[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.

One-stage surgical case management of a two-year-old Arabian horse affected by male-pseudo hermaphroditism.

A two-year-old Arabian horse presented for abnormal external genitalia and dangerous stallion-like behavior was diagnosed with disorder of sexual development (DSD), also known as intersex/hermaphroditism. Standing 1-stage surgical procedure performed under sedation, and local anesthesia to concurrently eliminate stallion-like behavior, risk of neoplastic transformation of intraabdominal gonads, and to replace ambiguous external genital with a functional, and cosmetically more acceptable anatomy. Step-1) Laparoscopic abdominal exploration and gonadectomy; Step-2) Rudimentary penis resection and perineal urethrostomy. The horse tolerated surgery well (combined surgery time 185 min) with no complications. At macroscopic examination of the gonads, they resembled hypoplastic testis-like tissues. Microscopic examination confirmed presence of seminiferous tubules, Leydig and Sertoli/granulosa cells. Cytogenetic evaluation revealed a 64,XX karyotype, SRY-negative. The stallion-like behavior subsided within days post-operatively. Long-term follow-up revealed the genitoplasty site healed without urine scalding or urethral stricture. The owner satisfaction was excellent and the horse could be used post-surgery as an athlete.

[Clinical, genetic, and pathological analysis in 165 children with disorders of sex development]. / 165ä¾‹å„¿ç«¥æ€§å‘è‚²å¼‚å¸¸ç–¾ç— çš„ä¸´åºŠã€é—ä¼ å­¦ä¸Žç— ç†å­¦åˆ†æž.

OBJECTIVES: To investigate the clinical phenotypes, genetic characteristics, and pathological features of children with disorders of sex development (DSD). METHODS: A retrospective analysis was conducted on epidemiological, clinical phenotype, chromosomal karyotype, gonadal pathology, and genotype data of 165 hospitalized children with DSD at Children's Hospital of Hebei Province and Tangshan Maternal and Child Health Hospital from August 2008 to December 2022. RESULTS: Among the 165 children with DSD, common presenting symptoms were short stature (62/165, 37.6%), clitoromegaly (33/165, 20.0%), cryptorchidism (28/165, 17.0%), hypospadias (24/165, 14.5%), and skin pigmentation abnormalities/exteriorized pigmented labia majora (19/165, 11.5%). Chromosomal karyotype analysis was performed on 127 cases, revealing 36 cases (28.3%) of 46,XX DSD, 34 cases (26.8%) of 46,XY DSD, and 57 cases (44.9%) of sex chromosome abnormalities. Among the sex chromosome abnormal karyotypes, the 45,X karyotype (11/57, 19%) and 45,X/other karyotype mosaicism (36/57, 63%) were more common. Sixteen children underwent histopathological biopsy of gonadal tissues, resulting in retrieval of 25 gonadal tissues. The gonadal tissue biopsies revealed 3 cases of testes, 3 cases of dysplastic testes, 6 cases of ovaries, 11 cases of ovotestes, and 1 case each of streak gonad and agenesis of gonads. Genetic testing identified pathogenic/likely pathogenic variants in 23 cases (23/36, 64%), including 12 cases of 21-hydroxylase deficiency congenital adrenal hyperplasia caused by CYP21A2 pathogenic variants. CONCLUSIONS: Short stature, clitoromegaly, cryptorchidism, hypospadias, and skin pigmentation abnormalities are common phenotypes in children with DSD. 45,X/other karyotype mosaicism and CYP21A2 compound heterozygous variants are major etiological factors in children with DSD. The most commonly observed gonadal histopathology in children with DSD includes ovotestes, ovaries, and testes/dysgenetic testes.

A Rare Case of Precocious Puberty in a Child with a Novel GATA-4 Gene Mutation: Implications for Disorders of Sex Development (DSD) and Review of the Literature.

BACKGROUND: Disorders/Differences of sex development (DSD) are often due to disruptions of the genetic programs that regulate gonad development. The GATA-4 gene, located on chromosome 8p23.1, encodes GATA-binding protein 4 (GATA-4), a transcription factor that is essential for cardiac and gonadal development and sexual differentiation. CASE DESCRIPTION: A child with a history of micropenis and cryptorchidism. At 8 years of age, he came under our observation for an increase in sexual pubic hair (pubarche). The laboratory parameters and the GnRH test suggested a central precocious puberty (CPP). Treatment with GnRH analogs was started, and we decided to perform genetic tests for DSD. The NGS genetic investigation showed a novel and heterozygous variant in the GATA-4 gene. DISCUSSION: In the literature, 26 cases with 46,XY DSD due to the GATA4 gene were reported. CONCLUSION: The novel variant in the GATA-4 gene of our patient was not previously associated with DSD. This is the first case of a DSD due to a GATA-4 mutation that develops precocious puberty. Precocious puberty could be associated with DSD and considered a prelude to hypogonadism in some cases.

Diagnostic challenges and management advances in cytochrome P450 oxidoreductase deficiency, a rare form of congenital adrenal hyperplasia, with 46, XX karyotype.

Cytochrome P450 oxidoreductase deficiency (PORD) is a rare form of congenital adrenal hyperplasia that can manifest with skeletal malformations, ambiguous genitalia, and menstrual disorders caused by cytochrome P450 oxidoreductase (POR) mutations affecting electron transfer to all microsomal cytochrome P450 and some non-P450 enzymes involved in cholesterol, sterol, and drug metabolism. With the advancement of molecular biology and medical genetics, increasing numbers of PORD cases were reported, and the clinical spectrum of PORD was extended with studies on underlying mechanisms of phenotype-genotype correlations and optimum treatment. However, diagnostic challenges and management dilemma still exists because of unawareness of the condition, the overlapping manifestations with other disorders, and no clear guidelines for treatment. Delayed diagnosis and management may result in improper sex assignment, loss of reproductive capacity because of surgical removal of ruptured ovarian macro-cysts, and life-threatening conditions such as airway obstruction and adrenal crisis. The clinical outcomes and prognosis, which are influenced by specific POR mutations, the presence of additional genetic or environmental factors, and management, include early death due to developmental malformations or adrenal crisis, bilateral oophorectomies after spontaneous rupture of ovarian macro-cysts, genital ambiguity, abnormal pubertal development, and nearly normal phenotype with successful pregnancy outcomes by assisted reproduction. Thus, timely diagnosis including prenatal diagnosis with invasive and non-invasive techniques and appropriate management is essential to improve patients' outcomes. However, even in cases with conclusive diagnosis, comprehensive assessment is needed to avoid severe complications, such as chromosomal test to help sex assignment and evaluation of adrenal function to detect partial adrenal insufficiency. In recent years, it has been noted that proper hormone replacement therapy can lead to decrease or resolve of ovarian macro-cysts, and healthy babies can be delivered by in vitro fertilization and frozen embryo transfer following adequate control of multiple hormonal imbalances. Treatment may be complicated with adverse effects on drug metabolism caused by POR mutations. Unique challenges occur in female PORD patients such as ovarian macro-cysts prone to spontaneous rupture, masculinized genitalia without progression after birth, more frequently affected pubertal development, and impaired fertility. Thus, this review focuses only on 46, XX PORD patients to summarize the potential molecular pathogenesis, differential diagnosis of classic and non-classic PORD, and tailoring therapy to maintain health, avoid severe complications, and promote fertility.

Expanding the reproductive organ phenotype of CHD7-spectrum disorder.

CHD7 disorder is a multiple congenital anomaly syndrome with a highly variable phenotypic spectrum, and includes CHARGE syndrome. Internal and external genital phenotypes frequently seen in CHD7 disorder include cryptorchidism and micropenis in males, and vaginal hypoplasia in females, both thought to be secondary to hypogonadotropic hypogonadism. Here, we report 14 deeply phenotyped individuals with known CHD7 variants (9 pathogenic/likely pathogenic and 5 VOUS) and a range of reproductive and endocrine phenotypes. Reproductive organ anomalies were observed in 8 of 14 individuals and were more commonly noted in males (7/7), most of whom presented with micropenis and/or cryptorchidism. Kallmann syndrome was commonly observed among adolescents and adults with CHD7 variants. Remarkably, one 46,XY individual presented with ambiguous genitalia, cryptorchidism with Müllerian structures including uterus, vagina and fallopian tubes, and one 46,XX female patient presented with absent vagina, uterus and ovaries. These cases expand the genital and reproductive phenotype of CHD7 disorder to include two individuals with genital/gonadal atypia (ambiguous genitalia), and one with Müllerian aplasia.

Phenotypic Variation in 46,XX Disorders of Sex Development due to the Fourth Zinc Finger Domain Variant of WT1: A Familial Case Report.

INTRODUCTION: The variants in the zinc finger (ZF) domains 1-3 in WT1 are one of the major causes of 46,XY disorders of sex development (DSD). Recently, variants in the fourth ZF (ZF4 variants) were reported to cause 46,XX DSD. However, all the 9 patients reported were de novo, and no familial cases were identified. CASE PRESENTATION AND RESULTS: The proband (16-year-old social female) had a 46,XX karyotype with dysplastic testes and moderate virilization in genitalia. A ZF4 variant, p.Arg495Gln, in WT1 was identified in the proband, her brother, and mother. The mother did not show any virilization with normal fertility, and the 46,XY brother developed normal puberty. CONCLUSION: The phenotypic variations due to the ZF4 variant are extremely broad in 46,XX cases.

Disorders of sex development: Challenges in a low-resource country.

AIM: We aimed to identify the challenges in the management of sexual development abnormalities in a low-resource country. METHODS: The study was retrospective from January 2000 to December 2017 based on patient records from two pediatric surgery departments. Epidemiological, clinical, paraclinical, treatment, and outcome data were studied. RESULTS: We collected data on 13 patients (average age = 7.95 years). The sex of rearing was as follows: three females (23%), 10 males (77%). Atypical genitalia other than hypospadias represented the reason for consultation in 92% of the cases. We could not find complete hormonal analyses; testosterone levels were studied in 69.23% of cases. We found the following disorders of sexual development (DSD): four patients with 46,XX karyotype (30.77%), eight patients with 46,XY karyotype (61.53%), and one patient with 46,XX/XY karyotype. Four patients had medical treatment only, four had surgical treatment only, and one patient had medical and surgical treatment. The medical treatment comprised topical administration of androgen. The surgical treatment consisted of feminizing genitoplasty for one patient and masculinizing genital surgeries for two patients. Six of the 13 patients were lost to follow-up. CONCLUSION: The socioeconomic difficulties of the population and the lack of access to basic diagnostic and paraclinical methods, coupled with the negative cultural representations of the pathology, constitute the challenges in the management of DSD in our practice.

Up-to-Date Clinical and Biochemical Workup of the Child and the Adolescent with a Suspected Disorder of Sex Development.

BACKGROUND: The suspicion of a disorder of sex development (DSD) often arises at birth, when the newborn presents with ambiguous genitalia, or even during prenatal ultrasound assessments. Less frequently, the aspect of the external genitalia is typically female or male, and the diagnosis of DSD may be delayed until a karyotype is performed for another health issue, or until pubertal age when a girl presents with absence of thelarche and/or menarche or a boy consults for gynaecomastia and/or small testes. SUMMARY: In this review, we provide a practical, updated approach to clinical and hormonal laboratory workup of the newborn, the child, and the adolescent with a suspected DSD. We focus on how to specifically address the diagnostic approach according to the age and presentation. KEY MESSAGE: We particularly highlight the importance of a detailed anatomic description of the external and internal genitalia, adequate imaging studies or surgical exploration, the assessment of reproductive hormone levels - especially testosterone, anti-Müllerian hormone, 17-hydroxyprogesterone, and gonadotropins - and karyotyping.

[The clinical characteristics and treatment of children with disorders of sex development and early prevention of their siblings].

Disorders of sex development (DSD) is a class of diseases characterized by discordant phenotypes of sex chromosome karyotypes, gonads and external genitalia. The etiology is complex and the clinical manifestations are varied. Understanding the clinical characteristics of patients with various types of DSD help make accurate etiological diagnosis and prepare individualized treatment plans according to the etiology (including sex assignment, endocrine hormone replacement, surgery and fertility protection, etc.). Due to the increased risk of DSD in the second pregnancy of the parents of DSD patients, early preventive measures such as pre-pregnancy genetic counseling and prenatal diagnosis during pregnancy can effectively avoid or reduce the risk of DSD in their siblings.

Sexual Developmental Disorders in Pediatrics.

Abstract: Disorders of sex development (DSD) are a heterogeneous group of pathologies that result in an alteration in sex determination or differentiation. DSD are estimated to affect 1: 4,500 newborns and according to the 2006 Chicago Consensus classification, DSD can be divided into three categories: those with a 46 XX karyotype, those with a 46 XY karyotype and those relating to sex chromosomes. It is crucial to correctly identify the pathology already in the first days of life to direct the patient and his family to the best path of care. For this reason, the role of the pediatrician is fundamental in the correct identification of the clinical picture and in supporting the family during the long process that involves the management of these patients. To make a diagnosis, it is necessary to follow a path led by a multidisciplinary team that includes several steps such as the execution of the genetic analysis, the evaluation with diagnostic imaging methods and laboratory evaluations. The therapeutic management, on the other hand, is still very complex even if in recent years we have moved from an attitude of early gender reassignment to an approach of watchful waiting to let the patient choose when she/he is mature enough to do so, which gender she/he feels to belong. It should not be forgotten that throughout this process the pediatrician must be both supportive and clinically active in the management of the child and his family.

SOX9 in organogenesis: shared and unique transcriptional functions.

The transcription factor SOX9 is essential for the development of multiple organs including bone, testis, heart, lung, pancreas, intestine and nervous system. Mutations in the human SOX9 gene led to campomelic dysplasia, a haploinsufficiency disorder with several skeletal malformations frequently accompanied by 46, XY sex reversal. The mechanisms underlying the diverse SOX9 functions during organ development including its post-translational modifications, the availability of binding partners, and tissue-specific accessibility to target gene chromatin. Here we summarize the expression, activities, and downstream target genes of SOX9 in molecular genetic pathways essential for organ development, maintenance, and function. We also provide an insight into understanding the mechanisms that regulate the versatile roles of SOX9 in different organs.

Testicular Sertoli Cell Hormones in Differences in Sex Development.

The Sertoli cells of the testes play an essential role during gonadal development, in addition to supporting subsequent germ cell survival and spermatogenesis. Anti-Müllerian hormone (AMH) is a member of the TGF-ß superfamily, which is secreted by immature Sertoli cells from the 8th week of fetal gestation. lnhibin B is a glycoprotein, which is produced by the Sertoli cells from early in fetal development. In people with a Difference or Disorder of Sex Development (DSD), these hormones may be useful to determine the presence of testicular tissue and potential for spermatogenesis. However, fetal Sertoli cell development and function is often dysregulated in DSD conditions and altered production of Sertoli cell hormones may be detected throughout the life course in these individuals. As such this review will consider the role of AMH and inhibin B in individuals with DSD.

[Clinical and genetic analysis of a child with disorder of sex development].

OBJECTIVE: To report on the diagnosis and treatment process and clinical characteristics of a child with disorder of sex development (DSD) and to conduct pathological, imaging and genetic analysis for the patient. METHODS: Clinical data of the patient were collected. Genetic testing including chromosomal karyotyping, fluorescence in situ hybridization (FISH), copy number variations (CNVs) analysis, SRY gene detection and multiple ligation-dependent probe amplification (MLPA) were carried out. RESULTS: The patient had a social gender of male, with a history of hypospadia and breast development. Sex hormone tests showed slightly raised prolactin. Imaging results showed bilateral breast hyperplasia, abnormal seminal vesicle glands, rudimentary uterus, and underdeveloped right testis. Intraoperative examination revealed that the child had an ovary on the left and a testis on the right. The pathological results showed fibroadenomatoid changes in the breast. The patient had a karyotype of 46,XX. FISH results showed 46,XX.ish(DXZ1x2, SRYx0). Molecular testing showed that NR0B1, PHEX, CXORF21, GJB1, PQBP1, and COL4A5 genes are duplicated. There was a presence of SRY gene and absence of UYT gene. CONCLUSION: DSD should be considered in patients with genital abnormality and male breast development. Ultrasound, sex hormone test and genetic testing should be performed to confirm the diagnosis of DSD, and molecular testing should be performed if necessary. Individualized treatment of DSD patient requires cooperation of multiple clinical disciplines.

Dioecy and chromosomal sex determination are maintained through allopolyploid speciation in the plant genus Mercurialis.

Polyploidization may precipitate dramatic changes to the genome, including chromosome rearrangements, gene loss, and changes in gene expression. In dioecious plants, the sex-determining mechanism may also be disrupted by polyploidization, with the potential evolution of hermaphroditism. However, while dioecy appears to have persisted through a ploidy transition in some species, it is unknown whether the newly formed polyploid maintained its sex-determining system uninterrupted, or whether dioecy re-evolved after a period of hermaphroditism. Here, we develop a bioinformatic pipeline using RNA-sequencing data from natural populations to demonstrate that the allopolyploid plant Mercurialis canariensis directly inherited its sex-determining region from one of its diploid progenitor species, M. annua, and likely remained dioecious through the transition. The sex-determining region of M. canariensis is smaller than that of its diploid progenitor, suggesting that the non-recombining region of M. annua expanded subsequent to the polyploid origin of M. canariensis. Homeologous pairs show partial sexual subfunctionalization. We discuss the possibility that gene duplicates created by polyploidization might contribute to resolving sexual antagonism.

46 XY disorder of sex development (DSD) due to 5 alpha (SRD5A2) deficiency - Experience from a multidisciplinary Pediatric Gender Clinic.

BACKGROUND: SRD5A2 deficiency leads to incomplete masculinization of individuals with a 46 XY karyotype. A definitive diagnosis in early infancy facilitates decisions concerning choice of sex of rearing and management. AIM: To review the clinical presentation, diagnosis, treatment and outcome of children with 46 XY DSD due to SRD5A2 deficiency at a Paediatric Gender Clinic. STUDY DESIGN AND METHODS: Retrospective review of cases of SRD5A2 deficiency (2000-15) managed with a standard protocol at a multidisciplinary clinic. Demographic data, clinical presentation, physical findings, investigations (hormonal profile, imaging, genitoscopy), psychological evaluation (child, family), medical and surgical management, outcome and follow up were collated and analyzed. RESULTS: There were 12 cases aged 3 days-14 years at presentation, 3 had parental consanguinity. Eight were reared as males and 4 as females. Specialist referral was sought for hypospadias (5), atypical genitalia (5) or incongruent pubertal masculinization (2). All had chordee, symmetrical inguinoscrotal gonads, rugose labioscrotum and proximal hypospadias (perineoscrotal -9, perineal -3). Both pubertal cases had significant masculinization and no gynecomastia. The median testosterone/dihydrotestosterone ratio was 22.1(IQR-8.6-55.7). Despite a classical phenotype, four (2 prepubertal, 2 pubertal) had a ratio <10. Genitoscopy showed urogenital sinus remnant (4) and hypoplastic verumontanum (5). Sex reassignment was done in 4. Surgical management was staged and completed by 4 years in those with infantile presentation. Besides correction of chordee and urethroplasty in 11, other procedures included orchidopexy (5), excision of a urogenital sinus remnant (4) and correction of penoscrotal transposition (4). The urethroplasty was single staged in 3. All operated cases were followed up (mean age at last follow up - 10.63 years, mean follow up period - 7.25 years). The overall cosmetic result was satisfactory, but the phallic structure remained relatively small across prepubertal period. Uroflowmetry curves were normal in 9. All showed penile tumescence/erection and two peripubertal cases had typical secondary sexual characters. All cases, including those with sex reassignment, have a well-adjusted male psyche. DISCUSSION AND CONCLUSION: The diagnosis, management and longitudinal follow up of cases of SRD5A2 deficiency at a multidisciplinary gender clinic is presented. Diagnostic dilemmas with low T/DHT ratios remained in a third of cases. Most were diagnosed in infancy and assigned a male sex of rearing, all underwent staged masculinizing genitoplasty. Those with sex reassignment also fared well with comprehensive management after family counseling.

46, XY Disorders of Sexual Development: a case report and theoretical framework.

BACKGROUND AND AIM: Disorders of sexual differentiation (DSD) with karyotype 46,XY include gonadal developmental differences such as complete gonadal dysgenesis, partial gonadal dysgenesis, testicular regression and ovotesticular sexual differentiation disorder, differences in androgen synthesis or action, such as androgen synthesis deficiency, androgen action deficits, LH receptor deficiency, AMH synthesis or action deficits, and other conditions such as severe hypospadias, cloaca estrophy, etc. Methods: A 17 years-old girl came to our attention for hirsutism, clitoral hypertrophy, primary amenorrhea, and bilateral mammary hypoplasia. According to clinical features and anamnesis, the diagnosis of 46, XY DSD was made. For diagnostic purposes, she underwent an extensive genetic analysis, hormone dosage and instrumental examinations. After a clitoridoplasty and hormone replacement treatment, the patient performs appropriate multidisciplinary follow-up and regular psychotherapy. RESULTS: The clinical case reported falls, according to the recent classification developed by the Chicago Consensus, within the scope of DSD with karyotype 46, XY. About 160 cases of patients with 17ß-HSD3 deficiency, diagnosed at a mean age of 12 years, are described in the literature, most of them coming from Western Asia and Europe and only three cases from Eastern Asia. Clinically, about 30% of patients showed virilization, 20% clitoromegaly, ambiguous genitalia, inguinal/labial mass, 16% primary amenorrhea, and 5% absence of mammary development, features that are partly traced in the case described here. CONCLUSIONS: This case underscores the complexity of managing individuals with DSD. Having acquired the concept that irreversible surgery should be avoided, except in cases where failure to do so would determine health risks, the primary objective of the medical decision lies in meeting conditions aimed at harmonious sexual identification, especially regarding sexual activity and fertility, involving a team of experienced professionals (psychologists, pediatricians, surgeons, endocrinologists, radiologists), capable of promptly identifying suggestive clinical signs.

Disorders of sexual development in the cat: Current state of knowledge and diagnostic approach.

PRACTICAL RELEVANCE: Any congenital or developmental abnormality of any part of the male or female reproductive tract is a 'disorder of sexual development' (DSD). The tricolored male cat phenotype, cryptorchidism, gonadal hypoplasia and incidental abnormalities such as cystic remnants or embryonic ducts are well-known feline DSDs. CLINICAL CHALLENGES: Full characterization of DSDs requires sex chromosome determination and identification of genes related to development of the gonads, internal tubular genitalia and external genitalia. Fortunately, affected cats are seen sporadically and the clinical effects are usually minimal. CLASSIFICATION: The classification nomenclature has changed. In place of intersex, hermaphrodite, pseudohermaphrodite and sex reversal, the newer standard classification, based on sex chromosomes, designates sex chromosome DSD when there is an abnormality in the sex chromosomes, and XX (female) and XY (male) DSDs where there is not. Identification of the gonadal type (testes, ovaries, ovotestes or gonadal dysgenesis) and documentation of the internal and external genital components completes the classification. EVIDENCE BASE: The original basis of the DSD classification was a consensus reached in humans. It was quickly accepted in veterinary pathology, courtesy of its logic and ease of application, and it has subsequently begun to appear in peer-reviewed papers and clinical reviews. This article reviewing the various disorders in cats is based on application of the classification and draws on the feline peer-reviewed literature encompassing chromosome analysis and definition of reproductive abnormalities, syndromes and diseases.

Gonadal tumor and malignancy in 118 patients with disorders of sex development with Y chromosome.

OBJECTIVE: To provide more information about tumor prevalence and malignant transformation among patients with disorders of sex development (DSD) for further guidance in prophylactic gonadectomies and surveillance. METHODS: SPSS software (version 20.0) was used for all statistical analyses. RESULTS: Phenotypically female DSD patients with a Y chromosome have a higher risk of gonadal malignancy. CONCLUSION: Bilateral gonadal resection is recommended as soon as diagnosis is made for phenotypically female patients with disorders of sex development with a Y chromosome.

Masculinizing surgery in disorders/differences of sex development: clinician- and participant-evaluated appearance and function.

OBJECTIVES: To report the long-term follow-up outcomes of masculinizing surgery in disorders/differences of sex development (DSD), including both physicians' and patients' perspectives on appearance and functional outcome, including sexuality. PATIENTS AND METHODS: In total, 1040 adolescents (age ≥16 years) and adults with a DSD took part in this multicentre cross-sectional clinical study in six European countries in 2014/2015. Of those, 150 living in other than the female gender had some kind of masculinizing surgery: hypospadias repair, orchidopexy, breast reduction and/or gonadectomy. The study protocol included medical data collection, an optional genital examination, and patient-reported outcomes including satisfaction with appearance and current sexual functioning. RESULTS: Diagnoses included partial and mixed gonadal dysgenesis (45,XO/46,XY; n = 38), Klinefelter syndrome/46,XX males (n = 57), and various 46,XY DSDs (n = 42; e.g. partial androgen insensitivity syndrome, severe hypospadias) and 13 with other diagnoses. Of the participants, 84 underwent hypospadias surgery, 86 orchidopexy, 52 gonadectomy and 32 breast reduction (combinations possible). Physicians evaluated anatomical appearance at genital examination as poor in approximately 11% of patients. After hypospadias surgery, 38% of participants reported that they were (very) dissatisfied with anatomical appearance and 20% with function. The physician and patient evaluations were moderately correlated (r = 0.43). CONCLUSION: The majority of participants were neutral to satisfied with the appearance and function in the long-term after masculinizing surgery. Given the initial severe phenotype and a risk of unsatisfactory results after masculinizing surgery in DSD, treatment should be handled by experienced multidisciplinary teams in order to optimize the postoperative results.