Disorders Of Sexual Differentiation Research Articles

Systematic review and meta-analysis comparing outcomes following orchidopexy for cryptorchidism before or after 1 year of age.

BackgroundCurrent guidelines recommend orchidopexy for cryptorchidism by 12 months of age, yet this is not universally adhered to. The aim of this systematic review and meta‐analysis was to compare outcomes between orchidopexies performed before and after 1 year of age.MethodsMEDLINE and Embase were searched (September 2015) using terms relating to cryptorchidism, orchidopexy and the outcomes of interest. Studies were eligible for inclusion if they compared orchidopexy at less than 1 year of age (early) with orchidopexy at 1 year or more of age (delayed) and reported the primary outcome (testicular atrophy) or one of the secondary outcomes (fertility potential, postoperative complication, malignancy). Studies were excluded when more than 50 per cent of infants had intra‐abdominal testes, or the population included infants with disorders of sexual differentiation. Additional studies were identified through reference list searching. Unpublished data were sought from the ORCHESTRA study investigators.ResultsFifteen eligible studies were identified from 1387 titles. There was no difference in atrophy rate between early orchidopexy and delayed orchidopexy (risk ratio 0·64, 95 per cent c.i. 0·25 to 1·66; 912 testes). Testicular volume was greater (mean difference 0·06 (95 per cent c.i. 0·01 to 0·10) ml; 346 testes) and there were more spermatogonia per tubule (mean difference 0·47 (0·31 to 0·64); 382 testes) in infants undergoing early orchidopexy, with no difference in complication rate (risk ratio 0·68, 0·27 to 1·68; 426 testes). No study reported malignancy rate.ConclusionAtrophy and complication rates do not appear different between early and delayed orchidopexy, and fertility potential may be better with early orchidopexy. Imprecision of the available data limits the robustness of these conclusions.

Hernia uteri inguinalis in ovotesticular disorder of sexual differentiation: A rare complication and role of imaging.

Neonate with ambiguous genitalia can cause great apprehension for the family as well as for healthcare providers. We report a rare complication of delayed diagnosis of hernia uteri inguinalis in ovotesticular disorder of sexual differentiation (DSD) in 20-year-old male patient who presented with pain and swelling in left inguinal region since 1 month. He had a past surgical history of repair of hypospadias 10 years back. On imaging, the left inguinal hernia sac contained nonfunctioning uterus and one ovary in the left scrotal sac and one testis in the right scrotal sac. Further investigation confirmed genotypically female (46XX) with negative sex determining region-Y gene on fluorescence in situ hybridization. The patient was given psychiatric counseling and wished to remain as male. The left inguinal hernia was repaired with excision of nonfunctioning uterus, ovary, and fallopian tube. Hernia uteri inguinalis is rare complication seen in DSD with only three cases being reported worldwide thus far, including our case.

Contribution of the Medical Imaging in Care of Ambiguous Genitalia

We report a case of ambiguous genitalia in a 15-year-old patient to demonstrate input of medical imaging in the diagnosis and care of this rare congenital deformation. Disorders of sexual differentiation (DSD) have been defined as congenital conditions in which development of chromosome, gonad, or anatomic sex is atypical and that raise an issue in the sex assignment. In lower socioeconomic countries where antenatal diagnosis is almost non-existent, due to lack of technical facilities, their medical and surgical management is hard. The case which we report was investigated by ultrasonography and genitography, which remains primary indications in our context.

Coexistence of Trisomy 13 and SRY (−) XX Ovotesticular Disorder of Sex Development

ABSTRACTIntroduction: Ovotesticular disorder of sex development (OT-DSD) is a rare disorder of sexual differentiation characterized by the presence of both testicular and ovarian tissue in an individual and the majority of cases have been reported with 46,XX karyotype. In 46,XX cases, testicular differentiation may occur due to the translocation of SRY to the X chromosome or to an autosome. Case report: Herein, we present a female newborn with a combination of trisomy 13 and SRY (-) XX OT-DSD. Conclusion: Trisomy 13 is a relatively common and well-known chromosomal disorder in which disorders of sexual differentiation are not frequent. In the absence of SRY, overexpression of pro-testis genes, or decreased expression of pro-ovarian/anti-testis genes have been suggested as underlying mechanisms of testicular formation. The findings in this patient were suggestive of an underlying genomic disorder associated with FGF9 and/or SPRY2.

Utilidad clínica de la medición de la hormona antimülleriana en niños

La hormona antimülleriana, inicialmente denominada sustancia inhibitoria mülleriana, es una glicoproteína homodimérica de 12,5 kDa, que pertenece a la familia del factor de crecimiento transformante beta (TGF-β) y desempeña un papel crucial en la diferenciación sexual masculina al favorecer la regresión de los conductos de Müller. Dado que su producción en el varón es principalmente por las células de Sertoli inmaduras, en las últimas décadas ha crecido su utilidad más allá de la evaluación de la función ovárica y tratamientos de fertilidad en las mujeres, lo que ha permitido evaluar en el varón la función testicular y los estados de hipogonadismo, trastornos de la diferenciación sexual, pubertad patológica, criptorquidia, entre otras condiciones clínicas revisadas en este manuscrito. Además, esta revisión describe el rol fisiológico de la hormona antimülleriana en los testículos prepuberales y las pruebas de laboratorio disponibles para su medición.

The prostatic utricle: An under-recognized condition resulting in significant morbidity in boys with both hypospadias and normal external genitalia

Pediatric presentations of a prostatic utricle have received only scant attention. Though recognized with increased frequency in boys with hypospadias, little is described about their incidence and potential for morbidity in boys with normal external genitalia. We initially reviewed a cohort of 64 patients with hypospadias seen over a 3-year period to determine the frequency of investigative lower urinary tract studies and utricle identification. Children with disorders of sexual differentiation were excluded from this review. A subsequent group of 70 boys with hypospadias and 23 boys with normal external genitalia presenting with lower urinary tract symptoms (LUTS) who were found to have an unsuspected utricle were reviewed. This comparative group was investigated since symptomatology was the indication for evaluation, contrasting with those in the hypospadias group who were investigated because of hypospadias presence alone. In our initial review of 64 patients only 24 (37.5%) underwent an investigative study and six (9.4%) had a utricle. Three (50%) required surgical excision, allowing their hypospadias repair to proceed. Results in the subsequent group with hypospadias confirmed these findings with increased rates of investigation and identification. The boys with normal external male genitalia all required surgery since symptoms were the result of the utricle alone. Penile pain with voiding, hematuria, epididymitis, and urinary infection were the most common causes for interventions. The prostatic utricle should be considered as a cause of morbidity in boys with both normal external genitalia and those with hypospadias. Endoscopic or radiological evaluation (see Figure) should be undertaken in all boys with proximal hypospadias, boys with hypospadias and associated cryptorchidism, and those with hypospadias with associated urinary symptoms. Boys with normal external genitalia with lower urinary tract symptoms not explained with imaging should undergo cystoscopy, as an unidentified unsuspected utricle may be the underlying cause.

A review of paediatric and adolescent gynaecology services in a tertiary outpatient clinic

Adolescence is a distinctive stage in human development during which many simple and complex medical conditions can present for the first time. Paediatric and adolescent gynaecological conditions need careful multidisciplinary clinical management with a sensitive approach understanding the patients’ psychological and physiological circumstances. The objective of this study is to review the tertiary paediatric and adolescent gynaecology service in Leeds, United Kingdom and to present an overview of the various conditions that present to such a clinic. A total of 985 patients were seen over a 16-year period and the increasing number of patients seen over this time establishes the need for such a service to exist. Complex developmental anomalies of the genital tract and disorders of sexual differentiation formed a major portion of the referrals. Presence of a significant number of referrals for simple gynaecological conditions including menstrual irregularities, gynaecological pain, vulvovaginitis, polycystic ovary syndrome and concerns about labial appearance indicates the reluctance of general gynaecologists and general practitioners to manage such conditions in young patients. This emphasizes the need for continued education of primary health care professionals and establishment of clear guidelines and care pathways for the management of this special patient group.

Normative penile anthropometry in term newborns in Kumasi, Ghana: a cross-sectional prospective study

BackgroundGenital measurements are a useful adjunct in the early detection of various endocrine conditions including hypopituitarism and disorders of sexual differentiation. Standards for genital sizes have been published but racial/ethnic differences exist. This study was done to establish norms for genital sizes in term Ghanaian male newborns.MethodsThis was a cross-sectional study of all apparently well full-term newborns of postnatal age < 48 h and birth weight between 2.5 and 4.0 kg delivered at Komfo Anokye Teaching Hospital within the study period. Anthropometric and genital parameters were documented for study subjects as well as parental socio-demographic indices.ResultsA total of 644 male newborns were recruited between May and September 2014. The mean penile length (MPL) was 3.3 ± 0.5 cm and the mean penile width (MPW) was 1.05 ± 0.1 cm. An inverse relationship was found between maternal age and MPL (correlation coefficient −0.062, 95% CI −0.121 to −0.002; p = 0.04). MPL was also significantly different (p = 0.04) by mode of delivery, with babies delivered by caesarean section having the lowest MPL. MPL correlated positively with both gestational age (p = 0.04) and birth length (p < 0.001), while MPW correlated proportionally with birth weight and length (p < 0.001 for both).ConclusionsUsing the conventional definition of micropenis as stretched penile length (SPL) < 2.5 standard deviation (SD) below the mean and macropenis as an SPL > 2.5 SD, a Ghanaian term newborn may warrant investigation if he has an MPL < 2.1 cm or > 4.4 cm.

46, XX Male or Ovotesticular DSD (SRY-negative) without SRY, is it Possible to have Testicular Tissues?

The 46, XX male syndrome, or the 46, XX testicular Disorder of Sexual Differentiation (DSD) is rare. We report a clinical case of a male infant 46, XX, DSD with SRY negative. This observation suggests that genes other than SRY play an important role in determining sex. From this case we will present a review of the literature to take stock of the subject.

Female megalourethra with imperforate anus: A rare presentation

Congenital megalourethra is a rare form of functional obstructive uropathy caused by dysgenesis of the penile corpora cavernosa and spongiosa. Megalourethra is usually described in males and rarely seen in disorders of sexual differentiation. A neonate presented to us with ambiguous genitalia, a megalourethra and imperforate anus. Genetically, the baby was 46XX and the presence of mullerian structures was confirmed during laparotomy. Hormonal workup for congenital adrenal hyperplasia was negative. Although the functional obstruction of the urethra was circumvented by a suprapubic cystostomy, the status of the upper tracts ultimately decided the fate of the child. The presence of crossed fused ectopia with dysplasia and hydronephrosis led to multiple bouts of urosepsis and rapid renal failure. Evaluation of renal as well as other systemic abnormalities is essential for prognosis and planning of treatment.

PERSISTENT MULLERIAN DUCT SYNDROME PRESENTING AS AN INGUINAL HERNIA : A CASE REPORT

A brief report of persistent mullerian duct syndrome (PMDS) with 46XY karyotype which is one of the rarest variety of disorders of sexual differentiation (DSD) accounting only 5% cases of all is being presented. A 21 years old male with left inguinal hernia and absent right testis presented in surgical outdoor and was operated. On exploration female genital organs like uterus and fallopian tubes along with contralateral testis were present in left inguinal canal as a content of sliding left inguinal hernia.

Disorders of Sexual Differentiation: A study on the Incidence and Types of Female Pseudo Hermaphrodites

Disorders of Sexual Differentiation: A study on the Incidence and Types of Female Pseudo Hermaphrodites

MINI-INVASIVE SURGERY IN THE FIRST THREE YEARS OF LIFE

&lt;em&gt;Background&lt;/em&gt;: In the last 30 years mini-invasive surgery (MIS) has been widely used becoming an important and irreplaceable method, safe and highly reliable, in both the diagnostic and therapeutic treatment, for a variety of conditions in both the child and the newborn. This has led to a significant increase of the use of this approach in the pediatric population under the age of 3 years, with results similar to the open techniques. &lt;br /&gt;&lt;em&gt;Materials and Methods:&lt;/em&gt; At the Department of Surgery, Medicine and Neuroscience at the University of Siena we conducted a retrospective study of patients aged less than three years of life underwent minimally invasive procedures. The clinical information was extrapolated from a prospective database. They included all patients treated from June 2003 to October 2014. Were considered for each patient demographics, associated diseases, surgical procedure, MIS approach, the instruments used, the duration of surgery and hospitalization, intraoperative and postoperative complications (early and late). &lt;br /&gt;&lt;em&gt;Results&lt;/em&gt;: From a total of 933 minimally invasive procedures, 150 (16%) were performed under the age of 3 years. The 76% of patients were males, 24% were females. Twenty-two patients (15%) presented associated diseases. 53 (35%) were diagnostic procedures, 97 (65%) were therapeutic procedures. We treated: 1 3 esophageal atresia, 1 diaphragmatic hernia, 1 congenital cystic adenomatoid malformation (CCAM), 8 stenosis of the ureteropelvic junction , 2 disorders of sexual differentiation (DSD), 20 inguinal hernias, 75 cases of non-palpable testis, 15 cases of Hirschsprung disease, 10 cases of fundoplication, 4 cases of ovarian tumors, 6 cases of nephrectomy, 4 cases of eminefrectomy and 1 case of thymoma. In total we performed 6 (4%) thoracoscopic procedures, 18 (12%) in retroperitoneoscopy and 126 (84%) in laparoscopy. 55 procedures (37%) were performed in "one-trocar" technique. Among the remaining 95 (67%), in 62 (41%) we used a “3 mm” instruments, in 18 (12%) “5 mm” instruments and in 15 (14%) they were mixed (3/5 mm). The duration of the procedure was an average of 59 minutes (range: 20-135 minutes) in diagnostic procedures and 184 minutes (range: 40-370 minutes) in the therapeutic procedures. We converted to an open technique in 14/150 (9%). We reported no postoperative complication and incidentaloma no intraoperative complications. The following is 100% survival. &lt;br /&gt;&lt;em&gt;Conclusions&lt;/em&gt;:MIS is probably the most important change that has taken place in the field of Pediatric Surgery in the last 30 years. The optimum benefits are to be found in the lesser surgical stress, the lower cavity contamination, the magnification of details, the reduced hospital stay, reduced morbidity or the best aesthetic result.

A rare case of infertility - SRY positive, 46,XX testicular disorder of sexual differentiation

Aim To highlight the complexity of infertility causes by describing the rare case of a man with a testicular disorder of sexual differentiation. Diagnosis A 33 years old Caucasian male presented with a 3-year-old history of primary infertility. His investigations revealed a low testosterone and a raised LH and FSH levels. A sample sent for sperm analysis revealed azoospermia. Chromosomal analysis and karyotyping revealed a 46 XX SRY positive karyotype. Treatment The patient was initiated on testosterone replacement and on calcium/vitamin D supplements. Conclusion Fertility evaluation requires complex assessments and a broad knowledge of possible causes.

Sex differences in autism: a resting-state fMRI investigation of functional brain connectivity in males and females.

Autism spectrum disorders (ASD) are far more prevalent in males than in females. Little is known however about the differential neural expression of ASD in males and females. We used a resting-state fMRI-dataset comprising 42 males/42 females with ASD and 75 male/75 female typical-controls to examine whether autism-related alterations in intrinsic functional connectivity are similar or different in males and females, and particularly whether alterations reflect 'neural masculinization', as predicted by the Extreme Male Brain theory. Males and females showed a differential neural expression of ASD, characterized by highly consistent patterns of hypo-connectivity in males with ASD (compared to typical males), and hyper-connectivity in females with ASD (compared to typical females). Interestingly, patterns of hyper-connectivity in females with ASD reflected a shift towards the (high) connectivity levels seen in typical males (neural masculinization), whereas patterns of hypo-connectivity observed in males with ASD reflected a shift towards the (low) typical feminine connectivity patterns (neural feminization). Our data support the notion that ASD is a disorder of sexual differentiation rather than a disorder characterized by masculinization in both genders. Future work is needed to identify underlying factors such as sex hormonal alterations that drive these sex-specific neural expressions of ASD.

A Case Report on Ovotesticular DSD

Abstract True hermaphrodite (TH) is one of the rarest varieties of disorders of sexual differentiation (DSD). It refers to individuals who have both ovarian tissue and testicular elements regardless of their karyotype. The development of phenotypic sex is a complex process dependent upon the differentiation of bipotential gonads into the testes or ovaries. In the nature and location of the gonads true hermaphroditism may be bilateral (testis and ovary or ovotestes on each side), unilateral (ovotestes on one side and testis or ovary on the other), or lateral existence (testis on one side and ovary on the other). Additionally, the ovotestes is defined as a single gonad containing both testicular and ovarian tissues. In the present report the authors describe a case of ambiguous genitalia in an 18 year old who had come for laparoscopic hysterectomy; the sex of the patient was determined to be male before making the final diagnosis. Early and appropriate gender assignment is necessary for healthy physical and psychologic development of children with ambiguous genitalia. Gender assignment can be facilitated with a team approach that involves a pediatric endocrinologist, geneticist, urologist, psychiatrist, social worker, neonatologist, nurse, and radiologist, allowing timely diagnosis and proper management.

Pediatric laparoscopic surgery in North-Central Nigeria: Achievements and challenges

Background and Objective: Advances in laparoscopy are making the service accessible even in resource-poor countries where adaptations are made to meet local challenges. We report our experience in the provision of laparoscopy service to children at a tertiary health center in North-central Nigeria. Methods: A team of pediatric surgeons, anesthetists, and nurses collaborated to provide service and train other personnel. A prospective collection of data on biodata, diagnoses, procedure, and outcome over an effective period of 36 months of laparoscopy intervention of the 54 months between September 2009 and February 2014 was done. Consent, which also included the possibility of conversion to open was obtained from the parents of the patients. Results: A total of 73 patients aged 2 weeks to 16 years with a male: female ratio of 3 to 1 had laparoscopy done during the period. Fifty-two (71.2%) procedures were therapeutic, and 21 (28.8%) cases were done as emergency. Laparoscopic appendectomy was the most commonly performed procedure 25 (34.3%), followed by laparoscopic orchidopexy 17 (23. 3%), and diagnostic laparoscopy for disorders of sexual differentiation in 13 (17.8%). The length of stay in hospital postoperative was 1-3 days with a mean of 1.34 ΁ 0.45 days. The complications recorded included hemorrhage, in a case of infantile hypertrophic pyloric stenosis due to failed electrocautery, one port site burns injury from diathermy dissection, and two periport pain postoperation. There was no mortality recorded. Conclusion: Pediatric laparoscopic service is gaining recognition in our practice in spite of poor resources, incessant industrial actions, and apathy from support staff. The outcomes are encouraging as the patients had minimal morbidities. Skills are improved through practice and retraining and manpower, and instruments are being expanded through our collaboration and training.

Profile of patients with genitourinary anomalies treated in a clinical genetics service in the Brazilian unified health system

ObjectiveTo describe the profile of patients with genitourinary abnormalities treated at a tertiary hospital genetics service. MethodsCross-sectional study of 1068 medical records of patients treated between April/2008 and August/2014. A total of 115 cases suggestive of genitourinary anomalies were selected, regardless of age. A standardized clinical protocol was used, as well as karyotype, hormone levels and genitourinary ultrasound for basic evaluation. Laparoscopy, gonadal biopsy and molecular studies were performed in specific cases. Patients with genitourinary malformations were classified as genitourinary anomalies (GUA), whereas the others, as Disorders of Sex Differentiation (DSD). Chi-square, Fisher and Kruskal–Wallis tests were used for statistical analysis and comparison between groups. Results80 subjects met the inclusion criteria, 91% with DSD and 9% with isolated/syndromic GUA. The age was younger in the GUA group (p<0.02), but these groups did not differ regarding external and internal genitalia, as well as karyotype. Karyotype 46,XY was verified in 55% and chromosomal aberrations in 17.5% of cases. Ambiguous genitalia occurred in 45%, predominantly in 46,XX patients (p<0.006). Disorders of Gonadal Differentiation accounted for 25% and congenital adrenal hyperplasia, for 17.5% of the sample. Consanguinity occurred in 16%, recurrence in 12%, lack of birth certificate in 20% and interrupted follow-up in 31% of cases. ConclusionsPatients with DSD predominated. Ambiguous genitalia and abnormal sexual differentiation were more frequent among infants and prepubertal individuals. Congenital adrenal hyperplasia was the most prevalent nosology. Younger patients were more common in the GUA group. Abandonment and lower frequency of birth certificate occurred in patients with ambiguous or malformed genitalia. These characteristics corroborate the literature and show the biopsychosocial impact of genitourinary anomalies.

Timing and Outcome Concerns regarding Feminizing Genitoplasty from the Perspective of Egyptian Families of Girls with Virilized External Genitalia

Background: Congenital adrenal hyperplasia in females leads to virilization of external genitalia and persistent urogenital sinus. There are controversies regarding the timing and outcomes of surgery. Deferring surgeries beyond childhood is difficult to implement in conservative societies, and may result in stigmatization and distress to individuals with disorders of sexual differentiation and their families. Methods: Thirty girls with virilization due to congenital adrenal hyperplasia were admitted for single-stage feminizing genitoplasty, between 2011 and 2014. We prospectively studied the concerns and input of the families represented by the mothers. After comprehensive counselling, the mothers completed a questionnaire to clarify their priorities and concerns related to surgery. Results: Surgeries were performed at a mean age of 22 months. Most cases ranged between Prader's degrees III and IV. Egyptian families believe that early surgical reconstruction is in the best interest of their girls. They are marginally more concerned about functional outcomes and future child bearing than external appearance and cosmetic outcomes. Conclusions: Social difficulties noticeably add challenges to the management plan within conservative societies. Early genital reconstructive surgery, when reasonably indicated, needs to remain a viable option. Comprehensive psychosocial support within a multidisciplinary approach is needed to defer feminizing genitoplasty in selected cases to adolescence.

Concepts and Updates in the Evaluation and Diagnosis of Common Disorders of Sexual Development.

Our understanding of disorders of sexual differentiation (DSD) has evolved from aberrations of human genital development to a broad group of complex disorders of etiological and functional significance. The unique challenge of DSD conditions is that they create a cause for significant angst and concern for both parents and physician, as they frequently lead to questions with regards to gender assignment, surgically corrective options, long-term outlook regarding gender identity, and reproductive potential. To further add to the burden, many patients who present with genital abnormalities do not have a clear explanation as to the underlying basis of their disorder. This review looks at DSD from a pediatric urology point of view with emphasis on evaluation, diagnosis, and algorithm for work-up. We also discuss novel genetic analysis techniques and their value in diagnosis. Overall, this is an all-encompassing review on a diagnostic approach to DSD, with inclusion of recent developments and controversies, which will benefit urologists and other physicians alike.