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The enthusiasms on 'intersex' have been with humanity since antique. Inadequacies in the management of the condition backwash in Psychosocial and medical morbidities with occasional mortality. The upsurge in the knowledge of its pathophysiology over generations has incredibly improved the management outcome. This study aims to present the fundamentals of the Pathophysiology and Management of DSD. The information provided is intended to guide in the basic evaluation and care of individuals with the disorder. Material and Method: Search from PubMed, EMBASE and AJOL for Literature on Disorders of Sexual development was reviewed. The search words were: intersex, the disorder of sexual differentiation (DSD), Pseudohermaphroditism, Hermaphroditism and Ambiguous genitalia. The literature on the Pathophysiology and the managementwas appraised and summarized. Conclusion: Genetic inquest and advances in molecular biology had provided cognizance on the pathophysiology of DSD. Patient's advocacy groups and de novo medical ethics necessitated the transformations in the approach to the management

Background: In congenital adrenal hyperplasia (CAH) with ambiguous genitalia, assigning gender of rearing can be complex, especially If genitalia is highly virilized. Apart from karyotype, prenatal androgen exposure, patient's gender orientation, sociocultural, and parental influences play a role. The aim of this study was to assess gender dysphoria and psychosocial issues in patients of CAH raised as males and females. Materials and Methods: This is a cross-sectional study that includes patients (old and new) with CAH who were treated by us in the last 6 months. A semi-structured interview proforma was used to elicit history and psychosocial background of the patients. The clinical and biochemical details were noted. For psychological analysis, patients were screened for gender dysphoria using Parent Report Gender Identity Questionnaire for children

Background and Objectives: 46 XY disorders of sexual development (DSD) cover a wide spectrum of phenotypes ranging from unambiguous female genitalia to ambiguous male genitalia with hypospadias or dysgenetic gonads. Management of these patients depends on the cause of DSD, degree of feminization, age at presentation, and gender orientation. The aim of this study was to evaluate the presentation and management of patients with 46XY DSD at our center. Patients and Methods: All new and old patients of 46XY DSD attending the endocrine OPD in a period of 16 months were included in this study. Clinical, cytogenetic, hormonal, and radiological evaluation were done to identify the cause of DSD. Results: Among 19 patients, eight were diagnosed with disorders of gonadal development (one with complete gonadal dysgenesis, four with partial gonadal dysgenesis, two with congenital bilateral anorchia, and one with ovotesticular DSD) and eight with disorders of androgen synthesis and action (one with complete androgen insensitivity syndrome [AIS], three with partial AIS and four with 5α reductase deficiency). In three patients, a definitive diagnosis could not be made. Conclusions: Management of patients with DSD depends on etiology, gender assignment, gender orientation, hormonal treatment, genital surgery, and consequent psychosocial implications. Due to the overlapping clinical and biochemical parameters in different subsets of DSD, only a preliminary etiological diagnosis can be made in some cases. Genetic studies with long-term follow-up are required for an accurate diagnosis.

Cutis marmorata telangiectatica congenita (CMTC) is an uncommon, congenital, vascular malformation first described by van Lohuizen in 1922. CMTC is an infrequently reported congenital cutaneous disorder and is usually present at birth but can appear up to 3 months to 2 years of age. Hereby, we report a case of a 2-day-old infant with CMTC involving trunk with rarely reported congenital anomaly involving multiple system, i.e., musculoskeletal, cardiovascular, pulmonary, ophthalmic, excretory, oropharyngeal, and reproductive system. [ABSTRACT FROM AUTHOR]

The Mirena intrauterine device (IUD) is a hormone-secreting contraceptive device. Pregnancy with the Mirena is rare and effects to the fetus are unknown. Here we present four females with genital virilization after pregnancy with persistent Mirena IUD. All patients had a 46, XX karyotype and normal hormone evaluation. All underwent exam under anesthesia, demonstrating posterior labial fusion and short urogenital sinus with normal bladder, urethra, vagina, and cervix. Three of four patients underwent flap vaginoplasty without complications and good cosmetic outcomes. This series suggests that persistent levonorgestrel-secreting IUD during pregnancy is associated with genital virilization in female fetuses. [ABSTRACT FROM AUTHOR]

Background: Sex determination and differentiation in humans are processes that involve the interaction of several genes such as SRY, SOX9 genes which are important in the development of the male genital system. Also NR5A1 gene plays an important role in the development of gonads and the adrenal glands. Aim of the study include clinical assessment of children with disorders of sex development, molecular analyses for SRY, SOX9 and NR5A1 genes and genetic counseling for the patients and their families. Subjects and methods: This study included sixteen patients from 1 day to 6 years old attending the Genetics and Endocrinology unit, Pediatric department, Faculty of Medicine, Menoufiya University, Egypt. All cases were subjected to: detailed history, thorough clinical examination, routine and hormonal investigations, imaging studies, cytogenetic and molecular studies for SRY, SOX9 and NR5A1 genes. Results: Positive consanguinity between the parents was detected in seven patients (43.75%). Serum 17 OH progesterone was elevated in five patients (31.25%) and below normal ranges in two patients (12.5%). Cytogenetic study revealed six patients with normal (46, XX) karyotype, eight patients with normal (46, XY) karyotype, one patient had (45, X) karyotype and another with (45, X/46, XY) karyotype. Thirteen out of sixteen patients undergone molecular studies, SRY gene was +ve for six patients with normal male (46, XY) undergone and one patient with (45, X) karyotype (translocated SRY). SRY was −ve for five patients with normal female (46, XX) karyotype and one patient with (45, X/46, XY) karyotype (deleted SRY). All patients were +ve for SOX9 and NR5A1 genes and no deletions detected. Conclusion: Genetic studies beside clinical and hormonal evaluation will allow us to rapidly reach a diagnosis and to identify a ‘molecular sex’ for each patient.

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

Abstract Background A rare disorder of sex development is 45,X/46,XY mosaicism, which is phenotypically very heterogenous, ranging from normal male (or female) to that of genital ambiguity of varying degrees. Case We report a case of a neonate with 45,X/46,XY mosaicism and hydrocolpos, and we point out the dilemma and the difficulty in gender assignment. Summary and Conclusion Gender assignment of cases with frank genital ambiguity is often difficult to be determined, because several factors have to be taken into consideration, such as genital appearance, anticipated urological and sexual function, capacity for future fertility, gonadal malignancy risk, and psychosocial factors. A multidisciplinary approach is definitely needed in the management of such cases. [ABSTRACT FROM AUTHOR]

Abstract Study Objective 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. Design Prospective descriptive study. Setting University Teaching Hospital. Participants All children who presented with genital ambiguity. Interventions and Main Outcome Measures 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. Results Fifteen children presented with DSD at a median age of 20 months. 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 7 years. 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 21 months (interquartile range, 2-26 months). Conclusion The frequency of ovotesticular DSD is high in our setting. The decision of sex assignment was finally made at a median age of 7.5 months in most of our patients with satisfactory short-term surgical outcome. [ABSTRACT FROM AUTHOR]

Background: Silver-Russell syndrome (SRS) is characterized by growth retardation and variable features including macrocephaly, body asymmetry, and genital manifestations such as cryptorchidism in 46,XY patients. Case presentation: The patient was born at 39 weeks with a birth weight of 1344 g. Subtle clitoromegaly warranted a thorough evaluation, which disclosed 46,XY karyotype, bilateral undescended testes, and a rudimentary uterus. Because of severe under-virilization, the patient was assigned as female. Failure to thrive, macrocephaly, and body asymmetry led to the diagnosis of SRS, confirmed by marked hypomethylation of H19/IGF2 intergenic differentially methylated region (IG-DMR). From age 9 years, progressive virilization occurred, which necessitated luteinizing hormone-releasing hormone analog (LHRHa) treatment. Gonadal resection at 15 years revealed immature testes with mostly Sertoli-cell-only tubules. Panel analysis for 46,XY-differences of sex development (DSD) failed to detect any pathogenic variants. Conclusions: This is the second reported case of molecularly proven 46,XY SRS accompanied by severe under-virilization. SRS should be included in the differential diagnosis of 46,XY-DSD. [ABSTRACT FROM AUTHOR]

Summary: Objective: The purpose of this narrative review was to summarize available data on testosterone levels in normal, healthy adult males and females, to provide a physiologic reference framework to evaluate testosterone levels reported in males and females with conditions that elevate androgens, such as disorders of sex development (DSD), and to determine the separation or overlap of testosterone levels between normal and affected males and females. Methods: A literature review was conducted for published papers, from peer reviewed journals, reporting testosterone levels in healthy males and females, males with 46XY DSD, and females with hyperandrogenism due to polycystic ovary syndrome (PCOS). Papers were selected that had adequate characterization of participants, and description of the methodology for measurement of serum testosterone and reporting of results. Results: In the healthy, normal males and females, there was a clear bimodal distribution of testosterone levels, with the lower end of the male range being four‐ to fivefold higher than the upper end of the female range(males 8.8‐30.9 nmol/L, females 0.4‐2.0 nmol/L). Individuals with 46XY DSD, specifically those with 5‐alpha reductase deficiency, type 2 and androgen insensitivity syndrome testosterone levels that were within normal male range. Females with PCOS or congenital adrenal hyperplasia were above the normal female range but still below the normal male range. Conclusions: Existing studies strongly support a bimodal distribution of serum testosterone levels in females compared to males. These data should be considered in the discussion of female competition eligibility in individuals with possible DSD or hyperandrogenism. [ABSTRACT FROM AUTHOR]

Purpose Little is known about the phenotypes, diagnoses, and sex of rearing of infants with atypical genital development in the United States. As part of a multicenter study of these infants, we have provided a baseline report from US difference/disorder of sex development clinics describing the diagnoses, anatomic features, and sex of rearing. We also determined whether consensus guidelines are followed for sex designation in the United States. Methods Eligible participants had moderate-to-severe genital atypia, were aged <3 years, and had not undergone previous genitoplasty. Karyotype, genetic diagnosis, difference/disorder of sex development etiology, family history, and sex of rearing were collected. Standardized examinations were performed. Results Of 92 subjects, the karyotypes were 46,XX for 57%, 46,XY for 34%, and sex chromosome abnormality for 9%. The median age at the baseline evaluation was 8.8 months. Most 46,XX subjects (91%) had congenital adrenal hyperplasia (CAH) and most 46,XY subjects (65%) did not have a known diagnosis. Two individuals with CAH underwent a change in sex of rearing from male to female within 2 weeks of birth. The presence of a uterus and shorter phallic length were associated with female sex of rearing. The most common karyotype and diagnosis was 46,XX with CAH, followed by 46,XY with an unknown diagnosis. Phenotypically, atypical genitalia have been most commonly characterized by abnormal labioscrotal tissue, phallic length, and urethral meatus location. Conclusions An increased phallic length was positively associated with rearing male. Among the US centers studied, sex designation followed the Consensus Statement recommendations. Further study is needed to determine whether this results in patient satisfaction. [ABSTRACT FROM AUTHOR]

Aromatase deficiency is a rare autosomal recessive genetic disorder with an unknown incidence. Aromatase converts androgens into estrogen in the gonadal and extra-gonadal tissues. Aromatase deficiency causes ambiguous genitalia in the female fetus and maternal virilization (hirsutism, acne, cliteromegaly, deep voice) during pregnancy due to increased concentration of androgens. A 19 months old girl patient was assessed due to presence of ambiguous genitalia. There were findings of maternal virilization during pregnancy. The karyotype was 46, XX. Congenital adrenal hyperplasia was not considered since adrenocorticotropic hormone, cortisol, and 17-hydroxyprogesterone levels were within normal ranges. At age two months, follicle-stimulating hormone and total testosterone levels were elevated and estradiol level was low. Based on these findings, aromatase deficiency was suspected. A novel homozygous mutation IVS7-2A>G (c.744-2A>G) was identified in the CYP19A1 gene. Pelvic ultrasound showed hypoplasic ovaries rather than large and cystic ovaries. We identified a novel mutation in the CYP19A1 gene in a patient who presented with ambiguous genitalia and maternal virilization during pregnancy. Presence of large and cystic ovaries is not essential in aromatase deficiency. [ABSTRACT FROM AUTHOR]

Objective: Disorders of sex development (DSD) is a nomenclature intended to defeat the discomfort of families and patients and has found worldwide usage. The aim of this study was to address the perception and usage of terminology among the parents of DSD patients in a tertiary center in western Turkey. Methods: The records of the DSD council (multidisciplinary team where each patient with DSD is discussed) between years 2008-2015 were reviewed retrospectively. Data including details of the management process, patient characteristics and follow-up details were noted. Then inquiries reflecting parental perception about terminology were implemented during clinical visits. Results: In total, 121 patients were evaluated in monthly meetings of the DSD council and 79 inquiries were completed. Fifty-one percent of the families admitted knowing the terms DSD, ambiguous genitalia, "dubious genitals" and intersex. However, only 2% preferred using DSD, 6% intersex and 14% ambiguous genitalia. Fifty-two percent of the parents used a disease name in Latin (mostly hypospadias) addressing the disorder. The offspring of 69% of the parents who were familiar with the name "dubious genitals" were diagnosed in the neonatal period. The preferred terminology used by parents was strongly associated with the terminology used most commonly in the medical speciality their child most often attended. Conclusion: Each country has its own social norms. We suggest therefore that local committees including medical professionals, patients and families should be employed to develop proper terminology. [ABSTRACT FROM AUTHOR]

Ambiguous genitalia in the newborn can present a diagnostic challenge in medical practice. In most cases, the causes of genitourinary anomalies are not well understood; both genetic and environmental factors are thought to play a role. In this study, we report mosaic SRY gene deletion identified by fluorescence in situ hybridization (FISH) analysis in three unrelated newborn male patients with genital anomalies. G‐banded chromosomes and microarray analysis were normal for all three patients. One patient had microphallus, hypospadias, bifid scrotum, exstrophic perineal tissue identified as a rectal duplication, lumbar vertebral anomalies, scoliosis, and a dysmorphic sacrum. The other two patients had isolated epispadias with the urethral meatus close to the penopubic junction. All three had bilateral palpable gonads in the scrotum. While this is the first report of mosaic SRY deletions, mosaic SRY sequence variants have been described in patients with variable genitourinary anomalies. This study identifies FISH analysis as a reliable method for mosaic SRY deletion detection. We suggest SRY FISH analysis should be used in the clinical workup of patients with genitourinary ambiguity. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the mid-term results of clitoroplasty through the reduction of the length and diameter of the corpus cavernosum, as well as the volume of the glans. Patients and methods From October 2003 to July 2015, we performed 29 clitoroplasties using the described procedure. The median (range) age of the patients was 18 (3–47) months. After surgery we evaluated the volume of the clitoris, the appearance of glans, and its sensitivity to light touch, pressure, and pain. Results The length of the apparent part of the glans remained large (>10 mm) in four patients (14%), was an average size (between 5 and 10 mm) in 11 (39%), and small (<5 mm) in 13 (46%). The length of the corpus cavernosum was <20 mm and its diameter <5 mm in all cases. The sensitivity of the reduced clitoris to touch, pressure and pain seemed normal in all patients. In addition, we never found the circumflex arteries and nerves of the penis (on histological examination of excised pieces of corpus cavernosum) in all children operated on during the first 3 years of life. The circumflex arteries of the penis begin to develop, only after the fourth year. This anatomical finding is an argument for performing clitoroplasty at an early age to avoid any risk of intraoperative and postoperative bleeding. Conclusions The sensitivity of the clitoral glans appeared to be normal in all cases, with a good cosmetic appearance of the external genitalia in most patients. [ABSTRACT FROM AUTHOR]

Introduction Genital ambiguity is a very common phenomenon in disorders of sex development (DSD). According to the Chicago Consensus 2006, feminizing genitoplasty, when indicated, should be performed in the most virilized cases (Prader III to V). Advances in the knowledge of genital anatomy in DSD have enabled the development and improvement of various surgical techniques. Mobilization of the urogenital sinus (MUS), first described by Peña, has become incorporated by most surgeons. However, the proximity of the urethral sphincter prompts concern over urinary incontinence, especially for full mobilization of the urogenital sinus. Objective To retrospectively evaluate the short-term surgical results of feminizing genitoplasty with total mobilization of the urogenital sinus in patients with DSD. Methods Review of medical records of all patients undergoing feminizing genitoplasty with mobilization of the urogenital sinus. We evaluated the rates of complications from surgery and of urinary incontinence, as well as cosmetic results, according to the opinion of the surgeon and the family. Results A total of 8 patients were included in the study. The mean age at surgery was 51 months. Congenital adrenal hyperplasia (CAH) was diagnosed in six patients, and gonadal dysgenesis in the other two. The vagina was separated from the urethra, with suitable distance in all cases. No patient had urinary incontinence after surgery. The mean follow-up of patients was. 20 months (3–56 months). In all cases, surgeons recorded being satisfied with the aesthetic result of post-surgical genitalia. The family was recorded as satisfied with the aesthetic result of the genitalia after surgery. In every case, there was no need for a second surgical procedure. Conclusion The total mobilization of the urogenital sinus is a feasible and safe technique. The technique permits good cosmetic results, and urinary incontinence is absent. Type of study Therapeutic study. Level of evidence Level III. [ABSTRACT FROM AUTHOR]

Ring chromosome 13 is a rare genetic condition with an incidence of 1/58,000 in live births. Major clinical features of patients with ring chromosome 13 include growth and developmental retardation, microcephaly, facial dysmorphism, ambiguous genitalia, anal atresia, eye malformations, retinoblastoma, and hand, foot, and toe abnormalities. The severity of the phenotype depends on the amount of genetic material lost during ring chromosome formation. Here, we report 2 cases with ring chromosome 13 at either end of the phenotypic spectrum. [ABSTRACT FROM AUTHOR]

Disorders of sexual development (DSD) are a rare but disastrous condition. A plethora of biological, psychological, and ethical problems surround the management of DSD cases. A case of 25-year-old woman with a complaint of primary amenorrhea was presented. She wanted to be examined as she had planned to be married. However, examinations revealed that she had 46, XY karyotype, complete androgen insensitivity syndrome, and vaginal agenesis. After several family meetings, the patient, her family, and her partner decided that she would remain as a woman despite the results. Disorders of sexual development are not only about the biological complexities, but also the psychological, social, and ethical dilemmas faced by both the patient and clinicians. A coordinated care team plays a crucial role in addressing the unique challenges presented by DSD, particularly for those diagnosed later in life. Comprehensive and multidisciplinary approach is essential for managing DSD patients. • Disorders of sexual development (DSD) cases require complex diagnosis and multidisciplinary approach. • The late diagnosis of DSD is associated with a myriad of biological, psychological, and social problems. • Surgical and hormonal interventions regiment and timing remain a topic of debate for clinicians. [ABSTRACT FROM AUTHOR]