare variants of DHX37 in four families: a previously reported pathogenic variant (c.923G>A, p.Arg308Gln) in three and a novel likely pathogenic variant (c.1882A>C, p.Thr628Pro) in one. The external genitalia of patients with the DHX37 variants varied from female-type to male-type without micropenis. Eighty percent of Japanese patients with TRS/PGD had monogenic disorders including DHX37 variant being the most commonly identified (40%). The external or internal genital phenotype of TRS/PGD overlaps between DHX37 variant carriers and others. Conclusions: DHX37 variant is one of the common genetic causes in Japanese patients with TRS/PGD without Müllerian derivatives. Genetic test is helpful in detecting DHX37-related TRS/PGD because of the phenotypic diversity of the external genitalia in this disorder.

Overview of gender-affirming surgery.

This publication will discuss the diversity of procedures that are common to those with intersex traits,/differences of sex development (I/DSD), and transgender and gender diverse (TGD) patients. It will address how these procedures are performed, and common after care and long-term considerations which are relevant to the pediatric radiologist. Some surgeries offered to these patient populations have shared surgical approaches and radiographic considerations. With the growth of TGD procedures as a field, more pediatric subspecialties are performing these procedures, and the approaches are informing the surgical care of the growing number of I/DSD individuals who are seeking surgery in adolescence and young adulthood. Surgeries discussed will include procedures to masculinize or feminize breast/chest tissue, facial bony contours, as well as internal and external genital structures. Patients are diverse and this includes their embodiment goals. As such, not all TGD and I/DSD patients will desire to undergo these procedures. It is important for radiologists to have a foundational understanding of this heterogenous set of procedures so they can provide optimal care for these patient populations.

46, XX disorder of sexual development associated with mixed germ cell tumor of the prostate: a rare case report

BackgroundExtragonadal germ cell tumors originating from the prostate are exceptionally rare. To the best of our knowledge, there have been no reported cases of mixed germ cell tumors in individuals with 46 XX disorder of sex development. In this study, we conducted a comprehensive analysis using whole genome sequencing to investigate the clinicopathological and molecular genetic characteristics of a submitted case, with the objective of elucidating its underlying pathogenesis.Case presentationA 40-year-old male patient was diagnosed with a combination of 46, XX disorder of sex development and a primary prostate mixed germ cell tumor with yolk sac tumor and teratoma components. Whole-genome sequencing revealed that the tumor cells had a high somatic mutational load. Analysis of genomic structural variations and copy number variants confirmed the patient's karyotype as 46, XX (SRY +). Additionally, the patient exhibited short stature, small bilateral testes, slightly enlarged breasts, elevated serum alpha-fetoprotein concentrations, elevated follicle-stimulating hormone and luteinizing hormone levels, and low testosterone levels.DiscussionA case of 46, XX disorder of sex development, along with a primary prostatic mixed germ cell tumor, was diagnosed. This diagnosis has contributed to advancing our understanding of the genetic and phenotypic profile of the disease and may provide some insights for its treatment.

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.

WT1-related disorders: more than Denys-Drash syndrome.

Historically, specific mutations in WT1 gene have been associated with distinct syndromes based on phenotypic characteristics, including Denys-Drash syndrome (DDS), Frasier syndrome (FS), Meacham syndrome, and WAGR syndrome. DDS is classically defined by the triad of steroid-resistant nephrotic syndrome (SRNS) onset in the first year of life, disorders of sex development (DSD), and a predisposition to Wilms tumor (WT). Currently, a paradigm shift acknowledges a diverse spectrum of presentations beyond traditional syndromic definitions. Consequently, the concept of WT1-related disorders becomes more precise. A genotype-phenotype correlation has been established, emphasizing that the location and type of WT1 mutations significantly influence the clinical presentation, the condition severity, and the chronology of patient manifestations. Individuals presenting with persistent proteinuria, with or without nephrotic syndrome, and varying degrees of kidney dysfunction accompanied by genital malformations should prompt suspicion of WT1 mutations. Recent genetic advances enable a more accurate estimation of malignancy risk in these patients, facilitating a conservative nephron-sparing surgery (NSS) approach in select cases, with a focus on preserving residual kidney function and delaying nephrectomies. Other key management strategies include kidney transplantation and addressing DSD and gonadoblastoma. In summary, recent genetic insights underscore the imperative to implement individualized, integrated, and multidisciplinary management strategies for WT1-related disorders. This approach is pivotal in optimizing patient outcomes and addressing the complexities associated with these diverse clinical manifestations.

European Academy of Paediatrics statement on the clinical management of children and adolescents with gender dysphoria.

Gender issues have become a polarised and political subject in modern paediatrics and indeed, in broader society. These include the management of infants with disorders of sex development and transgender sports participation, but especially recently regarding the management of gender dysphoria. The European Academy of Paediatrics (EAP) acknowledges that there are deeply held beliefs about this issue based on conscience and social norms. Several European countries, led by the UK, have recently reviewed the management of gender dysphoria in children and young people. Recognising the need for far more research into treatments such as pubertal suppression and cross-sex hormones in children and young people, we review the current ethical and legal dilemmas facing children with gender dysphoria, their families and the clinical teams caring for them. We suggest an approach that maintains the child's right to an open future whilst acknowledging that the individual child is the crucial person affected by decisions made and must receive appropriate support in decision-making and care for any associated mental health or psychological issues. Noting that national approaches to this vary and are in flux, the EAP advocates a child-centred individual rights-based analytical approach.

A massive alteration of gene expression in undescended testicles of dogs and the association of KAT6A variants with cryptorchidism

Cryptorchidism is the most common form of disorder of sex development in male dogs, but its hereditary predisposition is poorly elucidated. The gonadal transcriptome of nine unilaterally cryptorchid dogs and seven control dogs was analyzed using RNA-seq. Comparison between the scrotal and inguinal gonads of unilateral cryptorchid dogs revealed 8,028 differentially expressed genes (DEGs) (3,377 up-regulated and 4,651 down-regulated). A similar number of DEGs (7,619) was found by comparing the undescended testicles with the descended testicles of the control dogs. The methylation status of the selected DEGs was also analyzed, with three out of nine studied DEGs showing altered patterns. Bioinformatic analysis of the cDNA sequences revealed 20,366 SNP variants, six of which showed significant differences in allelic counts between cryptorchid and control dogs. Validation studies in larger cohorts of cryptorchid (n = 122) and control (n = 173) dogs showed that the TT genotype (rs850666472, p.Ala1230Val) and the AA genotype in 3'UTR (16:23716202G>A) in KATA6, responsible for acetylation of lysine 9 in histone H3, are associated with cryptorchidism (P = 0.0383). Both the transcript level of KAT6A and H3K9 acetylation were lower in undescended testes, and additionally, the acetylation depended on the genotypes in exon 17 and the 3'UTR. Our study showed that the massive alteration of the transcriptome in undescended testicles is not caused by germinal DNA variants in DEG regulatory sequences but is partly associated with an aberrant DNA methylation and H3K9 acetylation patterns. Moreover, variants of KAT6A can be considered markers associated with the risk of this disorder.

A Pilot Survey of Indian Stakeholders: Parents, Doctors, and Grown-Up Patients of Disorders of Sexual Differentiation on Management Decisions and Associated Gender Dysphoria.

Of late, there are many legal representations from select quarters to halt all medical interventions in children with differences of sex development (DSD). In this survey on management decisions in DSD, we distil the views of Indian stakeholders: parents, physicians, and grown-up patients with DSD on their management decisions to identify decisional satisfaction or gender dysphoria. The survey domains included the patient demographics, final diagnosis, decision on the sex of rearing, surgical interventions, opinion of the stakeholders on the preferred age of sex assignment, final sex of rearing, and agreement/disagreement about sex assignment (gender dysphoria). A total of 106 responses were recorded (66% parents, 34% grown-up patients aged 12-50 years). Among parents, 65/70 (95%) preferred the sex to be assigned soon after birth. All grown-up patients preferred sex to be assigned soon after birth. Regarding decisions on surgery, 74% of physicians and 75% of the grown-up patients felt parents should be allowed to decide interventions. Among Indian parents, 90% felt they should have the right to decide surgery in the best interest of their child for a safe social upbringing. Overall, gender dysphoria among Indian DSD patients was <1% (1/103, 0.97%). The predominant preference and opinion of major Indian stakeholders (physicians, parents, and grown-up DSD patients) support the existing approach toward DSD management, including early sex assignment and necessary medical intervention.

A Risk of Gonadoblastoma in Familial Swyer Syndrome—A Case Report and Literature Review

A complete gonadal dysgenesis (CGD) with 46,XY karyotype is known as the Swyer syndrome and belongs to the group of 46,XY differences of sex development (DSD). The main problem in patients with Swyer syndrome is the delayed puberty and primary amenorrhea. Moreover, intrabdominal dysgenetic gonads in the patient with genetic material of a Y chromosome may conduce to the development of gonadal tumors, such as gonadoblastoma or germinoma. The management of such patients is based on preventive excision of dysgenetic gonads and long-term hormonal replacement therapy. Sporadic cases are considered more common than familial cases. This paper presents two siblings with Swyer syndrome in whom gonadoblastoma was found. A thorough review of familial CGD with 46,XY DSD in the literature from the last 15 years suggests that the risk of gonadal tumors could be increased in familial compared to sporadic cases (66.6% vs. 15–45%, respectively).

Analysis of Gender Assignment and Gender Transition in Chinese Patients with Disorders of Sex Development

Background: For individuals with DSD, the decision of gender assignment at birth is a challenging one and the incidence of gender dysphoria in adulthood is much higher than that in the general population.

Novel co-occurrence of hypophosphatemic rickets with 46XY DSD (disorder of sex development) due to a CYP17A1 variant

17-α-hydroxylase deficiency causes a rare type of congenital adrenal hyperplasia (CAH). X-linked hypophosphatemic rickets (XLH) is a rare disorder caused by inactivating mutations in the PHEX gene. We report a novel co-occurrence of XLH with 46XY disorder of sex development due to 17-α-hydroxylase deficiency. A young child reared as a girl, presented as a toddler with genu varus, low phosphorus, normal calcium, and parathormone, and was treated as hypophosphatemic rickets. In early childhood, due to short stature and hypertension, the child was investigated for Turner syndrome. Ultrasound revealed intra-abdominal gonads and an absent uterus. The karyotype was 46XY. Investigations revealed low serum cortisol, renin, normal 17-hydroxyprogesterone, and aldosterone. A year later, a bilateral orchidectomy was performed. Two years later, she was referred to us for further management. Adrenocorticotrophic hormone (ACTH), cortisol, renin, deoxycorticosterone, and clinical exome were advised. She was lost to follow-up for 3 years. On follow-up in early adolescence, she was pre-pubertal; biochemical findings of hypophosphatemic rickets, elevated ACTH, low cortisol, and low normal aldosterone were noted. Clinical exome revealed variants in the CYP17A1 gene (homozygous) causing CAH (17-α-hydroxylase) and PHEX (hemizygous) gene causing XLH. Treatment with hydrocortisone, phosphate, cholecalciferol, and calcitriol was commenced. Hypertension is now well-controlled, but genu varus persists and may require surgical correction.

Disorders of sexual development in small ruminants

Intersex conditions, also known as disorders of sexual development (DSD), are uncommon in small ruminants. This report describes in detail, 2 cases of DSD in small ruminants, including clinical presentation, histopathological and cytogenetic analysis that led to the final diagnoses. Case 1, a mixed-breed ewe, was assessed due to a reported ram-like behavior at ~ 6 months of age. Physical examination revealed abnormal external genitalia with enlarged clitoris and bilateral inguinal gonads, histologically confirmed as testicular tissue. Karyotyping revealed sex chromosome blood chimerism (54XX, 54XY), implicating freemartinism as the cause of DSD. Case 2 was a 1-year Nigerian Dwarf cryptorchid male goat presented for castration. During surgery, bilateral ovoid gonads attached to a bicornuate uterus were identified. Histology revealed testicular tissue and uterus alongside vas deferens were consistent with persistent Müllerian duct syndrome. This report describes presentations, findings, and features of DSD, a rare occurrence in small ruminants.