Penoscrotal Hypospadias Research Articles

Penoscrotal Transposition: A Case Report

Penoscrotal transposition (PST) is an extremely rare congenital malformation, usually associated with a wide variety of other anomalies. We describe an exceptional case of a newborn with PST, but normal upper urinary tract and no other associated malformations. An unbooked newborn male delivered at term with no reported antenatal complications. There was no evidence of mother being exposed to teratogens during pregnancy. On physical examination, an abnormal appearance of the external genitalia could be seen. There was a complete rotation of the external genitalia with cryptorchidism. Penis with chordee was noted (Fig. 1). Urinalysis, renal and vesical sonography, and voiding cystourethrography showed no other urological abnormalities. There were no associated cardiological or gastrointestinal anomalies. Fig. 1 Complete penoscrotal transposition PST is a very uncommon heterogeneous condition in which the scrotum is positioned superior and anterior to the penis. Less than 20 cases of extreme degree of PST with normal scrotum have been reported in the literature [1]. PST results from abnormal genital tubercle development around the 6th week of gestation. It is associated with delay in the midline fusion of the urethral folds. Although the occurrence of most reported cases of PST has been sporadic, other congenital anomalies such as hypospadias, chordee, and renal agenesis or dysplasia could be found in approximately 90% of patients [2]. Gastrointestinal abnormalities, predominantly imperforate anus, were found in 30% of cases [3]. PST may present with a broad spectrum of abnormalities ranging from simple shawl scrotum (doughnut scrotum) to very complex extreme transposition with cardiac, gastrointestinal, craniofacial, central nervous system, genital, and urological malformations [4]. Growth deficiency and mental retardation have also been noticed in 60% of patients [5]. Differential diagnosis must include pseudohermaphroditism, penoscrotal hypospadias, micropenis, intrauterine penile amputation, and especially penile agenesis with a midline skin tag anterior to the anus. Complete penoscrotal transpositions have been rarely reported in the Indian literature [6]. Surgery in more complex cases of PST is technically challenging. It is usually performed between 12–18 months. The size of the phallus and its potential to develop at puberty into a sexually satisfactory penis are of paramount relevance when surgery is planned. In order to assess this situation, a surgeon must carefully palpate the corporal bodies to determine their bulk and sometimes perform a testosterone test to demonstrate erections. Extreme penoscrotal transposition with severe hypospadias and chordee is difficult to differentiate from penile agenesis with a midline skin tag anterior to the anus (with penile atrophic body buried in the perineum). In both cases the penile reconstruction and repositioning are often unsatisfactory, and female gender reassignment, while ethically controversial, may be a prudent therapeutic in selected cases.

Tubularized Incised Plate Repair for Penoscrotal Hypospadias: Role of Surgeon's Experience

To give a retrospective analysis of factors affecting outcome of tubularized incised plate (TIP) repair for penoscrotal hypospadias. Data of all patients who underwent TIP repair for penoscrotal hypospadias by a single surgeon were retrieved. Follow-up was carried out every 3 months within the first year and annually thereafter. Repairs were divided into 2 groups: Group 1 included surgeries performed in the first 2 years after fellowship training, and group 2 included repairs performed afterward. Chi-square test was used for statistical analysis. Statistical significance was defined as P<.05. Data for 90 patients were retrieved for july 2001 through march 2009: Group 1 included 20 patients and group 2 included 70. The neourethra was covered with spongioplasty in 25 and dartos flap in 65. The overall success rate was 86%. Group 2 patients showed a statistically significant higher success rate of 91% compared with only 65% for group 1. Use of dartos flap was associated with statistically significant higher success (92%) compared with coverage of the neourethra with spongioplasty (68%). In group 1, use of dartos flap was associated with statistically significant better success (82% vs 33%). In group 2 patients, use of dartos flap showed no statistically better success (94% vs 81%). TIP is a valid procedure for repair of penoscrotal hypospadias with chordee<30 degrees. The overall success (86%) is satisfactory. Surgeon's experience is the pillar for better success.

DISORDER OF SEX DEVELOPMENT: DESCRIPTION OF 2 CASES OF MALE PSEUDOHERMAPHRODITISM

Introduction. "Genetic errors" with malformations and hormonal alterations result in a broad spectrum of disorders of sexual identity difficult to classify for etiopathogenesis and anatomy. Male pseudohermaphroditism (PEM) is the result of defects in masculinisation, persistence of mullerian ducts or genital malformations. In these patients, there is always a 46 XY karyotype, male gonads with the external genitalia and phenotype completely or partially female. The authors describe 2 cases of PEM. Patients and Methods. RS and HNA, 9 and 15 years old. Both had 46 XY karyotype and female phenotype with the presence of penile clitoris and small vagina. The urethral meatus was positioned at the base of the penile clitoris and upper vagina and testicles, were located at the proximal portion of the inguinal canal.Patients were subjected to MRI showing absence of uterus and ovaries. The endoscopy described a small vagina dead-end about 4-5 cm long. Complete resection of the vagina, bilateral orchiopexy, correction of perineal hypospadias with urethral tubulization, reconstruction of the scrotum, with the results of penoscrotal hypospadias were performed. Discussion. Sexual differentiation is the process between VII and XII weeks of gestational age leading to formation of male or female fetus from embryo potentially bisexual. Brain Code gender is bipolar: male or female. In the sexual disorders there is a discrepancy between anatomical sex and the brain code. Genital malformation with a direct mechanism (external genitalia) and indirect (prenatal pathological imprinting on all the receptors of target organs) may exacerbate the brain deterioration of the code resulting in disease patterns difficult to manage according psychological and surgical aspects. Conclusions. Pediatric Surgeon plays a key role in the treatment of genital anomalies. Valutation of pelvic-perineal anatomy is important for the choice of sexual phenotype and related surgical strategy. Early correction of genital abnormality may effectively prevent the child present psychological, behavioral onsequences and problems in family and society.

CORRECTION OF BLADDER EXSTROPHY IN ADOLESCENT: 2 CASE REPORT

Introduction: bladder exstrophy is characterized by an incomplete development of anterior portion of bladder, urethra, abdominal wall and a median separation of pubic symphysis. We describe 2 clinical cases in adolescent treated with different surgical approach. Materials and Methods: two patients, one male and one female, respectively, 10 and 14 years old. Both cases had relapse: the bladder plate was performed in female when she was 2 years and in male when he was 6 years old. The male showed bladder exstrophy with epispadias; the female showed bifido clitoris, absence of minora labia with a small vaginal orifice. In both patients ano-rectal manometric and barium enema had normal parameters. The x-Ray basin showed diastasis of pubic bones, respectively, 7.5 cm in male and 10 cm in female. The male had closure of bladder and abdominal wall with transformation of epispadias to peno-scrotal hypospadias. The female had rectal reservoir (about 250cc), with amputation of the rectum with Hartmann&rsquo;s method and recanalization with Duhamel&rsquo;s method, anastomosis uretero rectal and vaginoplasty. Results: clinical and laboratory follow-up to date is 6 months. The female holds the urine about 2-3 hours during the day; in the night losses are not reported; the male shows dehiscence of abdominal and vesical wall with suprapubic fistula and loss of urine. The urethral peno-scrotal meatus appears patent. Conclusions: our experience, although limited in the number of cases and in the time of observation, is in agreement with the literature: we can say that the correction of bladder exstrophy in adolescents might be a urinary diversion with creation of rectal reservoir, useful for age of the patients and postoperative management. It is always necessary an adequate follow-up to check any complications.

Dyshormonogenetic goiter and associated non-thyroidal anomalies

Background: Dyshormonogenetic goiter (DG) refers to familial goitres owing to an inherited defect in the metabolism of thyroid hormones and accounts for 10-15% of all cases of congenital hypothyroidism. Aim and Objective: To identify dysmorphic features, cardiac and urogenital anomalies in patients with DG following in the pediatric endocrinology clinic. Materials and Methods: Eight adolescents following the pediatric endocrinology clinic for hypothyroidism and associated stigmata were identified with dyshormonogenesis using 99mTc radionuclide thyroid scintigraphy and confirmation by the Perchlorate discharge test during a 6-month period from January to July 2012. Screening for associated malformations was done using clinical examination, echocardiography and ultrasonography of abdomen. Results: The eight patients (two boys and six girls) had a mean age of 9.87 years. The mean duration of goitre was 36.12 months. Two patients had mental retardation and delayed developmental milestones one of whom had ectopic left kidney on renal scintigraphy. Mitral regurgitation was seen in one patient whereas renal anomalies in the form of ectopic kidney and small/contracted kidney with grade III hydronephrosis was seen in two patients. Penoscrotal hypospadias was identified in one of the patients who also had small/contracted kidney with grade III hydronephrosis and underwent pyeloplasty for the same. Dysmorphic features in the form of high arched palate, depressed nasal bridge and low set ears was seen in one patient. Conclusion: DG is associated with other extra-thyroidal congenital anomaly, some of which may need to be treated.

Prenatal Diagnosis of Penoscrotal Hypospadia in Third Trimester by Two- and Three-Dimensional Ultrasonography: A Case Report

Hypospadia is an abnormal development of the corpus spongiosum, that involves cavernosa urethra, as a result of an inadequate fusion of the urethral folds. The incidence ranges from 0.2 to 4.1 per 1,000 live births. Among the markers of hypospadia, isolated ventral or lateral curvature of the penis associated with shortening are the most important markers and, in severe cases, can result in the classic “tulip sign.” The diagnosis of hypospadia is uncommon unless there is a routine of detailed analysis of fetal genitalia morphology. The prenatal diagnosis is of great importance for genetic counseling and allows better planning of postnatal treatment. The three-dimensional ultrasonography (3DUS) in rendering mode enables better comprehension of the pathology by parents, facilitating postnatal planning. We report a case of penoscrotal hypospadia diagnosed at 33 weeks of gestation, suspected due to the absence of testicles in the scrotum and difficulty of penis visualization. We emphasize the findings of 3DUS and its importance in the pathology compression by parents.

Préparation à l’érythropoïétine avant chirurgie de l’hypospade : de meilleurs résultats ?

To study the effect of a preparation by erythropoietin before Onlay's intervention on postoperative hematocrits and medium-term results of the surgery. Twenty-one patients were operated on by Onlay's technique between 2001 January and 2008 September, after being treated by erythropoietin. Seven had a midshaft hypospadias, two a posterior hypospadias and 12 a penoscrotal hypospadias. All children were examinated four months after surgery to evaluate the surgical results. After the surgery, 18 children had an apical meatus (85.7%). Three had a balanopreputial meatus, two a stenosis of the meatus. Two children were reoperated on, one with the Duplay's technique, the other for a meatostomy. No fistula, no necrosis of the preputial flap was observed. The preoperative hematocrit was measured at 41%, with an increase of 3.8% because of the preparation. Peroperative blood loss was evaluated at 6.6%. After surgery, 12 children had an hematocrit inferior than 35%, four an hematocrit inferior than 30%. No transfusion was needed. Preparation by erythropoietin before severe hypospadias surgery seemed to have several advantages: a more elevated hematocrit after surgery than with an iron preparation alone, and a lower rate of postoperative complications, including fistulas and necrosis of the preputial flap.

Prenatal two‐ and three‐dimensional imaging in two cases of severe penoscrotal hypospadias

We present the prenatal two- and three-dimensional (3D) ultrasound (US) findings in two cases of severe penoscrotal hypospadias. 3D sonography was used for better definition of ambiguous genitalia. The images were compared with postnatal clinical features. Despite hypospadias being the most common urogenital anomaly of male neonates, the diagnosis is often missed before birth. Performing prenatal ultrasound should include the study of genitals, not only determining the sex.

250 MAMLD1 IS NOT ONLY INVOLVED IN TESTOSTERONE PRODUCTION IN FETAL TESTIS BUT ALSO MAY BE RELEVANT TO ADULT TESTICULAR FUNCTION

INTRODUCTION AND OBJECTIVES: MAMLD1 (Mastermindlike domain containing 1) has been shown to be a causative gene for hypospadias. We have shown that transient knockdown of Mamld1 results in reduced testosterone production in mouse Leydig tumor cells (MLTC-1). However the mechanism underlying the regulation of the genes encoding steroidogenic enzymes remains unclear. We reported the subsequent clinical features of MAMLD1 mutation positive patients and further studied Mamld1 knockdown assay to elucidate this mechanism. METHODS: Three hypospadias patients who have MAMLD1 mutation were included in this study. We measured pituitary-gonadal serum hormone values and underwent ultrasonography. We performed transient knockdown assay with siRNAs for Mamld1 using MLTC-1, and measured amounts of steroid hormones, mRNA expressions of steroidogenic enzymes and cell proliferation rate. RESULTS: We identified nonsense mutations (E124X and R653X) which undergo nonsense mediated mRNA decay in these 3 patients with penoscrotal hypospadias. The patients who have E124X mutations are half-siblings. In clinical findings of 3 patients who have MAMLD1 mutation, whereas hormone values remained within the normal range at previous report, testosterone was low response to hCG stimulation and LH/FSH were elevated at the age of 7 and 9. Moreover testicular microlithiasis was detected by ultrasonography in 2 cases. By Mamld1 knockdown in MLTC-1, 17-hydroxypregnenolone, 17-hydroxyprogesterone and downstream metabolite products were reduced and the expressions of Cyp17a1 mRNA were significantly decreased. Although effect of Mamld1 knockdown by siRNA continued until 72hrs, number of viable cells did not change compared to control. CONCLUSIONS: We concluded that knockdown of Mamld1 reduce production of steroid hormones via regulation of steroidogenic enzymes gene expressions, particularly Cyp17a1. MAMLD1/Mamld1 is not only involved in testosterone production in fetal testis but also may be associated with adult testicular function.

546 AN ALTERNATIVE FOR VENTRAL LENGTHENING IN CHILDREN WITH SEVERE PENILE CURVATURE THAT ALLOWS GRAFT COVERAGE DURING STAGED HYPOSPADIAS REPAIR

You have accessJournal of UrologyPediatrics: Congenital Anomalies - Lower Urinary Tract & Genitalia1 Apr 2011546 AN ALTERNATIVE FOR VENTRAL LENGTHENING IN CHILDREN WITH SEVERE PENILE CURVATURE THAT ALLOWS GRAFT COVERAGE DURING STAGED HYPOSPADIAS REPAIR Bruno Leslie, Bryce Weber, Rodrigo Romao, Walid Farhat, Darius Bagli, Armando Lorenzo, and Joao Pippi Salle Bruno LeslieBruno Leslie toronto, Canada More articles by this author , Bryce WeberBryce Weber toronto, Canada More articles by this author , Rodrigo RomaoRodrigo Romao toronto, Canada More articles by this author , Walid FarhatWalid Farhat toronto, Canada More articles by this author , Darius BagliDarius Bagli toronto, Canada More articles by this author , Armando LorenzoArmando Lorenzo toronto, Canada More articles by this author , and Joao Pippi SalleJoao Pippi Salle toronto, Canada More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1271AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Staged repair using preputial grafts has become a popular option for proximal hypospadias with severe curvature. Corporal ventral lengthening (CVL) with autologous, xenogenic or synthetic grafts are often employed, however the initial lack of vascular supply precludes simultaneous superposition of free grafts during first stage urethroplasty. Herein we report preliminary results of a surgical strategy aiming to overcome this limitation, allowing concurrent CVL and preputial grafting for urethroplasty. METHODS The medical records of patients who underwent staged preputial graft urethroplasty (SPGU) for primary repair of perineal or penoscrotal hypospadias with severe curvature were retrospectively reviewed. All patients received pre operative testosterone. The decision to divide the urethral plate was made after complete degloving and urethral mobilization. Multiple deep ventral transverse incisions of the tunica albuginea from 3 to 9 o'clock position were performed in patients with persistent intrinsic curvature after plate transection. An inner preputial graft was then harvested and quilted directly over the incised albuginea, and a tie-over dressing applied. Second stage was done approximately 6 months later, when the graft was tubularized and covered with tunica vaginalis or dartos flap. Prior to tubularization an erection test was repeated and residual curvature addressed with dorsal plication (DP), if necessary. Age, outcomes, need for DP and complications were recorded. RESULTS 30 patients completed the two stages from 2006 to 2010. Mean age at first stage was 18 months (range 10m–11y) and mean interval between stages was 8 months (range 6–11). Mean follow up after the second stage was 16 months (range 6–36). All grafts took well and were suitable for tubularization. DP was required for minor residual ventral curvature in 14/30 (47%) patients. Relevant complications included a long urethral stricture secondary to balanitis xerotica obliterans (1), ventral skin contracture (1), small urethrocutaneous fistulas (2), glans dehiscence (2) and recurrence of mild curvature (2). The remaining 22 cases have no ventral curvature and early excellent cosmetic results, with a slitlike meatus placed in the glans. CONCLUSIONS Our results suggest that the use of deep ventral transverse corporeal incisions for correction of severe curvature allows SPGU and concurrent CVL. The early cosmetic and functional results with this approach are satisfactory with an acceptable complication rate. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e221-e222 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Bruno Leslie toronto, Canada More articles by this author Bryce Weber toronto, Canada More articles by this author Rodrigo Romao toronto, Canada More articles by this author Walid Farhat toronto, Canada More articles by this author Darius Bagli toronto, Canada More articles by this author Armando Lorenzo toronto, Canada More articles by this author Joao Pippi Salle toronto, Canada More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Congenital pouch colon and segmental dilatation of the colon: A report of two unusual cases

This report describes two unusual cases of anorectal malformation. The first had a type III congenital pouch colon with a colovesical fistula. In the other very similar case, segmental dilatation of the colon was present along with penoscrotal hypospadias and, distally, a length of normal colon ending in a rectourethral fistula. In both patients, the appendix was short, stubby and a Y-shaped duplication of the normal colon was present just proximal to the dilated segment of colon.

Mixed gonadal dysgenesis: whole life follow-up of a rare case

There are two forms of gonadal dysgenesis - mixed and pure. In the mixed form, some differentiated gonads as well as some either ovarian or testicular rudiments are present. This form results in a number of phenotypes with a possibility of malignant transformation. In the pure form occurring in female gender, also some rudimental gonads are bilaterally present. In the case of simultaneous presence of Y chromosome, also some malignant transformation may appear (Siklar et al. 2007). Chromosomal aberrations are present in 2-7 % adult pairs with fertility disorders and in 0.6 % of newborns. However, only few cases with similar chromosomal aberrations were described so far (Roubin et al. 1977; Alexander et al. 1978; Teyssier et al. 1982; Caglayan et al. 2009). Mixed gonadal dysgenesis presents as a unilateral testis, usually intraabdominal, also with a streak gonad on contralateral side, and persistent mullerian structures. 45X/45XY karyotype is the most frequent in such cases with predominance of 45X cells in both peripheral lymphocytes and gonads. We present a rare case of a left undescended testis, normally descended right testis, with penoscrotal hypospadias, who had a normal karyotype and whose histopathological findings were endometrial tissue and fallopian tube in left testicular biopsy. Gonadal dysgenesis should always be kept in mind because of a possibility of undescended testis and proximal hypospadias. If karyotype reveals a 46XY gonadal dysgenesis, these patients need the careful follow-up to screen for gonadoblastoma in remaining normal testis. Subjecting the patients to prophylactic orchidectomy with hormone replacement can be an additional option in such patients.

Tubularized Incised Plate (Tip) Repair for Penoscrotal Hypospadias: Critical Analysis of Results

Purpose This is a retrospective analysis of factors affecting outcome of TIP repair for penoscrotal Hypospadias. Material and Methods Data of all patients who underwent TIP repair for penoscrotal Hypospadias by a single surgeon (A.T.H) were retrieved. Significant chordee (> 30 degree) was a contraindication for TIP. Chordee was corrected after extended bulbar dissection of the urethra with dorsal midline tunica albuginea placation. The neourethra was sutured with 7/0 or 6/0 continuous subepithelial polyglycate suture. All repairs were stented for 7-10 days. Follow-up was carried out 3-monthly in the first year and annually thereafter. Repairs were divided into 2 groups; group 1 included those performed in the first 2 years after fellowship training, and group 2 included repairs performed afterwards. Success was defined as orthotopic meatus with forward adequate stream with no stenosis, fistula or diverticulum. Chi-sqaure test was used for univariate analysis and binary logistic regression was used for multivariate analysis. Statistical significance was defined as p value Results Data for 90 patients were retrieved (from July 2001 to March 2009). Most patients (77%) were older than 2 years at surgery. Group 1 patients were 20 and group 2 were 70. The neourethra was covered with spongioplasty in 25 and dartos flap in 65. The overall success was 86% (65% fro group 1 and 91% for group 2). On both univariate and multivariate analysis, more experience and coverage with dartos flap were associated with statistically better outcome. Age at surgery had no statistical impact on outcome. Conclusions TIP is a valid procedure for repair of penoscrotal Hypospadias with mild chordee . The overall outcome (86%) is satisfactory. Coverage of the neourethra with a dartos flap and experience are the pillars of statistically significant better success.

Isolated micropenis reveals partial androgen insensitivity syndrome confirmed by molecular analysis

Partial androgen insensitivity syndrome (PAIS) is the milder variant of androgen receptor (AR) defects. The subtle effects of AR mutations present in a patient with micropenis, peno-scrotal hypospadias, infertility, clitoromegaly and posterior labial fusion. We studied the association of isolated micropenis with the genetic defects resulting in androgen resistance, that is, AR gene defects and 5-alpha reductase type 2 (SRD5A2) deficiency. We describe two cases of isolated micropenis: one in a 14-year-old boy and the other in a 3-year-old boy who was followed until he was 10 years old. There were no findings of hypospadias, cryptorchidism or gynecomastia in either of these patients. Serum gonadotrophin and androgen levels were obtained and karyotyping was done. Human chorionic gonadotropin (hCG) stimulation testing assessed the functional capacity of the testes. DNA was extracted from peripheral leukocytes, and all exons of the SRD5A2 and AR genes were amplified by polymerase chain reaction and sequenced. In both patients, baseline testosterone (T) level was low and the values were elevated after hCG testing. The sequence of the SRD5A2 gene was normal in patient 1, and a heterozygous polymorphism, V89L, was found in patient 2. Two known mutations, P390S and A870V, were identified in patients 1 and 2, respectively. Mutations in the AR gene can be associated with isolated micropenis without other features of PAIS, such as hypospadias or gynecomastia. This underlines the importance of including AR gene analysis in the evaluation of isolated micropenis with normal plasma T to ensure proper management of the patient and appropriate genetic counseling for the family.

46,XY and 45,X/46,XY testicular dysgenesis: similar gonadal and genital phenotype, different prognosis

The objective of this study was to describe the change in diagnosis and prognosis of a child with testicular dysgenesis and 46,XY karyotype after detection of a 45,X cell line and to discuss the difficulties caused by the terms mixed gonadal dysgenesis (MGD) and XY partial gonadal dysgenesis (XYPGD). One case was reported including clinical and laboratory findings of a child of 41-day-old infant with 1.3-cm phallus, penoscrotal hypospadias and left prepubertal testis. Karyotype 46,XY (16 cells), normal hormone levels. Right streak gonad, epididymis and müllerian remnants were removed; initial diagnosis was XYPGD. Persistent growth retardation led to further cytogenetic analysis (50 cells) and detection of a 45,X cell line. Detection of a 45,X lineage changed both the diagnosis to MGD and also the prognosis.The number of cells analyzed in karyotyping is critical. Use of MGD and XYPGD to designate both a histological picture and a syndromic diagnosis, results in lack of emphasis on clinical differences between 46,XY and 45,X/46,XY subjects.

Mixed gonadal dysgenesis with normal karyotype : A rare case report

Mixed gonadal dysgenesis (MGD) presents as a unilateral testis, usually intraabdominal, a streak gonad on contralateral side, and persistent mullerian structures. 45X/45XY karyotype is most frequent in such cases with predominance of 45X cells in both peripheral lymphocytes and gonads. We present a rare case of a left undescended testis, normally descended right testis, with penoscrotal hypospadias, who had a normal karyotype and whose histopathological findings were endometrial tissue and fallopian tube in left testicular biopsy. Gonadal dysgenesis should always be kept a possibility in patient with undescended testis and proximal hypospadias. If karyotype reveals a 46XY gonadal dysgenesis, these patients need all the more careful follow-up to screen for gonadoblastoma in remaining normal testis. Subjecting the patients to prophylactic orchidectomy with hormone replacement can be an additional option in such patients.

DISORDER OF SEX DEVELOPMENT: DESCRIPTION OF 2 CASES OF MALE PSEUDOHERMAPHRODITISM

Introduction. Genetic errors with malformations and hormonal alterations result in a broad spectrum of disorders of sexual identity difficult to classify for etiopathogenesis and anatomy. Male pseudohermaphroditism (PEM) is the result of defects in masculinisation, persistence of mullerian ducts or genital malformations. In these patients, there is always a 46 XY karyotype, male gonads with the external genitalia and phenotype completely or partially female. The authors describe 2 cases of PEM. Patients and Methods. RS and HNA, 9 and 15 years old. Both had 46 XY karyotype and female phenotype with the presence of penile clitoris and small vagina. The urethral meatus was positioned at the base of the penile clitoris and upper vagina and testicles, were located at the proximal portion of the inguinal canal.Patients were subjected to MRI showing absence of uterus and ovaries. The endoscopy described a small vagina dead-end about 4-5 cm long. Complete resection of the vagina, bilateral orchiopexy, correction of perineal hypospadias with urethral tubulization, reconstruction of the scrotum, with the results of penoscrotal hypospadias were performed. Discussion. Sexual differentiation is the process between VII and XII weeks of gestational age leading to formation of male or female fetus from embryo potentially bisexual. Brain Code gender is bipolar: male or female. In the sexual disorders there is a discrepancy between anatomical sex and the brain code. Genital malformation with a direct mechanism (external genitalia) and indirect (prenatal pathological imprinting on all the receptors of target organs) may exacerbate the brain deterioration of the code resulting in disease patterns difficult to manage according psychological and surgical aspects. Conclusions. Pediatric Surgeon plays a key role in the treatment of genital anomalies. Valutation of pelvic-perineal anatomy is important for the choice of sexual phenotype and related surgical strategy. Early correction of genital abnormality may effectively prevent the child present psychological, behavioral onsequences and problems in family and society.

DISORDER OF SEX DEVELOPMENT: DESCRIPTION OF 2 CASES OF MALE PSEUDOHERMAPHRODITISM

Introduction. "Genetic errors" with malformations and hormonal alterations result in a broad spectrum of disorders of sexual identity difficult to classify for etiopathogenesis and anatomy. Male pseudohermaphroditism (PEM) is the result of defects in masculinisation, persistence of mullerian ducts or genital malformations. In these patients, there is always a 46 XY karyotype, male gonads with the external genitalia and phenotype completely or partially female. The authors describe 2 cases of PEM. Patients and Methods. RS and HNA, 9 and 15 years old. Both had 46 XY karyotype and female phenotype with the presence of penile clitoris and small vagina. The urethral meatus was positioned at the base of the penile clitoris and upper vagina and testicles, were located at the proximal portion of the inguinal canal.Patients were subjected to MRI showing absence of uterus and ovaries. The endoscopy described a small vagina dead-end about 4-5 cm long. Complete resection of the vagina, bilateral orchiopexy, correction of perineal hypospadias with urethral tubulization, reconstruction of the scrotum, with the results of penoscrotal hypospadias were performed. Discussion. Sexual differentiation is the process between VII and XII weeks of gestational age leading to formation of male or female fetus from embryo potentially bisexual. Brain Code gender is bipolar: male or female. In the sexual disorders there is a discrepancy between anatomical sex and the brain code. Genital malformation with a direct mechanism (external genitalia) and indirect (prenatal pathological imprinting on all the receptors of target organs) may exacerbate the brain deterioration of the code resulting in disease patterns difficult to manage according psychological and surgical aspects. Conclusions. Pediatric Surgeon plays a key role in the treatment of genital anomalies. Valutation of pelvic-perineal anatomy is important for the choice of sexual phenotype and related surgical strategy. Early correction of genital abnormality may effectively prevent the child present psychological, behavioral onsequences and problems in family and society.

Clinical Dilemmas and Surgical Treatment of Penoscrotal, Scrotal and Perineal Hypospadias

Hypospadia is the most common congenital malformation of the urinary tract. It is a malformation with the opening of the urethra proximally from the usual site. The meatal opening can be anywhere alone the shaft of the penis, or in more severe forms, within the scrotum, or in the perineum. Consequently the hypospadias can be distal, medial and proximal. The proximal ones can be penoscrotal (PS), scrotal (SC) and perineal (PE). The cause of hypospadias is largely unknown; however, current epidemiology and laboratory studies have shed new light into the etiology of hypospadias. With recent advancements in molecular biology, microarray technology, it appears that hypospadias is potentially related to disrupted gene expression. Currently, the only available treatment is surgery. The aim of this study was to present our results of the surgical correction of hypospadias and methods used to answer the clinical dilemmas about the gender. Authors have used two methods for a surgical resolution of the hypospadia - one-step operation suggested by Snodgrass and two-step operation, employing free graft suggested by Bracka. Clinical dilemmas regarding the gender were answered using cytogenetic assessment through lymphocyte cultivation method, suggested by Seabright. The cytogenetic assessment was carried in 23 patients with proximal hypospadia (penoscrotal, scrotal and perineal). Characteristic male cariotype (46, XY) was found in 22 patients. In one patient, with scrotal hypospadia, we found the characteristic female cariotype. This patient had testicles. The patient with female cariotype had a TDG gene that determines the differentiation of the testicles. Although surgery remains the only therapy for the treatment of the hypospadias, better understanding of the molecular and hormonal mechanisms behind the diseases may contribute to the prevention and the decrease in the incidence of the malformation. Cytogenetic testing in patients with unclear gender is important in planning further treatment.

The spectrum of phenotypes associated with mutations in steroidogenic factor 1 (SF-1, NR5A1, Ad4BP) includes severe penoscrotal hypospadias in 46,XY males without adrenal insufficiency.

ObjectiveHypospadias is a frequent congenital anomaly but in most cases an underlying cause is not found. Steroidogenic factor 1 (SF-1, NR5A1, Ad4BP) is a key regulator of human sex development and an increasing number of SF-1 (NR5A1) mutations are reported in 46,XY disorders of sex development (DSD). We hypothesized that NR5A1 mutations could be identified in boys with hypospadias.Design and methodsMutational analysis of NR5A1 in 60 individuals with varying degrees of hypospadias from the German DSD network.ResultsHeterozygous NR5A1 mutations were found in three out of 60 cases. These three individuals represented the most severe end of the spectrum studied as they presented with penoscrotal hypospadias, variable androgenization of the phallus and undescended testes (three out of 20 cases (15%) with this phenotype). Testosterone was low in all three patients and inhibin B/anti-Müllerian hormone (AMH) were low in two patients. Two patients had a clear male gender assignment. Gender re-assignment to male occurred in the third case. Two patients harbored heterozygous nonsense mutations (p.Q107X/WT, p.E11X/WT). One patient had a heterozygous splice site mutation in intron 2 (c.103-3A/WT) predicted to disrupt the main DNA-binding motif. Functional studies of the nonsense mutants showed impaired transcriptional activation of an SF-1-responsive promoter (Cyp11a). To date, adrenal insufficiency has not occurred in any of the patients.ConclusionsSF-1 (NR5A1) mutations should be considered in 46,XY individuals with severe (penoscrotal) hypospadias, especially if undescended testes, low testosterone, or low inhibin B/AMH levels are present. SF-1 mutations in milder forms of idiopathic hypospadias are unlikely to be common.