Hypospadias Research Articles

Trisomy 26 in a Holstein calf with disorders of sex development.

Hypospadias occurs sporadically in male livestock and is characterized by a non-fused urethra during fetal development. In this study, perineal hypospadias, a bifid scrotum, penile hypoplasia, and bilateral abdominal cryptorchidism were diagnosed in a neonatal Holstein male calf. Septicemia was also suspected due to hypothermia, blurred conjunctivae, and loss of sucking and swallowing reflexes. Gross pathology revealed that both testicles were located intraabdominally caudally to the kidneys. Histopathological examination of the hypospadias showed a urothelium-lined mucosal fold and parts of the corpus cavernosum penis and prepuce in the subcutis. Whole genome sequencing was performed on the affected calf. Analysis of short-read coverage depth along the chromosomes identified an entire extra copy of chromosome 26. Based on the comparison of available variant calling data from the sire, the identified trisomy 26 is due to non-disjunction of homologous chromosomes during the generation of paternal gametes. We have shown for the first time an association between bovine hypospadias and trisomy 26, which adds to the understanding of variation in fetal male sexual development.

Assessment of the CDC hypospadias atlas for epidemiological research - A survey of experts

Hypospadias is a common congenital malformation. There are several classification systems for hypospadias. However, the phenotypic subtypes of hypospadias are inconsistently reported across databases due to the inherently subtle variability of the penile anatomy. Consistent classification of hypospadias would enable more accurate data regarding etiological correlates of specific subtypes as well as perioperative care and surgical outcomes. Existing classifications are designed for use by hypospadias surgeons, although there is a need for a system for epidemiologic data abstractors, who are generally not clinicians. The online Center for Disease Control (CDC) manual for birth defect surveillance includes a hypospadias atlas with photograph representation for different hypospadias phenotypic subtypes. However, this atlas is not widely known or used as a reference by pediatric urologists. We sought to evaluate the consistency amongst surgeons who specialize in managing this condition on the classification of hypospadias using the CDC atlas to determine whether this can be a tool in epidemiologic data collection. We developed a questionnaire using photographs taken directly from the CDC atlas for hypospadias. Demographic data regarding geographical location and years in practice also were obtained. The survey was distributed via email to members of the Society for Pediatric Urology and American Association of Pediatric Urologists. Responses were anonymously collected. 166 responses were received from 407 surveys request yielding a response rate of 40.8%. Agreement with the CDC atlas on the classification of hypospadias by responders was 93.4% for glanular hypospadias, 56.6% for subcoronal hypospadias, 3.6% for penile hypospadias, 54.2 for scrotal hypospadias, and 59% for perineal hypospadias. Our survey indicated that there is general disagreement in classification of hypospadias in the CDC atlas amongst members of pediatric urology societies. There exists a need for better standardization of a hypospadias classification system for epidemiologic research in hypospadias. Limitations of our study include a less than 50% of survey responses received and large proportion of responders were from the United States.

Rectal duplication in association of other developmental malformations

Purpose of the study. It is to show the difficulty of making a diagnosis and choosing surgical treatment as a rare disease - duplication of the rectum in combination with other anomalies of the development of organs and systems.Material and research methods. Under our supervision there were 2 children diagnosed with congenital anomaly of the gastrointestinal tract. Isolated duplication of the rectum. Perineal hypospadias. Narrowing of the vesicoureteral segment on the right. Ureterohydronephrosis Ⅰ degree on the right.Results. A control study did not reveal any pathology in the internal organs of the children. Ultrasound of the urinary system: the pyelocaliceal system is not dilated, no symptoms of megaureter were detected. Children do not lag behind their peers in mental and physical development. Today, the children’s condition is satisfactory, there are no complaints, they are under the supervision of a pediatric surgeon.Conclusion. Duplication of the rectum is an isolated rare pathology in children in combination with malformations of the genitourinary system, with very diverse clinical manifestations, which poses a problem in making a diagnosis before surgery. Open surgery is safer and good results can be achieved.

The effect of preoperative hormonal stimulation on the urethral plate; A histologic and histochemical study

Preoperative hormone stimulation (PHS) is used to increase the glans size and may improve the cosmetic appearance after hypospadias surgery. The exact effect of PHS on different penile tissues remains unclear and controversial. Previous studies showed that PHS increased vessel density in the foreskin. However, the effect of PHS on the urethral has never been studied before. In this study we examine the PHS effects on the urethral plate. Specimens of the urethral plate and the underlying tissue were excised to correct severe chordee in 16 children with proximal and perineal hypospadias with severe chordee in 2 groups. Group A consisted of 8 children received PHS prior to surgery. Group B included 8 children with proximal and perineal hypospadias with severe chordee who did not receive PHS and served as a control group. Specimens were examined blindly using hematoxylin-eosin and elastic van-Gieson stain as well as factor 8 and SMA antibodies. The median age of Group A was 13 (range 10-20) months. The median age of Group B (without prior PHS) was 17 (range 14-29) months (p=0,03). The median vessel-density in group A (82 vessels per mm2) was significantly higher than in Group B (65 per mm2), (p<0.05). The median vessel diameter was also significantly higher in Group A (13μm) than in Group B (11μm), (p<0.05). The median epithelial layer thickness in Group A was 110μm and in Group B 98μm, but showed no statistical significance (p=0,16). There was no significant change in dartos fascia layer thickness or androgen receptor expression. There was no visual change in the organization of elastic fibers. This study is the first study to document the effect of PHS on the urethral plate in hypospadias with severe chordee. PHS significantly increased the median vessel-density as well as median vessel diameter as compared to a matching control group. The findings of the study may justify PHS administration before the first operation to improve the vascularity and may reduce the severity of chordee.

Understanding the Endocrine and Molecular Signaling Cascade Regulation Pathways in Children with Hypospadias.

Hypospadias (HS) is a congenital defect that occurs due to defective androgenization. It is characterized by the aberrant location of the urinary meatus on the ventral aspect of the penis with various degrees of severity. The molecular mechanisms and genetic associations underlying the condition remain largely unknown. Existing literature revolves around surgical and medical management of the condition. Human chorionic gonadotropin pretreatment in HS is proposed to decrease the severity of the anomaly and improve the clinical outcome of surgery. The underlying mechanisms that drive these outcomes have not been explored. Few studies have explored the endocrine signaling and pathways which lead to the development of the condition. Hence, a prospective study was conducted to understand the same. Eighteen children with mid or proximal penile HS were included as cases, and nine children undergoing circumcision for phimosis (nonpathological) were included as controls. Serum samples from all these children and preputial skin samples taken during surgery were used in the analysis. The hormonal milieu was normal in all children in our cohort. A comparison of previously reported genes with our cohort sequencing revealed changes in several major pathways involved in cell proliferation and differentiation, cell signaling, angiogenesis, and immune response pathways. Compared with healthy controls, HS subjects had 152 differentially expressed genes. Of these, 93 genes were up-regulated, and 59 genes were found to be significantly down-regulated. The gene expression evaluation also showed changes in expression patterns in inflammatory genes and link RNAs, unlike previously reported genes.

Surgical treatment of perineal hypospadias with complete penoscrotal transposition in DSD patients: Our experience with a “three-staged” reconstructive procedure

Surgical treatment of perineal hypospadias with complete penoscrotal transposition in DSD patients: Our experience with a “three-staged” reconstructive procedure

Intracavernosal pressure of the erect penis in children with hypospadias.

This study objective is to examine the intracavernosal pressure (ICP) in hypospadias boys with and without previous corporotomies. Retrospectively, the ICPs that were measured routinely as part of the artificial erection test in boys who underwent hypospadias repair were collected. The measurement (mmHg) included a slow manual saline instillation and a 21-gauge needle in the corpora cavernosa, which was connected to a pressure monitor. The full and rigid erections were defined according to the Erection Hardness Score by agreement between the two surgeons operating on the patient. Included were 61 boys with a median age of 15 months (IQR 8-27). Group A included 32 boys with coronal, subcoronal, or penile hypospadias. Group B included 29 boys with penoscrotal, scrotal, and perineal hypospadias. The median pressures at full erection for Groups A and B were 71.5 (IQR 59-79) and 62.5 (IQR 48-71) (p = 0.036), respectively, and at rigid erection were 283 (IQR 219-310) and 237 (IQR 182-278) (p = 0.032), respectively. In group B, median pressures at full erection for boys with and without previous corporotomies were 53.5 (IQR 45-65) and 69 (IQR 57-82), respectively (p = 0.001), and at rigid erection were 189.5 (IQR 113-263) and 264.5 (IQR 226-298), respectively (p = 0.003). In a comparison between group A boys to 18 boys in group B who did not have corporotomies, the median pressures at full erection were 71.5 (IQR 59-79) and 69 (IQR 57-82), respectively (p = 0.9), and at rigid erection were 283 (IQR 219-310) and 264 (IQR 226-298), respectively (p = 0.86). In conclusion, ICPs of artificial erections are lower in proximal hypospadias and in boys with previous corporotomies. The durability and the implications of these pressures require further research.

Insights into enlarged prostatic utricles and Müllerian duct system remnants associated with posterior hypospadias

The prostatic utricle (PU) consists of the caudal remnant of the Müllerian duct and the urogenital sinus. The term "vagina masculina" is used if other Müllerian structures are associated with the PU. This work aims to investigate the incidence, management, and follow up of enlarged PUs and Müllerian remnants in males with posterior hypospadias. This study presents a retrospective review of cases presented with posterior hypospadias over a 5-year period. Prior to hypospadias repair, retrograde urethrograms were used to investigate enlarged PU. Subsequently, they were classified according to the Ikoma score and further assessed by karyotyping and cystoscope. Surgical excision was indicated in cases with symptomatic utricles or vagina masculina. Thirty patients were included in the study in the period between 2015 and 2020 (Table). All cases were asymptomatic initially. Twelve patients were diagnosed with enlarged PU; three of them had vagina masculina. One case with perineal hypospadias had a separate perineal opening for PU. Following hypospadias repair, three of the eight cases treated conservatively turned symptomatic. The incidence of enlarged PU and Müllerian remnants varied among different studies. However, it increased as the severity of hypospadias increased. Preoperative urethrogram was helpful in the diagnosis and classification of PU, but it had its limitations. Cystoscope was more advantageous in diagnosing vagina masculina. Although most cases were asymptomatic, some turned symptomatic after hypospadias repair. Some cases with perineal hypospadias had PU with a separate perineal opening. The incidence of enlarged PUs or Müllerian remnants was 40%. Although cases were asymptomatic before hypospadias surgery, some cases turned into symptomatic after hypospadias repair. In some cases, the PU or Müllerian remnants had a separate perineal opening. They can be classified as a particular form of Ikoma grade III necessitating surgical intervention.

Outpatient surgery for penile hypospadias in pediatric urology: A monocentric experience with a mean follow-up of 3years

Hypospadias is one of the most common congenital anomalies in men. Outpatient surgery has been proposed but is not widespread. The aim of this study was to evaluate our experience of outpatient surgery for penile hypospadias repair and to specify the constraints for a result similar to a conventional inpatient procedure. Observational, retrospective and single-center study, including all the patients operated on hypospadias for the first time by one of the 3senior surgeons, between January 2011 and March 2018. Peno-scrotal and perineal hypospadias were excluded because systematically hospitalized. One hundred sixty-six patients were included. 67patients (40,4%) were treated on an outpatient basis. The mean age at the time of procedure was 15.6 (6-51) months. Forms with curvature were almost exclusively hospitalized (1 vs. 25, P<0.001). There was no significant difference for anterior penile forms (60 vs. 81, P=0.06). Middle and posterior hypospadias were more often hospitalized, although outpatient experience exists. There were no more complications in the outpatient group. Outpatient hypospadias surgery seems to be achievable in most of the cases, provided that medical care is standardized and multidisciplinary, the staff is trained and involved and a specific organization is put in place in the department. Evaluation of the socio-family environment is therefore fundamental.

The Natural (non-invasive) Erection Test: Is it a reliable alternative to the artificial erection test?

To test the accuracy and reliability of the natural erection test (NET) as compared to the artificial erection test in assessing penile curvature in hypospadias. 50 children underwent both natural and artificial erection tests intraoperatively between January 2020 and October 2021. These included 5 glandular, 26 distal, 9 proximal, and 10 perineal hypospadias patients with curvature. The mean follow up period was 20 months (range 16-37). Under anesthesia, the curvature was assessed before degloving, then after degloving using both the natural and the artificial erection test. The NET test was repeated after curvature correction (3 times per patient). The measurements were analyzed using paired t-test. Two fingers of the left hand press just below the symphysis pubis to stop blood drainage from the penis and two fingers of the right hand massage the blood from the perineum distally into the penis until it becomes hard without tourniquet. The standard artificial erection test was performed using saline injected through a butterfly needle into the corporeal bodies without tourniquet. Photos were taken of both tests using the exact angle and angle of curvature was measured using Angle Meter App. There was no statistically significant difference between both erection tests with a P value of 0.705. The Bland-Altman plot also showed that all studied children have a difference in their natural and artificial erection tests within the limits of agreements. Erection is commonly induced using the artificial saline injected erection test first described by Gittes and less commonly using pharmaceutical erection test first described by Perovic. The severity of chordee apparent during artificial erection test varies with the amount of pressure used during injection. Also, it is difficult to place the tourniquet proximal enough to detect chordee at the base of the penis. It may be associated with hematoma formation, oedema, postoperative pain and the need for multiple punctures to assess the curvature before and after repair. Disadvantages of the pharmacological-induced erections in hypospadias include increased blood loss during erection, additional cost, and the need for a reversal agent. The natural erection test mimic the normal erection mechanism and may avoid all these potential disadvantages. The study showed that the natural erection test is easy to perform, non-invasive, non-traumatic and can be repeated several times intraoperatively without the need of repeated puncturing of the corpora cavernosa and avoids the potential risks and complications of the artificial erection test.

Preoperative hormone stimulation; does it increase hypospadias postoperative complications?

To assess the effect of Preoperative Hormone Stimulation (PHS) on glans size in proximal hypospadias with chordee and small glans, and to determine if PHS is associated with increased postoperative complications. Between 2014 and 2021, 101 cases of proximal hypospadias with small glans (12mm or less) were operated upon in our hospital and are the basis of this cohort. All patients underwent a standard two-stage surgical repair, undergoing a correction of the chordee in the first operation and urethroplasty in the second operation. All patients included were operated by the same surgeon. They were classified into two groups; Group A: 50 children were operated upon between 2014 and 2017 and did not receive PHS and Group B: 51 children operated between 2018 and 2021 and received PHS. Glans dimensions including Dorsal Longitudinal Length (DLL) and Glans Width (GW) were measured during the first operation. PHS was given 1-2 months before the second operation in Group B. The glans dimensions were measured again during the second operation after PHS. Follow up period ranged from 2 to 9 years (mean 5 years). Following PHS a statistically significant increase in glans length (p=0.042) and glans width (p=0.011) was observed at the second operation, with 36 patients (70%) showing a mean glans width increase of 2.78mm (range 2-8mm) after receiving PHS. There was no statistically significant difference in the complication rates between the two groups (p=0.556) with a fragility index of zero (FI=0). The present study separates itself from most other studies in the literature, in the fact that it has included only a specific group of proximal and perineal hypospadias with severe chordee and glans width of 12mm or less and that glans dimensions were always objectively and accurately measured under general anesthesia. The other major difference is that PHS in our study was given after and not before the first operation. Furthermore, the fact that all patients prior to 2018 did not receive PHS and all patients after 2018 received PHS, indicates that there was no selection bias. This study shows that PHS results in an increase the size of the glans in 70% of patients with hypospadias and a small glans without an increase in postoperative complications.

(277) Proposal for a Clearer Definition and Classification of Urethral Complications Following Transmasculine Gender Affirmation Surgery

Abstract Introduction The use of free flap microsurgical neophallus construction with integrated urethra have improved outcomes for transmasculine gender affirmation surgery (GAS) but there is no accepted gold standard. Many authors have described urethral complications but only in heterogenous and small cohorts. Anatomical nomenclature is also confusing. Objective We aim to describe urethral complications in the largest cohort of patients to date and propose a naming and classification system to improve reporting, research and management of this common problem. Methods All transmasculine individuals undergoing phalloplasty including a free flap urethroplasty, with staged urethral lengthening at our centre over five consecutive years (2014 – 2019) were retrospectively reviewed from a prospective database. Metoidioplasty was excluded. The incidence, timing and management of urethral complications were extracted from a prospective database. Statistical analysis was by Chi-squared test. Results Three hundred and seventeen individuals with median follow-up of 4.3 years (interquartile range 3.6– 5.0 years) were included. Types of phalloplasty include forearm flap, anterolateral thigh flap and abdominal flap with free flap urethroplasty. Almost half (43.5%) developed a urethral complication (fistula, stricture, severe post-micturition dribbling or urethral hair/stone); most commonly fistulae (48.5%) followed by strictures (37.4%). Complications were significantly higher in flaps with integrated urethra compared to staged combination free flap urethroplasty (39% compared to 10%, p&amp;lt;0.0003). Forty-four individuals (12.4%) developed more than one complication (31% of complications). Overall, complications were mostly in the phallus (flap-related) (72.2%) followed by scrotal and perineal urethra. Repairs before and during routine second stage urethral lengthening were for phallus complications comprising fistulas and strictures. Strictures were more common than fistulas in contrast to individuals before urethral lengthening (p&amp;lt;0.001). Staging the urethral lengthening allowed 81.6% of individuals to be asymptomatic while awaiting routine repair. Vaginectomy did not reduce the risk of urethral fistulae. Conclusions The largest series to date suggests that urethral complications continue to be common following phalloplasty and are mostly phallus or flap related. Complications may also be lower if a staged free flap urethroplasty is offered. We show that the nature of urethral complications in phalloplasty change depending on the stage of genital GAS and should be classified based on type, location and timing of occurrence. This classification standardises reporting and will help guide the approach for surgical correction. Complications in the phallus urethra relate to an issue with the free flap and requires a different approach compared to complications following urethral lengthening that are more likely in the scrotal or native urethra. Many complications occur prior to urethral lengthening (81.6%) and can be repaired routinely at that time. Furthermore, we propose that the urethral segments are called the phallus, scrotal and native urethra to allow for clear and concise nomenclature. Disclosure No

Repair of proximal hypospadias with single-stage (Duckett's method) or Bracka two-stage: a retrospective comparative cohort study.

Surgical correction of proximal hypospadias is challenging. The complication rate of proximal hypospadias is still high, and the debate over its optimal treatment is ongoing. Duckett's method is a classic non-staging operation, and two-stage Bracka repair is an attractive alternative procedure. Herein, we retrospectively analyzed the effects of two surgical techniques on proximal hypospadias in order to reduce the complication rates of proximal hypospadias, and analyzed the various risk factors that cause complications. This study retrospectively evaluated 94 consecutive patients who underwent repair of penoscrotal or proximal defects between 2015 and 2019. Patients were assigned to two groups: 46 patients were treated with Bracka and 48 with Duckett. Patient age at surgery, urethral meatus location, and postoperative complications were recorded. One-way analysis of variance (ANOVA) was used to analyze the length and curvature of the penis and the length of the urethral defect. There was no significant difference between the two groups in terms of age and type of hypospadias. In the Bracka group, there was 1 case (2.2%) of meatal stenosis after the first stage, which was restored with ureteral dilatation. After second-stage repair, a urethral fistula was noted in 4 cases (8.7%) and strictures in 2 cases (4.3%). In the Duckett group, urethral fistulas were noted in 8 cases (16.7%), strictures in 4 cases (8.3%), partial glans dehiscence in 4 cases (8.3%), and diverticulum in 1 case (2.1%) postoperatively. Compared with the Duckett group, the overall complication rate for Bracka repair was lower (35.4% vs. 13%, P=0.016). In addition, compared with the Duckett group, children with perineal hypospadias who were treated with the Bracka operation had fewer postoperative complications (100% vs. 13%, P=0.015). Risk factor analysis showed that the initial curvature of the penis, initial urethral defect, and degree of penile curvature after skin degloving were not correlated with complications. There was a significant correlation between urethral defects after correction of the chordee and urethral fistulas (P=0.019). Compared with the Duckett procedure, the Bracka two-stage repair may be a safer and more reliable approach for proximal hypospadias in children. The Bracka two-stage repair should be used for perineal hypospadias. The larger the urethral defect after chordee correction, the greater the possibility of a postoperative urethral fistula.

Hipospadia em dois gatos - relato de caso

ABSTRACT Hypospadias is an uncommon sexual development disorder in cats, in which the urethral opening is not in its anatomical location on the penis. The purpose of this report is to describe two cases of hypospadias in the feline species. The first cat was asymptomatic, had a history of bacterial cystitis, and was diagnosed with perineal hypospadias at an appointment for preoperative evaluation of orchiectomy. The second cat had clinical signs of dysuria and pollakiuria for 30 days and had glandular hypospadias. Both cats showed abnormalities in the urinalysis which were suggestive of lower urinary tract disease. For both cases, clinical treatment with antibiotic therapy was performed. In the first patient, surgical treatment consisted of orchiectomy, while in the second animal a perineal urethrostomy and orchiectomy were performed. The cats had a satisfactory recovery after the treatments. Performing a thorough physical examination is essential to diagnose cases of hypospadias and choose the best treatment for each patient.

Large prostatic utricle cyst with calculus in a child: a rare entity

Introduction: Prostatic utricle cyst (PUC) is a rare entity associated with congenital urogenital anomalies. In some cases, prostatic utricle is strikingly enlarged and present as a cystic lesion in perineum or in pelvic cavity posing diagnostic dilemma. Very few case reports are available in the published literature. Case report: We report a case of 12 year old male with complaints of post void dribbling of urine since birth and feeling of incomplete emptying. Clinical examination revealed ambiguous genitalia with perineal hypospadias and bilateral undescended testes. Ultrasound pelvis revealed a well-defined midline cystic lesion posterior to the urinary bladder with an intra-lesional calculus. MRI demonstrated a narrow communication tract between the cystic lesion and posterior urethra suggesting the possibility of PUC. Complete excision of the cyst was performed with ligation of the communicating tract and subsequent histo-pathological examination confirmed prostatic utricle cyst. Postoperative period was uneventful with complete resolution of the pre-operative symptoms. None of the symptoms recurred on follow up of the patient after three month of surgery. Conclusion: Prostatic utricle cyst should always be kept in the differential diagnosis of midline cystic lesions in young males specially if associated with uro-genital anomalies. Thorough clinical and imaging evaluation is needed to establish the diagnosis. MRI is the imaging modality of choice to differentiate utricle cyst from other midline cystic lesions of the pelvis.

PMON312 A De Novo Heterozygous Nonsense Variant In The SEC31A Gene Associated With Pituitary Hormone Deficiency And Disorders Of Sex Development.

Abstract Introduction XYdisorders of sex development (DSD) result from variants in many different human genes but frequently have no detectable molecular cause. In approximately 25% of cases of XY DSD, the index case may have associated malformations. Genetic disorders of endoplasmic reticulum (ER) function are increasingly being recognised but have not been associated with DSD or pituitary disorders. Clinical case Three siblings (with unaffected non-consanguineous parents) were reviewed at the tertiary endocrine clinic. Child I was noted at birth to have cliteromegaly. Imaging and examination under anaesthetic revealed a normal vagina and uterus but gonads of indeterminate origin. She was 46,XY and basal endocrine investigations at the age of 4 years showed a low AMH for male but otherwise normal gonadal and thyroid function and normal IGF-1. She had a laparoscopic bilateral gonadectomy aged 5 years. Pathology demonstrated bilateral testicular tissue, with substantial fibrotic atrophic change and occasional placental alkaline phosphatase (PLAP) positive cells, suggestive of germ cell tumours. Aged 8 years she developed obesity and later hypertension. Child II was reviewed due to short stature and diagnosed with GH deficiency aged 2 years. She has normal adrenal and thyroid function and gonadotrophins. MRI demonstrated an ectopic posterior pituitary. Child III presented with perineal hypospadias, a small phallus, bilateral undescended testes and craniofacial abnormalities. Endocrine investigations revealed hypogonadotrophic hypogonadism, with no testosterone response to hCG stimulation, a low normal AMH and no response of LH or FSH on LHRH stimulation. He has panhypopituitarism with an ectopic posterior pituitary gland on MRI and is currently on treatment with GH, hydrocortisone and levothyroxine. His BP is on the 98th centile for age and height. Child I and Child III have mild developmental delay but are in mainstream school with additional educational support. High-throughput DNA sequencing revealed, in all three siblings, a heterozygous truncating variant in the SEC31A gene that encodes a component of the COPII-complex that coats the vesicles mediating ER to Golgi transport. CRISPR-Cas9 targeted knockout of the corresponding Sec31a region resulted in embryonic lethality in homozygous mice. mRNA phenotyping of ER-related genes demonstrated increased mRNA expression of ATF4 and CHOP in the affected children, genes encoding key ER stress-related proteins, associated with defective protein transport. Conclusions Dysregulation ofanterograde and retrograde COPII-coated-vesicle ER-Golgi transport is increasingly recognised to underlie human developmental disorders, including Craniolenticulosutural dysplasia (OMIM 607812) and Saul-Wilson syndrome (OMIM 618150). The de novo SEC31A nonsense variant in all three affected siblings, the ER stress response, plus reported developmental syndromes with dysfunction of this transport mechanism and evidence from the preclinical mouse model suggest that SEC31A might underlie a previously unrecognised clinical syndrome comprising DSD, endocrine abnormalities, dysmorphic features and developmental delay. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

ODP381 Changes in Perceptions of Pediatric Endocrinologists (PE) and Urologists (PU) to Infants and Children regarding care of individuals with 46,XY DSD

Abstract Introduction Over recent decades, controversy regarding standards of care has contributed to questioning past management recommendations for infants and children with a 46,XY DSD. Surveys conducted in 3 waves (2003, 2010, 2020) provide evidence of changes in recommendations for care have changed over this period. Methods Online surveys of the members of the Pediatric Endocrine Society (PE) and Societies for Pediatric Urology (PU) included case vignettes representing partial androgen insensitivity syndrome (PAIS), micropenis resulting from primary testicular failure, and penile ablation (non-DSD). Survey items included questions regarding recommended gender of rearing (GoR), genital surgery (and timing), and disclosure of diagnostic details to patient. Results The newborn PAIS vignette included elevated LH and FSH and a 1.2 cm. phallus that increased to 1.7 after exogenous testosterone. Male GoR was chosen by 47, 55 &amp; 55% PE and 81, 83 &amp; 69% of PU in waves 1 to 3, respectively; 27 PE and 28% PU chose an added "non-binary" option in 2020. The recommendation that parents, rather than patients, should decide about perineal hypospadias repair was chosen by 70, 60 &amp; 50% of PE and 93, 90 &amp; 79% of PU. Recommending against surgery were 25, 22 &amp; 10% PE and 23, 13 &amp; 8% PU. Recommending surgery be completed at &amp;lt;1 year of age: 56, 59, 66% PE and 69, 78, 84% PU. Recommendation against disclosure of the underlying condition to the patient 12, 17 &amp; 28% PE and 17, 19 &amp; 22% PU, while 35, 28 to 32% PE and 34, 43 &amp; 30% PU recommended that disclosure occur by 11 years of age. For the penile ablation vignette, 78, 92 &amp; 92% PE and 98, 95 &amp; 97% PU recommended male GoR. The 2020 non-binary option was chosen by 4 and 2% PE and PU. The majority of both groups recommended male GoR for the micropenis vignette with testicular failure; 94, 94 &amp; 89% PE and 96, 97 &amp; 88% PU. The decline in 2020 resulted from the recommendation of the non-binary option by 9% PE and 8% PU. Conclusions It seems clear that a female GoR recommendation is currently rare across 46,XY vignettes with evidence of testicular function during at least some of fetal life. It is also apparent that the current emphasis/controversy regarding GoR has resulted in confusion as to how to apply this poorly understood concept. The resulting shift of delaying decisions regarding surgery until the patient can decide is inconsistent with the recommendation that hypospadias repair occur before age 1 year. Finally, lack of or delayed disclosure is inconsistent with patient centered care recommendations. Presentation: No date and time listed

Congenital perineal defect with rectal duplication and extreme hypospadias\u2014a rare association

BackgroundCongenital perineal hernia is an extremely rare entity with only 10 cases having been reported in literature. We report a newborn with exposed bowel loops coming out through a defect in the perineum to the right of the median raphe and propose the term perineoschisis for this abnormality. The exposed bowel loops were a sequestered segment of colon. The baby also had extreme perineal hypospadias and left undescended testis.Case presentationA term neonate, born of caesarean section, was noted at birth to have exposed bowel loops visible in the perineum. The bowel loops were not covered by any membrane. To avoid injury to the exposed bowel loops and setting in of infection, the baby was taken up for emergency surgery. At laparotomy, the bowel loops were traced from duodeno–jejunal junction to ileocecal junction and sigmoid colon and rectum. No loops were seen herniating outside from the abdomen through the perineum opening. The extruded bowel loops were sequestered and ending blindly close to the rectum. The sequestered bowel loops were excised completely and perineum reconstruction was done.ConclusionThe extruded bowel loops would appear to be a form of colonic duplication with the duplicated colonic loops herniating outside through an opening in the perineum. Since the bowel loops were lying to the right of median raphe and were not covered by hernia sac or any other membrane we propose the term perineoschisis for this abnormality. The baby also had extreme hypospadias with a perineal meatus, bifid scrotum and penoscrotal transposition. This association of herniated duplicated colon with extreme hypospadias is hitherto unreported to the best of our knowledge.

The urethral plate and the underlying tissue; a histological and histochemical study

To examine the urethral plate and the underlying tissues in children with proximal hypospadias associated with severe chordee. The urethral plate and the underlying tissue specimens were excised to correct severe chordee in 17 children with proximal and perineal hypospadias with severe chordee. The median age was 20 months (range 8-36). Sections samples were marked and examined from proximal to distal. Specimens were examined histologically using hematoxylin-eosin (H/E) and Elastic van Gieson (EvG) stain. Histochemical examination was also performed using smooth muscle actin (SMA) and factor 8 antibodies. For control, samples from four patients with hypoplastic urethra proximal to the meatus including the hypoplastic segments until the normal urethra were taken. In addition, the urethra of an adult patient with penile tumor was used as control. The average size of the 17 tissue samples was 0.5cm×0.5cm x 0.3cm in depth. There was a common pattern that was seen in all the 17 specimens with a variable degree of expression. H/E staining showed that the epithelial lining changed from pseudostratified epithelium at the proximal intact urethra to non-keratinized stratified squamous epithelium at the urethral meatus to keratinized stratified squamous epithelium distally at the urethral plate level. EvG staining showed overall very few elastic fibres that increased slightly in the distal urethral plate. SMA staining showed a circular pattern of smooth muscle cells in the proximal intact urethra that changed to a U-shaped pattern at the level of the meatus, to a triangle shaped pattern just distal to the meatus. The distal urethral plate showed an irregular, disorganized rather flat pattern of the smooth muscles. Factor 8 antibodies staining the blood spaces revealed dysplastic unorganized large blood sinusoids underneath the urethral plate that were different from normal capillaries surrounding the proximal urethra. The urethral plate and the underlying tissues in patients with severe chordee have different structure from normal urethra as compared to available literature and the adult control patient. The lack of elastic fibres may help to explain the rigidity of the ventral penis causing chordee. The disorganized irregular distribution of the smooth muscle fibres is suggestive of the hypoplastic corpus spongiosum. The abnormal large blood sinusoids may explain the poor healing quality of the ventral penis in patients with perineal and proximal patients associated with severe chordee. This may explain persistent/recurrent chordee observed later in those patients with severe chordee when dorsal plication is used. The study also supports the recent trend of 2 stage procedure as a plan of management for patients with proximal and perineal hypospadias with severe chordee and excision of all the dysplastic tissues during the first operation.

Tunneled tubularized bladder mucosal grfaft for long urethral reconstruction: is it a reliable option in selected complex cases in children and adolescents?

Aim: We analyzed the use of tubularized tunneled bladder mucosa graft (TBMG) and its application as a salvage procedure or as primary surgery for long urethroplasty in children and adolescents. Specific attention was given to a new method to harvest a long bladder mucosa graft through a minimal detrusotomy. Methods: We analyzed the files of 10 patients who underwent TBMG urethroplasty at median age of 105 months (range 20-195 months). The indications were perineal hypospadias cripple in two, masculinizing genitoplasty for ovotesticular Ovotesticular Disorder of Sex Development (DSD) in two, perineal hypospadias in four, duplicated urethra in one, and complications of circumcision in one. Staged reconstruction was performed in all patients. The first stage was removal of all fibrous tissues and efficient treatment of curvature and skin coverage. After a minimal delay of one year, a free bladder mucosa graft was harvested through a minimal detrusotomy and tubularized. Tunneling of the graft was proceeded from the perineal urethrostomy to the glans. Results: The graft was successfully harvested through the minimal detrusotomy approach for variable lengths of urethroplasty; the median length was 10.5 cm (range 8-16 cm). The median follow up was 61.7 months (range 18-160 months). TBMG was the last surgery with no redo in five cases (50%). Long stricture occurred in one case of primary perineal hypospadias and needed a redo staged surgery. Two patients performed self-dilatation for distal stenosis. Conclusion: The tunneled bladder mucosa tube graft technique represents a good alternative for a long urethroplasty in patients with a paucity of healthy skin. The minimal detrusotomy technique for graft retrieval may reduce graft harvesting morbidity.