De novo variants identified by trio whole exome sequencing of bladder exstrophy epispadias complex.

Bladder exstrophy epispadias complex (BEEC) encompasses a spectrum of conditions ranging from mild epispadias to the most severe form: omphalocele-bladder exstrophy-imperforate anus-spinal defects (OEIS). BEEC involves abnormalities related to anatomical structures that are proposed to have a similar underlying etiology and pathogenesis. In general, BEEC, is considered to arise from a sequence of events in embryonic development and is believed to be a multi-etiological disease with contributions from genetic and environmental factors. Several genes have been implicated and mouse models have been generated, including a knockout model of p63, which is involved in the synthesis of stratified epithelium. Mice lacking p63 have undifferentiated ventral urothelium. MNX1 has also been implicated. In addition, cigarette smoking, diazepam and clomid have been implied as environmental factors due to their relative association. By in large, the etiology and pathogenesis of human BEEC is unknown. We performed de novo analysis of whole exome sequencing (WES) of germline samples from 31 unrelated trios where the probands have a diagnosis of BEEC syndrome. We also evaluated the DECIPHER database to identify copy number variants (CNVs) in genes in individuals with the search terms "bladder exstrophy" in an attempt to identify additional candidate genes within these regions. Several de novo variants were identified; however, a candidate gene is still unclear. This data further supports the multi-etiological nature of BEEC.

Urothelial Differences in the Exstrophy-Epispadias Complex: Potential Implications for Management.

PURPOSE: The authors examined the urothelium of exstrophy-epispadias complex spectrum patients for histological differences and expression of terminal markers of urothelial differentiation. MATERIALS AND METHODS: Between 2012 and 2017 bladder biopsies were obtained from 69 pediatric exstrophy-epispadias complex patients. These specimens were compared to bladder specimens from normal controls. All bladder specimens underwent histological assessment followed by immunohistochemical staining for uroplakin-II and p63. Expression levels of uroplakin-II and p63 were then assessed by a blinded pathologist. RESULTS: Forty-three classic bladder exstrophy biopsies were obtained (10 newborn closures, 22 delayed closures, and 11 repeat closures). Additional biopsies from 18 cloacal exstrophy patients and 8 epispadias patients were also evaluated. These specimens were compared to 8 normal control bladder specimens. Overall, uroplakin-II expression was lower in exstrophy-epispadias complex patients compared to controls (p <0.0001). Among classic bladder exstrophy patients, there was reduced expression of uroplakin-II in the delayed and repeat closures in comparison to newborn closures (p=0.045). Expression of p63 was lower in patients with exstrophy-epispadias complex compared to controls (p <0.0001). Expression of p63 was similar among classic bladder exstrophy patients closed as newborns when compared to delayed or repeat closures. Classic bladder exstrophy patients had a higher rate of squamous metaplasia when compared to controls (p=0.044). Additionally, there was a higher rate of squamous metaplasia in the patients undergoing delayed closure in comparison to those closed in the newborn period (p <0.001). CONCLUSIONS: The urothelium in the exstrophy-epispadias complex bladder is strikingly different than that of healthy controls. Uroplakin-II expression is greatly reduced in exstrophy-epispadias complex bladders and is influenced by the timing of bladder closure. Reduced uroplakin-II expression and increased rates of squamous metaplasia in exstrophy-epispadias complex patients undergoing delayed closure suggests that exposure of the urothelium may induce these changes. These findings shed light on the molecular changes in exstrophy-epispadias complex bladders and may have implications on the appropriate timing of primary bladder closure, as those closed in the newborn period appear to have a greater potential for growth and differentiation.

Is there a shortening of the urethral plate in complete penile disassembly used in epispadias repair, and what is its impact on the final outcomes?

PURPOSE: To assess the importance of shortening of the urethral plate that occurred with complete penile disassembly technique in epispadias repair and its impact on cosmetic and functional results (on urinary incontinence). METHODS: From January 2009 to December 2016, 26 boys underwent complete penile disassembly technique for proximal epispadias repair. Twenty-one patients had epispadias after primary repair of bladder exstrophy, and 5 patients had isolated penopubic epispadias. The age of the patients ranged from 11 months to 6 years (median 3 years). RESULTS: After disassembling the penis in three parts, the shortening and narrowing of urethral plate were found in all patients; the shortening varied between 2 and 16 mm. However, in isolated epispadias, the urethral plate is easily extensible. The cosmetic results (after dehiscence and fistulas repair) were found to be satisfactory in 24 patients with conical glans and meatus in the orthotopic position without any necrosis of the glans. However, 18 patients (81.8% of cases) who initially had a bladder exstrophy presented a dehiscence or fistula. The urinary continence ≥ 1 h was observed in 5 patients (19% of cases), and only 3 patients (11.5% of cases) had a urinary continence ≥ 3 h. CONCLUSIONS: The complete penile disassembly procedure restores the normal anatomy of the penis. Despite the shortening and narrowing of the urethral plate, the cosmetic results were good in the majority of patients. However, its functional outcomes on urinary incontinence, particularly for epispadias with bladder exstrophy, remain uncertain.

Preoperative care of Polypoid exposed mucosal template in bladder exstrophy: the role of high-barrier plastic wraps in reducing inflammation and polyp size

ABSTRACT Objective To assess the role of high-barrier plastic wrap in reducing the number and size of polyps, as well as decreasing the inflammation and allergic reactions in exstro- phy cases, and to compare the results with the application of low-barrier wrap. Materials and Methods Eight patients with bladder exstrophy-epispadias complex (BEEC) that had used a low density polyethylene (LDPE) wrap for coverage of the exposed polypoid bladder in preoperative care management were referred. The main complaint of their parents was increase in size and number of polyps. After a period of 2 months using the same wrap and observing the increasing pattern in size of polyps, these patients were recommended to use a high-barrier wrap which is made of polyvinylidene chloride (PVdC), until closure. Patients were monitored for the number and size of polyps before and after the change of barriers. The incidence of para-exstrophy skin infection/inflammation and skin allergy were assessed. Biopsies were taken from the polyps to identify histopathological characteristics of the exposed polyps. Results The high barrier wrap was applied for a mean ± SD duration of 12±2.1 months. Polyps' size and number decreased after 12 months. No allergic reaction was detected in patients after the usage of PVdC; three patients suffered from low-grade skin allergy when LDPE was applied. Also, pre-malignant changes were observed in none of the patients in histopathological examination after the application of PVdC. Conclusion Polyps' size and number and skin allergy may significantly decrease with the use of a high-barrier wrap. Certain PVdC wraps with more integrity and less evaporative permeability may be more "exstrophy-friendly".

A Model for Sustained Collaboration to Address the Unmet Global Burden of Bladder Exstrophy-Epispadias Complex and Penopubic Epispadias: The International Bladder Exstrophy Consortium.

Importance: International collaboration to alleviate the massive burden of surgical disease is recognized by World Health Organization as an urgent need, yet the surgical mission model to treat reconstructive surgical challenges is often constrained in ensuring adequate patient follow-up, optimal outcomes, and sustainability. Objective: To determine whether a collaboration predicated on long-term commitment by surgeons returning to the same institution annually combined with an experienced host surgical team and infrastructure to ensure sustained patient follow-up could provide surgical care with acceptable outcomes to treat bladder exstrophy-epispadias complex (BE) and penopubic epispadias (PE). Design, Setting, and Participants: In this prospective, observational study, long-term collaboration was created and based at a public hospital in Ahmedabad, India, between January 2009 and January 2015. The entire postoperative cohort was recalled in January 2016 for comprehensive examination, measurement of continence outcomes, and assessment of surgical complications. Seventy-six percent of patients (n = 57) who underwent complete primary repair of exstrophy during the study interval returned for annual follow-up in 2016 and formed the study cohort: 23 patients with primary BE, 19 patients with redo BE, and 11 patients with PE repair. Main Outcomes and Measures: Demographics, operative techniques, and perioperative complications were recorded. A postoperative protocol outlining procedures to ensure monitoring of study participants was followed including removal of ureteral stents, urethral catheter, external fixators, imaging, and patient discharge. Results: Of the 57 patients, 4 were excluded because they underwent ureterosigmoidostomy. Median age at time of surgery was 3 years (primary BE), 7 years (redo BE), and 10 years (PE), with median follow-up of 3 years, 5 years and 3 years, respectively; boys made up more than 70% of each cohort (n = 17 for primary BE, n = 15 for redo BE, and n = 9 for PE). All BE and 3 PE repairs (27%) were completed with concurrent anterior pubic osteotomies. Seventeen of 53 patients (32%) experienced complications. Only 1 patient with BE (4%) had a bladder dehiscence and was repaired the following year. Conclusions and Relevance: A unique surgical mission model consisting of an international collaborative focused on treating the complex diagnoses of BE and PE offers outcomes comparable with those in high-income countries, demonstrating a significant patient retention rate and an opportunity to rigorously study outcomes over an accelerated interval owing to the high burden of disease in India. Postoperative care following a systematized algorithm and rigorous follow-up is mandatory to ensure safety and optimal outcomes.

Preoperative care of Polypoid exposed mucosal template in bladder exstrophy: the role of high-barrier plastic wraps in reducing inflammation and polyp size.

OBJECTIVE: To assess the role of high-barrier plastic wrap in reducing the number and size of polyps, as well as decreasing the inflammation and allergic reactions in exstrophy cases, and to compare the results with the application of low-barrier wrap. MATERIALS AND METHODS: Eight patients with bladder exstrophy-epispadias complex (BEEC) that had used a low density polyethylene (LDPE) wrap for coverage of the exposed polypoid bladder in preoperative care management were referred. The main complaint of their parents was increase in size and number of polyps. After a period of 2 months using the same wrap and observing the increasing pattern in size of polyps, these patients were recommended to use a high-barrier wrap which is made of polyvinylidene chloride (PVdC), until closure. Patients were monitored for the number and size of polyps before and after the change of barriers. The incidence of para-exstrophy skin infection/inflammation and skin allergy were assessed. Biopsies were taken from the polyps to identify histopathological characteristics of the exposed polyps. RESULTS: The high barrier wrap was applied for a mean ± SD duration of 12±2.1 months. Polyps' size and number decreased after 12 months. No allergic reaction was detected in patients after the usage of PVdC; three patients suffered from low-grade skin allergy when LDPE was applied. Also, pre-malignant changes were observed in none of the patients in histopathological examination after the application of PVdC. CONCLUSION: Polyps' size and number and skin allergy may significantly decrease with the use of a high-barrier wrap. Certain PVdC wraps with more integrity and less evaporative permeability may be more "exstrophy-friendly".

Congenital prepubic sinus (an epispadiac variant of dorsal urethral duplication) with dorsal penile curvature in an adult man: a rare association.

Urethral duplication is among a very rare congenital disorder with multiple anatomical variants reported. Urethral duplication of complete type is usually diagnosed during childhood with urinary incontinence or double urinary stream as common presentation. However, patients with incomplete urethral duplication usually present with intermittent mucous discharge from the accessory urethral opening. A 20-year-old man presented to us with intermittent mucous discharge from the accessory opening along with dorsal penile curvature making sexual intercourse very difficult. The epispadiac urethral tract with proximal fibrous tract was excised, and the dorsal penile curvature was corrected by ventral plication, implicating that the fibrous cord may be the causative factor for the development of dorsal curvature.

[Isolated male epispadias]. / Epispadias masculin isolé.

Epispadias is a rare urogenital malformation characterized by more or less complete aplasia of the upper part of the urethra. It is commonly associated with bladder exstrophy. Isolated epispadias occurs in 10% of cases. Continent and incontinent epispadias may be distinguished. We report the case of a 29-year old patient presenting with dysuria associated with the impossibility of having sexual intercourses. Physical examination of the external genitalia showed slit-like abnormal urethral opening on the distal half of the dorsal side of the penis. Patient's penis didn't have dorsal curvature (chordee), the corpus cavernosum was palpated and slightly lateralized. The abdominal wall was without abnormalities. The remainder of the clinical examination was normal. Given this anomaly, the diagnosis of balano-pubic continent epispadias was retained. Ultrasound of the urinary tract was normal and pelvis X-ray without preparation showed interpubic diastasis. The patient underwent single-stage surgery using Cantwell-Young technique. Immediate postoperative outcome was without abnormalities; the urethral probe was removed 21 days later, after wound healing. Functional and aesthetics outcome evaluated at three and six months was satisfactory without penis shortness.

Concealed epispadias associated with a buried penis.

OBJECTIVE: The aim was to describe the clinical presentation and the surgical management of penile epispadias associated with a buried penis in five children. PATIENTS AND METHODS: This is a 5-year retrospective review of patients presenting with a buried penis, a congenital defect of the penile skin shaft associated with an unretractable foreskin for whom a penile epispadias was found at the time of surgery. All had undergone surgery combining a Cantwell-Ransley procedure and refashioning of the penile skin following the authors' technique. RESULTS: Three children had a glanular epispadias and two had a midshaft epispadias. Four had a satisfactory outcome, and one required a complementary urethroplasty for glanular dehiscence. CONCLUSION: Buried penis and epispadias are usually isolated congenital anomalies, although they can be associated. It is therefore recommended to warn parents about the possibility of underlying penile anomaly in children with buried penises and unretractable foreskin. Careful palpation of the dorsum of the glans through the foreskin looking for a dorsal cleft could indicate an associated epispadiac urethra. Surgical correction of both anomalies can be done at the same time. Parents of boys with buried penises should be warned that underlying penile anomaly may exist.

Isolated Male Epispadias: Anatomic Functional Restoration Is the Primary Goal.

Background. Isolated male epispadias (IME) is a rare congenital penile malformation, as often part of bladder-exstrophy-epispadias complex (BEEC). In its isolated presentation, it consists in a defect of the dorsal aspect of the penis, leaving the urethral plate open. Occurrence of urinary incontinence is related to the degree of dorsal displacement of the meatus and the underlying underdevelopment of the urethral sphincter. The technique for primary IME reconstruction, based on anatomic restoration of the urethra and bladder neck, is here illustrated. Patients and Methods. A retrospective database was created with patients who underwent primary IME repair between June 1998 and February 2014. Intraoperative variables, postoperative complications, and outcomes were assessed. A descriptive statistical analysis was performed. Results and Limitations. Eight patients underwent primary repair, with penopubic epispadias (PPE) in 3, penile epispadias (PE) in 2, and glandular epispadias (GE) in 3. Median age at surgery was 13.0 months [7-47]; median follow-up was 52 months [9-120]. Complications requiring further surgery were reported in two patients, while further esthetic surgeries were required in 4 patients. Conclusion. Anatomical restoration in primary IME is safe and effective, with acceptable results given the initial pathology.

PLAGL1 epimutation and bladder exstrophy: Coincidence or concurrent etiology?

BACKGROUND: The bladder exstrophy-epispadias complex (BEEC) is characterized by a spectrum of genitourinary malformations. Both classical bladder exstrophy and the most severe phenotype, exstrophy of the cloaca, display omphaloceles, a cardinal anomaly of some disorders caused by altered imprinting. Therefore, we hypothesized that BEEC in some patients could occur on the basis of an undiagnosed imprinting disorder. Such altered imprinting is associated with changes in the parent-of-origin-specific DNA methylation. METHODS: We analyzed the DNA methylation of 54 imprinted loci in 23 selected patients with different BEEC subtypes (epispadias n = 1, classical bladder exstrophy n = 10, exstrophy of the cloaca n = 12) using the Infinium HumanMethylation450 BeadChip. A total of 471,722 not imprinted autosomal CpG loci and 891 imprinted CpG loci were investigated. Findings were corroborated by methylation-specific-multiplex ligation-dependent probe amplification (MS-MLPA) and microsatellite analysis. RESULTS: No significant differences in the DNA methylation of the not imprinted and imprinted CpG were observed depending on subtype of BEEC. Nevertheless, in 1 of the 23 patients who displayed a classical bladder exstrophy, we detected hypomethylation of the imprinted PLAGL1 locus in chromosome 6q24. We verified this hypomethylation by MS-MLPA and showed further the methylation loss to be caused most likely by a mosaic epimutation. CONCLUSION: Considering that it is highly unlikely to detect a PLAGL1 epimutation among 23 individuals given the low incidence of this alteration in the population, our observations further support a link between BEEC and imprinting disorders. Birth Defects Research (Part A) 106:724-728, 2016. © 2016 Wiley Periodicals, Inc.

Concealed Epispadias: Report of Two Cases and Review of Literature.

OBJECTIVE: To present an overview of the clinical presentation and pathological anatomy of epispadias with intact prepuce--a rare condition that has only occasionally been reported in literature. MATERIALS AND METHODS: We present two cases of concealed epispadias. We also review the available literature with regard to this rare condition. We found 14 cases in 7 studies that were reviewed. Relevant variables were reviewed and are discussed. RESULTS: There were 13 of 16 cases presented with complaints of buried or webbed penis. In 11 of 16 cases, epispadias was suspected or diagnosed at first presentation and could be surgically corrected in the first intervention. Epispadias repair was successful with regard to cosmesis and erectile function in all cases, including ours. CONCLUSION: Proper preoperative diagnosis and preoperative counseling of parents are essential for the successful treatment of this rare entity. Fewer complications, less additional interventions, and better continence rates seem to be noted for the boys with epispadias and intact prepuce.

[THE METHOD OF COLPOPOIESIS IN AN URINARY BLADDER EXTROPHY].

Complex of extrophy--epispadias--a rare inborn malformation of genitourinary system, abdominal wall muscles and pelvic bones. The observation was adduced, concerning an urinary bladder extrophy in a girl in combination with vaginal agenesia after noneffective primarily--postponed closure of urinary bladder, osteotomy (in the age of 4 yrs old), with consequent ureterosygmostomy. In the patient there was conducted a reconstructive operation for vagina creation, using nonfunctioning bladder, right-sided nephrectomy for severe ureterohydronephrosis, reconstruction of anterior abdominal wall and external genitalia.

The surgical management of male epispadias in the new millennium.

Male epispadias is a rare and challenging urologic condition. As part of the epispadias-exstrophy complex of genitourinary anomalies, it covers a broad spectrum with the mildest forms being the rarest. The anatomic classification into glanular, penile, and penopubic is based on the location of the urethral meatus. However, this classification fails to include some of the suprapubic malformations that may be present such as pubic diastasis, bladder neck abnormalities, and vesicoureteral reflux. Careful preoperative evaluation should allow the identification of these anomalies and will help achieve the goals of surgical reconstruction. These goals include cosmetic and functional reconstruction of the penis and urethra as well as, when needed, creation of a continence mechanism that will allow for normal bladder function, storage, and evacuation of urine. This review will focus on: 1) the preoperative evaluation and management of male patients with epispadias and 2) surgical management based on the anatomic classification.

2D and 3D MRI features of classic bladder exstrophy.

The bladder exstrophy-epispadias complex (EEC) represents a spectrum of rare and surgically correctable congenital anomalies. Classic bladder exstrophy (CBE) stands between epispadias and cloacal exstrophy (CE) in the severity spectrum, and is the most commonly encountered type. CBE involves congenital defects of the bladder, abdominal wall, pelvic floor, and bony pelvis. With the growing understanding of the detrimental effects of radiation in children, magnetic resonance imaging (MRI) is progressively been utilized in the preoperative work-up and post-surgical follow-up of these patients. MRI provides valuable information for planning and evaluating the optimal surgical techniques for closure of CBE. The aim of this paper is to provide a review of the two- (2D) and three-dimensional (3D) MRI features of CBE including a detailed analytical description of the anatomy of the pelvic floor in affected patients.

Surgical anatomy of penis in exstrophy-epispadias: a study of arrangement of fascial planes and superficial vessels of surgical significance.

OBJECTIVE: To study the anatomic arrangement of the fascial planes and superficial vessels in relationship to the laid-open urethral plate, glans, corpus spongiosum, and corpora cavernosa in the penis of patients with exstrophy or epispadias. MATERIALS AND METHODS: Of 6 patients, 4 had classic exstrophy and 2 had incontinent epispadias. These patients had presented beyond adolescence without previous intervention and were selected for the present study. Using a 1.5-T magnetic resonance imaging scanner and compatible 3-in. surface coil, the epispadiac penises were studied using fast spin echo sequences and contrast-enhanced sequences. In 2 patients, angiography of the superficial vessels was also performed using multidetector row helical computed tomography. The imaging findings were also verified during the subsequent reconstructive surgery. RESULTS: A clear demarcation of the skin, dartos fascia, Buck's fascia, corpora cavernosa, corpus spongiosum, and the intraglanular planes were seen with the course of the blood vessels. The penile dartos received axial pattern vessels from the external pudendal vessels, with collateral branches from the dorsal penile artery as transverse branches at the shaft of the penis and preputial branches at the coronal sulcus. Buck's fascia sleeved the corpora cavernosa, enveloped the neurovascular bundle, and fused with the corpus spongiosum without crossing the midline. Intraglanular extension of Buck's fascia separated the intraglanular vascular arcade from the tip of the corpora. CONCLUSION: Parallel to the ventral midline, axial pattern vessels to the skin-dartos complex are present, with an additional supply to the prepuce from the terminal penile arteries. These findings can be used for designing the skin coverage. The subfascial plane between the tip of the corpora and the intraglanular vascular arcade and the plane of cleavage between the cavernosa-spongiosum interface can be used for efficient corporal urethral separation.

Unusual duplicate bladder exstrophy in a female newborn: a case report.

The authors report a rare variant of exstrophy-epispadias complex, a duplicate bladder with normal bladder communicating with an exstrophic bladder by a fistula, in a girl with no genital malformation except for a duplicated clitoris. This variant could be a hybrid form of duplicate bladder exstrophy and superior vesical fistula. It seems easier to repair and has a better prognosis than classic bladder exstrophy.

Insertion/deletion polymorphisms in the ΔNp63 promoter are a risk factor for bladder exstrophy epispadias complex.

Bladder exstrophy epispadias complex (BEEC) is a severe congenital anomaly; however, the genetic and molecular mechanisms underlying the formation of BEEC remain unclear. TP63, a member of TP53 tumor suppressor gene family, is expressed in bladder urothelium and skin over the external genitalia during mammalian development. It plays a role in bladder development. We have previously shown that p63(-/-) mouse embryos developed a bladder exstrophy phenotype identical to human BEEC. We hypothesised that TP63 is involved in human BEEC pathogenesis. RNA was extracted from BEEC foreskin specimens and, as in mice, ΔNp63 was the predominant p63 isoform. ΔNp63 expression in the foreskin and bladder epithelium of BEEC patients was reduced. DNA was sequenced from 163 BEEC patients and 285 ethnicity-matched controls. No exon mutations were detected. Sequencing of the ΔNp63 promoter showed 7 single nucleotide polymorphisms and 4 insertion/deletion (indel) polymorphisms. Indel polymorphisms were associated with an increased risk of BEEC. Significantly the sites of indel polymorphisms differed between Caucasian and non-Caucasian populations. A 12-base-pair deletion was associated with an increased risk with only Caucasian patients (p = 0.0052 Odds Ratio (OR) = 18.33), whereas a 4-base-pair insertion was only associated with non-Caucasian patients (p = 0.0259 OR = 4.583). We found a consistent and statistically significant reduction in transcriptional efficiencies of the promoter sequences containing indel polymorphisms in luciferase assays. These findings suggest that indel polymorphisms of the ΔNp63 promoter lead to a reduction in p63 expression, which could lead to BEEC.

Covered exstrophy with ectopic intestinal tissue and bifid phallus: one-stage repair of a complex abnormality.

Variant presentations of the exstrophy-epispadias complex are rare congenital malformations, such as covered exstrophy with bifid phallus. We describe a male neonate with covered exstrophy with an intestinal remnant and epispadiac bifid phallus. We report this case to emphasize the simultaneous successful repair of bifid phallus and exstrophy in this rare complex abnormality.

Pelvic-floor imaging using three-dimensional ultrasonography and magnetic resonance imaging in the long term follow-up of the bladder-exstrophy-epispadias complex.

OBJECTIVE: To investigate whether established pelvic floor variables can be used to predict the risk of uterine prolapse after surgery and to compare two different operative strategies, pelvic adaptation with functional reconstruction and an open pelvis with urinary diversion, as a congenital bony pelvis and pelvic floor defect predisposes females with bladder-exstrophy-epispadias complex (BEEC) to uterine prolapse. PATIENTS, SUBJECTS AND METHODS: We conducted a cross-sectional study using perineal three-dimensional ultrasonography (3D-US) and magnetic resonance imaging (MRI) to describe pelvic floor anatomy in 19 women with BEEC (mean age 27.3 years) and five controls, with the outcome evaluated by a semi-structured interview. The analysis of 3D-US and MRI was conducted by two independent investigators. RESULTS: Of the 19 women with BEEC, 13 initially had a functional bladder reconstruction, six a urinary diversion with removal of the exstrophic bladder, and 12 women had closure of the pelvis either by traction bandage or osteotomy, and in the other seven the symphysis was not approximated. Four patients had a complete and one a mild uterine prolapse. After a mean follow-up of 24 years, the mean symphyseal diastasis was 4.5 cm after symphyseal approximation, 9.0 cm without symphyseal approximation in BEEC and 0.49 cm in controls. The mean levator hiatus was 4.9 cm on 3D-US and 4.1 cm on MRI after symphyseal approximation, 5.9 and 7.6 cm without symphyseal approximation and 4.2 and 3.2 cm in controls, respectively. The respective mean levator angle was 86.6 degrees and 87.3 degrees after symphyseal approximation, 104.1 degrees and 101.3 degrees without and 71.3 degrees and 45.5 in controls. Prolapse was statistically significantly more common in patients with no symphyseal approximation. CONCLUSION: This is the first study showing that perineal 3D-US is useful for pelvic floor imaging in BEEC. Established pelvic floor variables might be useful for predicting the risk of pelvic organ prolapse in BEEC.