A Modification of the Newborn Operation for Cloacal Exstrophy: Leaving the Cecal Plate Untouched.

The conventional approach to managing a newborn with cloacal exstrophy typically includes separating the cecal plate from between the two hemibladders, tubularizing it to be included in the fecal stream, creating an end colostomy, and bringing the two bladder halves together. This study introduces an alternative approach wherein the cecal plate is retained in its original position and designated for future use as an autoaugment of the bladder. Four cases of cloacal exstrophy cases managed between November 2019 and February 2024 are described, with surgical approach and postoperative outcomes reported. Two patients who underwent traditional reconstruction experienced bacterial overgrowth attributed to stasis in the cecal plate, which manifested in increased ostomy output and feeding intolerance. Treatment in these two cases was to remove the cecum from the fecal stream and use it instead for a bladder augment. Learning from these cases, the third and fourth newborn's approach involved retaining the cecum in situ for autoaugmentation of the bladder and performing an ileal to hindgut anastomosis. No postoperative acidosis occurred in these patients. The alternative approach to the newborn management of cloacal exstrophy whereby the cecal plate is left in situ can decrease stasis and postoperative bacterial overgrowth. It allows for an autoaugmentation of the bladder and is technically easier than the traditional rescue of the cecal plate from within the two hemibladders.

Cloacal Exstrophy Closure Without Osteotomy and Immobilization: A Recipe for Failure.

BACKGROUND: Cloacal exstrophy (CE) remains one of the most severe birth defects compatible with life with a constellation of anomalies involving the bladder, genitalia, hindgut, and spinal cord. Pelvic osteotomy and immobilization have been utilized to facilitate bladder closure, yet their role as adjuncts remains a topic of debate. The authors sought to evaluate the outcomes of CE closure without the use of osteotomy or lower extremity (LE)/pelvic immobilization. METHODS: An institutional database of 173 CE patients was reviewed for patients closed without osteotomy and/or limb immobilization. Patient records were reviewed for continence procedures, reclosure operations, and continence outcomes. RESULTS: A total of 59 closure surgeries that met inclusion criteria were identified in 56 unique patients. Thirty-seven closure procedures developed eventual failure (63%) with secondary closure events also resulting in failure. Most closures did not use an osteotomy, 93.2%. LE immobilization-only was used in most closures (43/59), of which only 37% were successful. Failures were attributed to dehiscence (14/37), bladder prolapse (19/37), or both dehiscence and prolapse (4/37). The median age at closure was 3 days old (1-18.5 IQR) with the majority of closure events (47) closure events taking place in the newborn period. Median diastasis prior to primary closure was 6 cm (4.8-8 cm IQR). The median number of closure attempts needed to close the bladder was 2 (1-2 IQR). Of the 56 patients, 31 have >3 h of daytime continence, with the entirety of these patients catheterizing a stoma or below. CONCLUSION: These results highlight the critical role of osteotomy and lower limb immobilization in successful closure of the bladder and abdominal wall in CE. TYPE OF STUDY: Treatment Study. LEVEL OF EVIDENCE: Level III.

Mental health, psychosocial functioning, and health-related quality of life of children and adolescents with bladder exstrophy, cloacal exstrophy, and epispadias: A scoping review.

BACKGROUND: The exstrophy-epispadias complex (EEC) is a spectrum of rare congenital defects affecting the genitourinary system that includes epispadias, bladder exstrophy, and cloacal exstrophy. EEC patients may require several surgeries throughout their lifetime and experience a number of difficulties that may impact their quality of life (QoL), mental health, and psychosocial functioning. OBJECTIVE: The purpose of this scoping review is to systematically map existing literature that explores the mental health, psychosocial functioning, and QoL of children and adolescents with EEC. STUDY DESIGN: A search strategy on multiple bibliographic databases was created using a combination of Medical Subject Headings (MeSH) and keywords for the concepts of bladder exstrophy, cloacal exstrophy, or epispadias. RESULTS: The initial search identified 6303 unique articles. 254 articles were selected for full-text review, and 76 articles were identified for data extraction. Articles were excluded if they solely focused on adults. 25 articles are included in this review regarding child and adolescent experiences with EEC. DISCUSSION: Many child-focused studies utilized HRQoL measures to explore changes to an individual's quality of life after undergoing specific continence surgeries, with many studies finding improved QoL after surgery. As children age into adolescence, the research also demonstrates that experiences with QoL may change, with additional differences by gender. Body- and self-image seemed to become more of a concern as patients aged into adolescence, with special consideration for cloacal exstrophy patients who often undergo routine neonatal assignment genetic male to female. CONCLUSIONS: The existing literature suggests that current measures do not demonstrate that children and adolescents with EEC function differently than the general population, but children with EEC have a greater likelihood of experiencing a wide range of emotional and behavioral problems as they reach adolescence. Future studies should further explore manifestations of mental health and QoL throughout the life course.

Management of cloacal exstrophy: Experience from tertiary hospital, Tanzania. Case series.

INTRODUCTION AND IMPORTANCE: Cloacal exstrophy (CE) is defined as a complex anomaly that affects the urogenital and intestinal tracts. It is the most serious form of anomaly that is described within the so-called exstrophy-epispadias complex. These malformations usually present a challenge in the management of particular conditions, as most of these forms require multiple surgeries, resulting in the use of multidisciplinary approaches, including reconstructive urologists, pediatric surgeons, orthopedic surgeons, endocrinologists, pediatricians, psychologists and nutritionists. Additionally, these patients present with ambiguous genitalia, which is another aspect that needs to be taken into consideration during the management of this condition. CASE PRESENTATION: The first patient, a baby who was 8 days of life and referred from a peripheral hospital, presented with classic features of cloaca exstrophy. He underwent first-stage cloacal exstrophy repair. The intraoperative findings included a bi-halved bladder and phallus, and the ureters were not appreciated, but there was continuous urine leakage from the bi-halved bladder and no uterus or ovaries. Poorly formed cecum, cecal-cutaneous fistula with an everted part of the terminal ileum protruding outside (mucosa-out), no transverse, no descending colon, collapsing small bowel, left undescended testis in the inguinal region, and right abdominal undescended testis. He first underwent surgery, which involved ileostomy, omphalocele closure and proper bladder exstrophy construction. The second patient, a 6-day-old female, had a similar presentation and physical findings as the first patient did, except that she had elephantoid trunk deformity with a cecal fistula, bifid clitoris, two cervical orifices, and two uteri completely separated with ovaries. Mobilization of the hindgut, closure of the cecal fistula, and proper bladder exstrophy after repair of the posterior wall were performed. The third patient was a 10-day-old female, similar to the second patient, but this patient presented with a left leg deformity with wide diastasis. In this case, the urinary bladder was not bivalved, and the cecal fistula had perforated just below the posterior wall of the urinary bladder. A mild omphalocele, bifid clitoris and vagina, one cervical orifice, and two uteri completely separated, with ovaries observed. Mobilization of the hindgut, closure of the cecal fistula, and proper bladder exstrophy after repair of the posterior wall were performed. The postoperative period was uneventful. CLINICAL DISCUSSION: Surgical management of cloacal exstrophy is typically undertaken in the newborn period (48-72 h) as a combined effort between pediatric surgery and urology. In the setting of associated spinal dysraphism, neurosurgical consultation and closure should be undertaken as soon as the infant becomes medically stable. Early operation minimizes bacterial colonization of exposed viscera and may decrease the need for pelvic osteotomy. The goals of treatment include securing the abdominal wall and bladder closure, preserving renal function, preventing short bowel syndrome, creating functional and cosmetically acceptable genitalia, and attaining acceptable urinary and fecal continence. CONCLUSION: Cloacal exstrophy remains a rare and complex congenital anomaly characterized by an array of anatomical defects affecting multiple organ systems. With respect to the approach of this congenital malformation, it is therefore important that these individuals and their families remain under the care of a multidisciplinary team of providers who can offer medical care, counseling and life-long follow-up.

Ventral body wall closure: Mechanistic insights from mouse models and translation to human pathology.

The ventral body wall (VBW) that encloses the thoracic and abdominal cavities arises by extensive cell movements and morphogenetic changes during embryonic development. These morphogenetic processes include embryonic folding generating the primary body wall; the initial ventral cover of the embryo, followed by directed mesodermal cell migrations, contributing to the secondary body wall. Clinical anomalies in VBW development affect approximately 1 in 3000 live births. However, the cell interactions and critical cellular behaviors that control VBW development remain little understood. Here, we describe the embryonic origins of the VBW, the cellular and morphogenetic processes, and key genes, that are essential for VBW development. We also provide a clinical overview of VBW anomalies, together with environmental and genetic influences, and discuss the insight gained from over 70 mouse models that exhibit VBW defects, and their relevance, with respect to human pathology. In doing so we propose a phenotypic framework for researchers in the field which takes into account the clinical picture. We also highlight cases where there is a current paucity of mouse models for particular clinical defects and key gaps in knowledge about embryonic VBW development that need to be addressed to further understand mechanisms of human VBW pathologies.

Cloacal Exstrophy with Normal Penis and Urethra - A Rare Variant.

Classically, cloacal exstrophy presents with omphalocele, bladder exstrophy, imperforate anus, and spinal defects. We report a rare variant of cloacal exstrophy in a 6-day-old male with an intact lower abdominal wall, normal penis, and urethra. Only two such cases have been reported in the literature.

Updates on the Care of Cloacal Exstrophy.

Cloacal exstrophy is the most severe congenital anomaly of the exstrophy-epispadias complex and is characterized by gastrointestinal, genitourinary, neurospinal, and musculoskeletal malformations. Individualized surgical reconstruction by a multidisciplinary team is required for these complex patients. Not infrequently, patients need staged surgical procedures throughout childhood and adolescence. Following significant improvements in medical care and surgical reconstructive techniques, nearly all patients with cloacal exstrophy now survive, leading to an increased emphasis on quality of life. Increased attention is given to gender identity and the implications of reconstructive decisions. Long-term sequelae of cloacal exstrophy, including functional continence and sexual dysfunction, are recognized, and many patients require ongoing complex care into adulthood.

Understanding and managing a case of the omphalocele-exstrophy-imperforate anus-spinal defect complex.

The omphalocele-exstrophy-imperforate anus-spinal defects (OEIS) complex is a rare birth disorder involving a combination of gastrointestinal, musculoskeletal, renal, neural, and genitourinary system defects. We present a case report of a neonate with OEIS born by vertex spontaneous delivery to non-consanguineous parents. The major presenting defect was exstrophy of the cecum lying between two exstrophied halves of the bladder, an imperforate anus and spina bifida myelomeningocele. Explorative laparotomy revealed a duplex kidney system, attachment of the terminal ileum and cecum to the exstrophy, and a sausage-like atretic large bowel. Malrotation was also noted. Ladd's bands were released followed by ileostomy and ureterostomy. Patient was stable post-operatively and in the incubator on room air. OEIS remains a challenging anomaly that requires optimal treatment to facilitate the quality of life. With appropriate surgical intervention, the functional and social treatment goals for this unusual congenital defect can be met.

LUMBAR syndrome-OEIS complex overlap: A case series and review.

We present three new and six published infants with overlapping features of LUMBAR syndrome (lower body hemangioma, urogenital anomalies, spinal cord malformations, bony deformities, anorectal/arterial anomalies and renal anomalies) and OEIS complex (omphalocele, exstrophy, imperforate anus, and spinal defects), also known as cloacal exstrophy. OEIS is included under the recently proposed umbrella coined recurrent constellations of embryonic malformations (RCEMs). The RCEMs represent a phenotypically overlapping spectrum of rare disorders of caudal dysgenesis with unknown cause but likely shared pathogenesis. It has recently been proposed that LUMBAR be considered an RCEM. This report of infants with combined features of OEIS and LUMBAR is the first to demonstrate an overlap between LUMBAR and another RCEM, which supports LUMBAR's inclusion within the RCEM spectrum.

Clear as Mud: Readability Scores in Cloacal Exstrophy Literature and Its Treatment.

Purpose: This study examines the readability of online medical information regarding cloacal exstrophy (CE). We hypothesize that inappropriate levels of comprehension are required in these resources, leading to poor understanding and confusion amongst caregivers. Methods: The Google and Bing search engines were used to search the terms "cloacal exstrophy" and "cloacal exstrophy treatment". The first 100 results for each were collected. Each webpage was analyzed for readability using four independent validated scoring systems: the Gunning-Fog index (GFI), SMOG grade (Simple Measure of Gobbledygook), Dale-Chall index (DCI), and the Flesch-Kincaid grade (FKG). Results: Forty-seven unique webpages fit the inclusion criteria. Mean readability scores across all websites were GFI, 14.6; SMOG score, 10.8; DCI, 9.3; and FKG, 11.8, correlating to adjusted grade levels of college sophomore, 11th grade, college, and 11th grade, respectively. There were significant differences across all readability formulas. Non-profit websites were significantly less readable than institutional and commercial webpages (GFI p = 0.012, SMOG p = 0.018, DCI p = 0.021, FKG p = 0.0093). Conclusion: Caregiver-directed health information regarding CE and its treatment available online is written at the 11th grade reading level or above. Online resources pertaining to CE must be simplified to be effective.

A case report of single umbilical artery combined with fetal bladder exstrophy in singleton pregnancy and related literature review.

BACKGROUND: According to prenatal ultrasonographic studies, single umbilical artery may be present alone or in association with other fetal abnormalities. So far, the exact pathogenesis of bladder exstrophy is unclear. Some scholars believe that bladder exstrophy and cloacal exstrophy should be regarded as a disease spectrum to explore their pathogenesis. If bladder exstrophy and cloacal exstrophy are regarded as the same disease spectrum, then we can speculate that the single umbilical artery should have the probability of being accompanied by bladder exstrophy at the same time. CASE PRESENTATION: For the first time, we report a rare case of fetal bladder exstrophy with single umbilical artery in single pregnancy. This patient underwent targeted color Doppler ultrasound at 26 weeks of pregnancy which first suspected bladder exstrophy with single umbilical artery and fetal MRI for diagnosis at 38 + 3 weeks of pregnancy which confirmed the suspicion. After the diagnosis was confirmed, the patient was scheduled for a multidisciplinary discussion. Ultimately the patient opted for induced fetal demise at 38 + 5 weeks of pregnancy and the physical appearance of the fetal demise affirmed previous ultrasound and MRI examination results. CONCLUSIONS: Our report is the first finding of single umbilical artery combined with bladder exstrophy in a singleton pregnancy. Accordingly, our case enhances the evidence that cloacal exstrophy and bladder exstrophy should be treated as the same disease spectrum. In addition, we conducted a literature review on the diagnostic progress of single umbilical artery combined with bladder exstrophy, hoping to provide useful references for the diagnosis of this disease.

Ensuring our exstrophy-epispadias complex patients and families thrive.

Individuals with bladder exstrophy-epispadias complex (EEC) need long-term integrated medical/surgical and psychosocial care. These individuals are at risk for medical and surgical complications and experience social and psychological obstacles related to their genitourinary anomaly. This care needs to be accessible, comprehensive, and coordinated. Multiple surgical interventions, reoccurring hospitalizations, urinary and fecal incontinence, extensive treatment regimens for continent diversions, genital differences, and sexual health implications affect the quality of life for the EEC patient. Interventions must include psychosocial support, medical literacy initiatives, behavioral health services, school and educational consultation, peer-to-peer opportunities, referrals to disease-specific camps, mitigation of adverse childhood events (ACEs), formal transition of care to adult providers, family and teen advisory opportunities, and clinical care coordination. The priority of long-term kidney health will necessitate strong collaboration among urology and nephrology teams. Given the rarity of these conditions, multi-center and global efforts are paramount in the trajectory of improving care for the EEC population. To achieve the highest standards of care and ensure that individuals with EEC can thrive in their environment, multidisciplinary and integrated medical/surgical and psychosocial services are imperative.

Long-Term Management of Problems in Cloacal Exstrophy: A Single-Institution Review.

INTRODUCTION: Cloacal exstrophy (CE) is the most severe malformation of the exstrophy-epispadias complex. This study aims to discuss long-term sequela in a single major institution with a high volume of CE patients. MATERIALS AND METHODS: A prospectively maintained database of 1490 patients on the exstrophy epispadias spectrum (145 cloacal exstrophy) from 1974 to 2023. The patient database was reviewed for CE patients >10 years of age for genitourinary, gastrointestinal, orthopedic, and psychosocial outcomes. RESULTS: A total of 63 patients (43.4%) with ≥10 years of follow up were included for analysis. Thirty-nine (61.9%) patients were 18 years or older. Twenty-two (34.9%) patients were female and 39 (61.9%) male, 14 of whom were gender converted at birth. Two female patients conceived naturally and delivered via cesarean section. No male born CE patients had biological children. Catheterizable channels were common (45/63, 71.4%) and most (88.9%) were continent. Gastrointestinal diversion was managed mostly by colostomy (37/63, 58.7%). Three out of five (60.0%) patients who underwent PSARP were continent of stool. Twenty-two (34.9%) patients were wheelchair-bound. Psychosocial diagnoses included 52.4% (33/63) patients with anxiety/depression and 27.0% with chronic pain. Out of 56 patients evaluated by physical therapy, 75% were independent in ADL performance. Of patients older than 18, 79.5% (31/39) had attended college and 82.1% (32/39) were gainfully employed. CONCLUSION: Advances in critical care, nutrition, gastrointestinal, orthopedic, and urologic management have resulted in survival rates approaching 100% among patients with CE. While these children face long-term sequela spanning various organ systems, many lead independent and fully-functional lives. TYPE OF STUDY: Prognosis Study. LEVEL OF EVIDENCE: Level IV.

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.

Unrepaired cloacal exstrophy in an adult: Medical and ethical considerations.

Cloacal exstrophy, also known as OEIS complex, is a rare condition, comprised of severe congenital anomalies. This case report describes a 24-year-old 46,XY individual who had repair of the omphalocele at birth, but has remained with an unrepaired bladder exstrophy. This case highlights the intersections between medical decision-making, individualized management of complex patients, and ethical considerations for adults lacking capacity.

Multi-staged vs Single-staged Pelvic Osteotomy in the Modern Treatment of Cloacal Exstrophy: Bridging the Gap.

PURPOSE: Staged pelvic osteotomy has been shown in the past to be an effective tool in the closure of the extreme pubic diastasis of cloacal exstrophy. The authors sought to compare orthopedic complications between non-staged pelvic osteotomies and staged pelvic osteotomies in cloacal exstrophy. METHODS: A prospectively maintained exstrophy-epispadias complex database of 1510 patients was reviewed for cloacal exstrophy bladder closure events performed with osteotomy at the authors' institution. Bladder closure failure was defined as any fascial dehiscence, bladder prolapse, or vesicocutaneous fistula within one year of closure. There was a total of 172 cloacal exstrophy and cloacal exstrophy variant patients within the database and only closures at the authors' institution were included. RESULTS: 64 closure events fitting the inclusion criteria were identified in 61 unique patients. Staged osteotomy was performed in 42 closure events and non-staged in 22 closures. Complications occurred in 46/64 closure events, with 16 grade III/IV complications. There were no associations between staged osteotomy and overall complication or grade III/IV complications (p = 0.6344 and p = 0.1286, respectively). Of the 46 total complications, 12 were orthopedic complications with 6 complications being grade III/IV. Staged osteotomy closure events experienced 10/42 orthopedic complications while non-staged osteotomy closures experienced 2/22 orthopedic complications, however this did not reach significance (p = 0.1519). Of the 64 closure events, 57 resulted in successful closure with 6 failures and one closure with planned cystectomy. CONCLUSION: This study confirms, in a larger series, superior outcomes when using staged pelvic osteotomy in cloacal exstrophy bladder closure. Staged osteotomy was shown to be a safe alternative to non-staged osteotomy that can decrease the risk of closure failure in this group. Staged pelvic osteotomy should be considered in all patients undergoing cloacal exstrophy bladder closure. TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE: Level III.

Urological outcome with the use of salvage continent vesicostomy in pediatric reconstructive surgery. A single tertiary center experience.

PURPOSE: To report our experience and results in terms of complications, reoperation rate and urinary continence with the Salvage Continent Vesicostomy (SCV) technique in pediatric patients with history or need of enterocystoplasty and absent appendix. METHODS: Retrospective review of all patients with a history of a continent catheterizable channel surgery performed in our institution between June 2016 and January 2022. Only patients with a SCV surgery with a minimum 6-month post operative follow up were included in this cohort and divided in group 1 (history of previous bladder augmentation) and group 2 (simultaneous bladder augmentation and SCV). Primary outcome of the study was to assess both continence and postoperative complication rates. Early complications were assessed using the Clavien-Dindo classification (I-V). Late complications were focused on the need of further subfascial revision. RESULTS: 84 patients with a history of a continent stoma creation surgery were identified. In 20 of them (12 males) a SCV was performed. The mean age at surgery was 10.38 (range 4.87-15.6) years and the median postoperative follow-up time was 32 (range 6-64) months. Eleven patients were included in Group 1, while 9 patients in Group 2. Early complications occurred in 4 patients (20%), two of them required a re-intervention (Clavien-Dindo IIIb). Stoma subfascial revision was further required in 2 patient (10%). Continence rate at last follow up was 95%. CONCLUSIONS: In our early experience, the salvage continent vesicostomy has proven to be a simple continent stoma technique with acceptable both continence and complication rates that can be used in selected patients with a history or need of bladder augmentation and absent appendix.

Case report: Duplicated appendicitis with history of cloacal exstrophy causing bowel obstruction.

INTRODUCTION: Cloacal and bladder exstrophy are rare embryological defects that can cause developmental disruption of surrounding organ structures, the pelvis, spinal cord, and small intestines being the most commonly affected. Duplicated appendix is another rare embryological defect that has historically caused confusing clinical presentations. Our case highlights a rare instance of a patient with cloacal exstrophy who presented with a bowel obstruction and an associated inflamed duplicated appendix. CASE PRESENTATION: A newborn male is born with omphalocele-exstrophy-imperforate anus-spinal defects (OEIS) complex. As primary surgical reconstruction was pursued, the patient was found to have a non-inflamed duplicated appendix, which was left unremoved. In the following months, the patient experienced episodes of small bowel obstruction, eventually requiring surgical intervention. During this operation, the duplicated appendix was noted to be inflamed, prompting removal of both appendices. DISCUSSION: This case highlights the increased prevalence of duplicated appendix in a patient with cloacal exstrophy, as well as the utility of prophylactic appendectomy for patients incidentally found to have a duplicated appendix intraoperatively. The duplicated appendix may lead to increased rates of complications and atypical presentation of appendicitis, supporting the practice of prophylactic appendectomy in patients with an incidentally found duplicated appendix. CONCLUSION: We suggest clinicians be aware of the association and potentially atypical presentation of appendicitis in patients with a duplicated appendix, particularly in the setting of cloacal exstrophy. The decision to prophylactically remove an incidentally found, non-inflamed duplicated appendix may be beneficial in preventing confusing clinical presentations and future complications.

The clinical features of patients who underwent bladder augmentation of cloacal exstrophy and their functional outcomes: the results of a nationwide survey in Japan.

PURPOSE: Cloacal exstrophy (CE) patients may need bladder reconstruction after initially undergoing surgery to obtain continence and improve their quality of life. This study attempts to clarify the clinical features of CE patients who underwent bladder augmentation (BA) and their urinary functional outcomes based on a nationwide survey in Japan. METHODS: A questionnaire survey was conducted, and 150 CE patients were enrolled. Their clinical characteristics and urinary outcomes were reviewed. RESULTS: BA was performed in 52 patients (34.7%). Most cases underwent early bladder closure at initial surgery in neonate period. The age at the BA was performed 6.4 [6-9.0] years. Among them, the most used organ for BA was ileum (n = 30, 57.7%). Regarding the outcomes, the age when the renal function was evaluated was 14.0 [10.0-20.5] years and the serum creatinine level was 0.44 [0.36-0.60] (mg/dl). Clean intermittent catheterization was required in 37 (71.2%) patients. On the other hand, no dialysis or kidney transplantation was necessary in any of these patients. CONCLUSION: The renal function and conditions of patients who underwent BA were relatively well preserved. Individualized management with a stepwise surgical approach for CE patients should thus be considered in the future.

Exome Survey and Candidate Gene Re-Sequencing Identifies Novel Exstrophy Candidate Genes and Implicates LZTR1 in Disease Formation.

BACKGROUND: The bladder exstrophy-epispadias complex (BEEC) is a spectrum of congenital abnormalities that involves the abdominal wall, the bony pelvis, the urinary tract, the external genitalia, and, in severe cases, the gastrointestinal tract as well. METHODS: Herein, we performed an exome analysis of case-parent trios with cloacal exstrophy (CE), the most severe form of the BEEC. Furthermore, we surveyed the exome of a sib-pair presenting with classic bladder exstrophy (CBE) and epispadias (E) only. Moreover, we performed large-scale re-sequencing of CBE individuals for novel candidate genes that were derived from the current exome analysis, as well as for previously reported candidate genes within the CBE phenocritical region, 22q11.2. RESULTS: The exome survey in the CE case-parent trios identified two candidate genes harboring de novo variants (NR1H2, GKAP1), four candidate genes with autosomal-recessive biallelic variants (AKR1B10, CLSTN3, NDST4, PLEKHB1) and one candidate gene with suggestive uniparental disomy (SVEP1). However, re-sequencing did not identify any additional variant carriers in these candidate genes. Analysis of the affected sib-pair revealed no candidate gene. Re-sequencing of the genes within the 22q11.2 CBE phenocritical region identified two highly conserved frameshift variants that led to early termination in two independent CBE males, in LZTR1 (c.978_985del, p.Ser327fster6) and in SLC7A4 (c.1087delC, p.Arg363fster68). CONCLUSIONS: According to previous studies, our study further implicates LZTR1 in CBE formation. Exome analysis-derived candidate genes from CE individuals may not represent a frequent indicator for other BEEC phenotypes and warrant molecular analysis before their involvement in disease formation can be assumed.