Modified partial penile disassembly repair for improved functional and cosmetic outcome in isolated male epispadias.

INTRODUCTION AND OBJECTIVE: The objective of the study was to evaluate the functional and cosmetic outcome of single-stage modified partial penile disassembly repair in isolated male epispadias. MATERIALS AND METHODS: A retrospective analysis of 15 cases of primary epispadias repair, from June 2015 to December 2018, was performed. Patients were classified by the type of epispadias, urinary incontinence, chordee, and rotation. SURGICAL TECHNIQUE: Penile degloving with the mobilization of the urethral plate from the ventral to the dorsal aspect with the preservation of blood supply at both ends, distally up to the level of mid-glans and proximally up to the pubic symphysis is done. Tubularization of urethral plate followed by spongioplasty, corporoplasty with medial rotation of corporeal bodies, and glanuloplasty with meatoplasty was done to bring the meatus ventrally. The skin cover is done by the rotation of the ventral flaps and the z-plasty whenever required. RESULTS: Age of the patients varied from 4 months to 21 years with a mean of 11 years. Thirteen patients had excellent cosmetic outcome while two patients had minimal residual chordee but did not require any surgery in a follow-up. Five patients with partial incontinence in the study group achieved continence after surgery. None of the patients developed complications such as fistula or stricture. All five male patients in the post-pubertal group reported normal erections and successful ejaculations after the surgery. Follow-up ranged from 3 months to 18 months. CONCLUSIONS: Modified partial penile disassembly incorporates all the benefits of Cantwell Ransley repair and needs less extensive dissection than total penile disassembly. Both functional and cosmetic results are good with a low complication rate.

Long-term Kidney Outcomes in Exstrophy-Epispadias Complex: How Patients Present as Adults.

OBJECTIVE: To characterize kidney function in patients with exstrophy-epispadias complex (EEC) at time of presentation for adult urologic care. MATERIALS AND METHODS: This was a retrospective analysis of 23 patients (ages 18-57) with EEC who presented to a single tertiary care center from 2001-2020. Kidney function was evaluated based on calculated eGFR and presence of hydronephrosis on imaging. UDS data was used to evaluate the bladder. RESULTS: Patients had undergone a variety of different surgical techniques for exstrophy or epispadias repair prior to presentation to an adult urologist. We found that 10 of the 23 patients had evidence of CKD Stage II or higher at the time of presentation and 7 patients had evidence of hydronephrosis on imaging. There was urodynamics data available for 14 patients, of which 8 patients showed poor (≤15 ml/cmH2O) or intermediate (15-20 ml/cmH2O) bladder compliance. CONCLUSION: In conclusion, some patients with EEC have evidence of kidney dysfunction at time of presentation to an adult urologist. It is important to consider this when caring for patients with EEC as adults.

Development of Late Continence in Bladder Exstrophy and Epispadias Patients.

OBJECTIVE: To evaluate to what extend urinary continence develops during puberty in patients with classic bladder exstrophy (CBE) and epispadias. METHODS: The operative database was reviewed for surgical procedures and urinary continence in all 65 CBE and epispadias patients born in 1976-2005. Excluded were 2 patients who had insufficient data for evaluation. RESULTS: Thirty-five patients with volitional voiding were incontinent at the age of 10 years, 27 had daily incontinence, and 8 had rare incontinence. Sixteen patients (46%) became later fully continent without any major surgery (except Deflux injections in 3 patients) or CIC treatment. Among these 16 fully continent patients there were 7/8 with rare incontinence, 9/23 with daily incontinence (P = .04); 3/9 males with CBE, 10/13 males with epispadias, 3/5 females with CBE, and 0/4 females with epispadias (P = .25 between sex and P = .48 between diagnosis). Of the 15 patients remaining incontinent, 10 had daily and 5 had rare incontinence episodes. The latest control was at the median age of 19 years (interquartile range 17-21 years). Twenty-five patients (40% of the whole material) were fully continent (11/38 (29%) with CBE and 14/25 (56%) with epispadias, P = .04) and 8 (13%) had rare incontinence with volitional voiding (1/38 [3%] with CBE and 7/25 [28%] with epispadias). CONCLUSION: Almost half of the incontinent CBE and epispadias patients with volitional voiding achieved continence after the age of 10 without major surgery. Prognosis for pubertal development of continence was best in patients with rare incontinence and in males with epispadias.

Further support linking the 22q11.2 microduplication to an increased risk of bladder exstrophy and highlighting LZTR1 as a candidate gene.

BACKGROUND: The bladder exstrophy-epispadias complex (BEEC) is a congenital malformation of the bladder and urethra. The underlying causes of this malformation are still largely unknown; however, aside from environment, genetics is thought to play an essential role. The recurrent 22q11.2 microduplication is the most persistently detected genetic aberration found in BEEC cases. METHODS: We performed array comparative genomic hybridization (array-CGH) analysis of 76 Swedish BEEC patients. Statistical analysis was performed on current dataset pooled with previously published data on the 22q11.2 microduplication in BEEC patients. We performed massive parallel sequencing (MPS) of the 22q11.2 region in 20 BEEC patients without the 22q11.2 microduplication followed by functional studies. RESULTS: We identified three additional cases with the 22q11.2 microduplication. Pooling data from this study with previously published reports showed a statistically significant enrichment of the 22q11.2 microduplication in BEEC patients (2.61% in cases vs. 0.08% in controls; OR = 32.6; p = 8.7 × 10-4 ). MPS of the 22q11.2 region in 20 BEEC patients without the 22q11.2 microduplication identified a novel variant in LZTR1 (p.Ser698Phe) in one patient. Functional evaluation of the LZTR1 p.Ser698Phe variant in live NIH 3T3 cells showed that the concentration and cytoplasmic mobility differ between the Lztr1wt and Lztr1mut , indicating a potential functional effect of the LZTR1mut . CONCLUSION: Our study further emphasizes the involvement of the 22q11.2 region in BEEC development and highlights LZTR1 as a candidate gene underlying the urogenital malformation.

Cystectomy in the Pediatric Exstrophy Population: Indications and Outcomes.

OBJECTIVE: To explore the long-term outcomes and indications for cystectomy in patients with bladder exstrophy. Although rare, cystectomy is the final surgical alternative to bladder repair among these patients with a poor quality bladder template. METHODS: A prospectively maintained database of 1298 patients with exstrophy-epispadias complex was reviewed for patients who underwent cystectomy between 1970 and 2015 at the authors' institution. Demographic data, indication for cystectomy, surgical history, postoperative outcomes, and continence status were collected. RESULTS: Eighteen (6 male; 12 female) patients with exstrophy (15 classic bladder exstrophy; 2 bladder exstrophy variants; 1 cloacal exstrophy) underwent cystectomy at a median age of 3.8 years. Six patients (33.3%) underwent primary cystectomy without attempted bladder closure. Eight patients (44.4%) had a history of failed primary closure with loss of capacity or inadequate growth after closure. Four patients (22.2%) had successful primary closure but underwent cystectomy secondary to poor bladder compliance with declining renal function or poor bladder growth or quality. Urinary diversion included 6 cutaneous ureterostomies, 4 bowel conduits (1 ileal; 3 colon), 6 continent urinary diversions with ileosigmoid reservoir, and 1 ureterosigmoidostomy. Of 8 patients who underwent a continence procedure, all were dry at a median of 25.3 months after cystectomy. CONCLUSION: Cystectomy was most commonly indicated in intrinsically diseased bladder templates that remained too small despite permitting time for interval growth. These bladders often were of poor quality and compliance and did not reduce into the pelvis on examination. It was, however, possible to achieve urinary continence in these patients with cystectomy and urinary diversion.

Sexual Function and Quality of Life in Adult Male Individuals with Exstrophy-Epispadias Complex-a Survey of the German CURE-Network.

OBJECTIVE: To investigate sexual function and quality of life (QoL) in adult male individuals with exstrophy-epispadias complex (EEC). Data from the German Network for Congenital Urorectal Malformations (CURE-Net) were used. PATIENTS AND METHODS: Fifty-one male participants (≥18 years) recruited by CURE-Net between 2009 and 2012 were re-contacted per mail and asked to fill out 4 questionnaires including International Index of Erectile Function (IIEF-5), Cologne Assessment of Erectile Dysfunction (KEED), the Short-Form 36 (SF-36), and one self-designed questionnaire about their medical history, current health status, and sexual experience. The SF-36 results were compared with general German population. RESULTS: Nineteen male participants (37%) completed all questionnaires (median age 26 years, 84% classical bladder exstrophy). The majority (68%) was reconstructed in a staged or single-staged approach; further 32% had a primary urinary diversion. Seventy-four percent of the participants reported a certain degree of urinary incontinence. Mean IIEF-15 results showed mild to moderate or moderate impairment in all domains. The SF-36 results revealed no difference in the German population. Subgroup analysis showed statistically significant lower results in certain SF-36 domains with regard to incontinence, dissatisfaction with genital appearance, and antihypertensive drug intake. CONCLUSION: Although there is no difference in overall QoL comparing male individuals with EEC to the general German population, incontinence, dissatisfaction with genital appearance, and taking antihypertensive medication seem to have a considerable impact on QoL. Furthermore, mild to moderate erectile dysfunction and moderate intercourse satisfaction were confirmed, suggesting the need for further improvement in care for adult male individuals with EEC.

Comparing the bulking effect of calcium hydroxyapatite and Deflux injection into the bladder neck for improvement of urinary incontinence in bladder exstrophy-epispadias complex.

OBJECTIVES: The aim of this study was to evaluate the efficacy of the endoscopic injection of calcium hydroxyapatite (CaHA) into the bladder neck (BN) region of patients with urinary incontinence and bladder exstrophy-epispadias complex (BEEC). PATIENTS AND METHODS: We designed a retrospective cohort study in which we retrospectively studied medical charts of female and male patients of BEEC who had undergone CaHA or Deflux injection for continence improvement between 2009 and 2014. Sixteen incontinent patients with a mean ± SD age of 8.09 ± 3.5 years received an endoscopic submucosal injection of 5.4 ml of pure CaHA powder with autologous plasma (group A). Patients in group B (N = 21), control group, with a mean ± SD age of 7.51 ± 2.8 years received Deflux injection (5.1 ml). The mean follow-up after injection was 38 ± 5.2 and 33 ± 4.1 months in groups A and B, respectively. RESULTS: No post-injection complication was detected in none of the patients during the follow-up. Eleven patients (68.75%) in group A became socially dry following 1-2 injections, the degree of incontinence was improved in 4 patients (25%), and there was no change in one patient (6.25%). However, Deflux injection resulted in complete dryness in 14 (66.66%), improvement in the degree of incontinence in 5 (23.81%) and no change in 2 patients (9.52%), leading to no significant difference in continence achievement between CaHA and Deflux groups (p = 0.9). The statistical analysis was not significantly different in terms of bladder capacity (p = 0.7) or Q max (p = 0.8). CONCLUSION: The preliminary results of this study revealed that CaHA may be applied as an affordable bulking agent in treatment of urinary incontinence in BEEC.

Epispadias and the associated embryopathies: genetic and developmental basis.

The abnormalities in the urogenital organs are frequently observed as human developmental diseases. Among such diseases, the defects in the upper part of external genitalia are rather rare named epispadias. The cleft in the dorsal part of external genitalia often reaches to the urethra. In general, the urogenital abnormalities accompany defects in the adjacent tissues and organs. The ventral body wall and bladder can also be affected in the patients with dorsal defects of the external genitalia. Therefore, such multiple malformations are often classified as bladder exstrophy and epispadias complex (BEEC). Because of the lower frequency of such birth defects and their early embryonic development, animal models are required to analyze the pathogenic mechanisms and the functions of responsible genes. Mutant mouse analyses on various signal cascades for external genitalia and body wall development are increasingly performed. The genetic interactions between growth factors such as bone morphogenetic proteins (Bmp) and transcription factors such as Msx1/2 and Isl1 have been suggested to play roles for such organogenesis. The significance of epithelial-mesenchymal interaction (EMI) is suggested during development. In this review, we describe on such local interactions and developmental regulators. We also introduce some mutant mouse models displaying external genitalia-body wall abnormalities.

Is 1p36 deletion associated with anterior body wall defects?

Epispadias and exstrophy of the cloaca, also known as OEIS complex (omphalocele, exstrophy, imperforate anus, spinal defects), respectively constitute the most benign and severe ends of the bladder exstrophy-epispadias complex (BEEC) spectrum. In 2009, El-Hattab et al. reported the first patient with OEIS complex associated with a chromosome 1p36 deletion. Here we report a second patient with 1p36 deletion who also has classic bladder exstrophy, supporting the possible role of genes in this region in the development of BEEC. The absence of omphalocele and imperforate anus in our patient places him toward classic bladder exstrophy while presence of spina bifida and the absence of coccyx suggest an overlap with OEIS complex. An additional differential diagnosis is the pentalogy of Cantrell in our patient as he also has a diaphragmatic hernia and an incomplete sternum. This is the second observation of a ventral midline birth defect in association with 1p36 deletion syndrome, following El-Hattab et al.'s report [2009]. The three genes (NOCL2, DVL1, and MMP23B) discussed as possible candidates are also among the deleted ones in our patient, supporting the possible role of these genes in BEEC spectrum. © 2016 Wiley Periodicals, Inc.

Psychosocial screening at paediatric BEEC clinics: a pilot evaluation study.

INTRODUCTION: Bladder Exstrophy and Epispadias Complex (BEEC) is associated with an increased risk of impaired mental health, quality of life, and psychosocial functioning. Therefore, screening patients to help identify and evaluate potential psychosocial difficulty is arguably an important consideration for BEEC Services. OBJECTIVE: To screen paediatric BEEC patients for a range of general psychosocial difficulties in a multi-disciplinary out-patient clinic setting. STUDY DESIGN: This cross-sectional evaluation was conducted between April 2012 and July 2013. Families attending BEEC multi-disciplinary out-patient clinics were asked to complete a range of standardised psychosocial questionnaires, including the Paediatric Quality of Life Inventory (PedsQL 4.0 Generic Core and Family Impact Module), the Strengths and Difficulties Questionnaire (SDQ), the Paediatric Index of Emotional Distress (PI-ED), and the Hospital Anxiety and Depression Scale (HADS). 108 children attended clinic of which 80 (74.1%) patients and their parents/carers completed some or all of the questionnaires. The mean patient age was 8.41 years (SD = 4.46, range = 1-18 years). There were more boys (N = 50, 62.5%) and the majority had a diagnosis of classic bladder exstrophy (N = 51, 63.8%), followed by primary epispadias (N = 22, 27.5%) and cloacal exstrophy (N = 7, 8.7%). RESULTS: Mean total scores fell within the average/normal range on all questionnaires used (See table below). However, variation around these means was high. Age, gender and diagnosis were found to significantly influence certain questionnaire responses with older-age groups, males, and those with classic bladder exstrophy particularly at risk across some domains. The children/adolescents self-reported better health related quality of life (HRQoL) scores than published results for a range of paediatric chronic health conditions. Differences between parent and child responses on both the PedsQL and SDQ favoured a more positive response on the child self-report questionnaire but were not statistically significant. DISCUSSION: Mean scores on the measures used suggest a relatively optimistic picture of general psychosocial well-being, especially for HRQoL, in the BEEC population studied. Positive HRQoL outcomes have recently been reported for BEEC paediatric populations. Our results reflect this trend with better mean HRQoL scores than paediatric patients with a range of other chronic health conditions. However, this optimism is cautious given the limitations of this evaluation study and the high variation around the means. Limitations included the small sample size (especially for patients with cloacal exstrophy), the lack of a control group, the limited sensitivity of generic questionnaires in respect of BEEC-specific issues, and the low mean age of patients in the study. Future screening programmes may wish to consider measuring BEEC-specific variables (e.g. satisfaction with genital appearance/function); collecting information on medical aspects, such as continence, pubertal stage and frequency/timing of medical intervention; and asking both parents/carers (where possible) to complete the questionnaires. CONCLUSIONS: Screening questionnaire responses were used in conjunction with clinical psychology consultations to evaluate a range of psychosocial aspects in BEEC paediatric patients. Whilst mean scores on the measures used suggest a relatively optimistic picture, certain individual scores did fall within the clinical ranges, highlighting the potential need for further assessment. Developmentally tailored consultations with a clinical psychologist can provide detailed information around questionnaire responses and further assess BEEC specific aspects.

Aesthetic, urological, orthopaedic and functional outcomes in complex bladder exstrophy-epispadias's management.

BACKGROUND: Postoperative complications are related to the surgical procedures, of failures of initial bladder closure and influence the urological, aesthetical and orthopaedic outcomes. MATERIALS AND METHODS: We reviewed four patients who underwent complex bladder exstrophy-epispadias repair over a period of 14 years. The outcomes of treatment were assessed using, aesthetic, urological and orthopaedic examination data. Orthopaedic complications were explored by a radiography of the pelvis. RESULTS: Out of four patients who underwent bladder exstrophy surgical management, aesthetic, functional outcomes and complications in the short and long follow-up were achieved in three patients. The first patient is a male and had a good penis aspect. He has a normal erection during micturition with a good jet miction. He has a moderate urinary incontinence, which requires diaper. In the erection, his penis-measures 4 cm long and 3 cm as circumference. The second patient was a female. She had an unsightly appearance of the female external genitalia with bipartite clitoris. Urinary continence could not be assessed; she did not have the age of cleanness yet. The third patient had a significant urinary leakage due to the failure of the epispadias repair. He has a limp, a pelvic obliquity, varus and internal rotation of the femoral head. He has an inequality of limbs length. Pelvis radiograph shows the right osteotomy through the ilium bone, the left osteotomy through the hip joint at the acetabular roof. CONCLUSION: When, the epispadias repair is performed contemporary to initial bladder closure, its success is decisive for urinary continence. In the female, surgical revision is required after the initial bladder closure for an aesthetic appearance to the external genitalia. Innominate osteotomy must be performed with brilliancy amplifier to avoid osteotomy through to the hip joint to prevent inequality in leg length.

The fate of the complete female epispadias and exstrophy bladder--is there a difference?

PURPOSE: Complete female epispadias, which occurs much more rarely than classic bladder exstrophy in females, is thought to have a more benign clinical course. We hypothesized that patients with complete female epispadias are more likely to have a larger bladder capacity and achieve voiding continence than females with classic bladder exstrophy. MATERIALS AND METHODS: After obtaining institutional review board approval, females with complete female epispadias or classic bladder exstrophy were identified from an institutionally approved prospective database. We retrospectively reviewed the charts of 22 patients with complete female epispadias and 23 with female classic bladder exstrophy, including 3 with delayed primary closure. RESULTS: Patients with complete female epispadias presented later and underwent the first reconstructive procedure at an older age than patients with classic bladder exstrophy. Patients with complete female epispadias had lower initial and final age adjusted bladder capacity than those with classic bladder exstrophy but the bladder growth rate did not differ between the groups. When patients with complete female epispadias were stratified by age at initial reconstruction, there was no difference in final age adjusted bladder capacity or the bladder growth rate. There was also no statistical difference between the groups in the number of surgeries, continence rate from initial reconstruction, bladder neck reconstruction success or need for a continent stoma. CONCLUSIONS: This study suggests that females with classic bladder exstrophy who undergo successful primary closure have higher initial and final age adjusted bladder capacity than females with complete female epispadias but with a similar growth rate. This may reflect the creation of outlet resistance at a younger age than in those with complete female epispadias. However, no difference was identified between patients with complete female epispadias who initially underwent repair before vs after age 1 year. Patients with complete female epispadias undergo procedures to achieve continence that are similar to those in patients with classic bladder exstrophy.

Epispadias repair: functional outcome of complete disassembly.

PURPOSE OF REVIEW: Complete penile disassembly (CPD) is a widely utilized procedure for epispadias repair. The rarity of the anomaly and limited number of patients in published series limit our ability to fully evaluate the outcome of such a technique. RECENT FINDINGS: We reviewed the literature for published data on CPD. We looked at different complications of the procedure and the main modifications to alleviate such complications. We looked at functional data on the effect of such a technique on erectile function. This review should be helpful in parents/patient counseling. Future areas for research are suggested. SUMMARY: CPD is a safe and highly successful technique for epispadias repair in infants, boys and adults. There is an ongoing concern with the procedure in neonates. The procedure has a satisfactory outcome when performed for isolated epispadias. In the exstrophy population, long-term data are required to evaluate the outcome of the technique on urinary continence and sexual functions.

Female epispadias managed by bladder neck plication via a perineal approach.

Female epispadias is a rare genitourinary anomaly characterized by urinary incontinence and typical appearance of the external genitalia. Traditional surgical approaches have involved a staged genitoplasty and interval bladder neck reconstruction. We describe further experience of a promising single-stage technique using a cystoscopically guided bladder neck plication via a perineal approach with combined genitoplasty.

Health related quality of life in adolescents with abnormal bladder function: an assessment using the Child Health and Illness Profile-Adolescent Edition.

PURPOSE: We studied the impact of abnormal bladder function due to congenital urological disorders on health related quality of life in children. A reliable patient based method is needed to assess the impact of these conditions in children and the interventions used to treat them. MATERIALS AND METHODS: Participants 11 to 17 years old with bladder exstrophy-epispadias complex, spina bifida or other causes of abnormal bladder function self-administered the Child Health and Illness Profile-Adolescent Edition, a generic health related quality of life instrument. They also responded to questions about incontinence, catheterization status and bother level. Mean scores on the profile were compared to population based norms. RESULTS: Mean age of the 50 participants was 14.9 years, 62% were male and 82% were white. Diagnoses included bladder exstrophy-epispadias complex in 37 patients, spina bifida in 10 and other in 3. The mean +/- SD score on the disorders domain of 14.2 +/- 6.3 was significantly worse than the population norm of 20. Mean scores on the satisfaction, discomfort, resilience, risks and achievement domains were comparable to or better than the population based norm of 20. A total of 29 participants reported incontinence and 31 performed catheterization. CONCLUSIONS: In this study of adolescents with congenital causes of abnormal bladder function Child Health and Illness Profile-Adolescent Edition generic health related quality of life scores were significantly worse in the disorders domain but largely comparable to or better than those of the general population in other domains. This suggests that the profile may discern between adolescents with structural urological disease and norms but it may not be sensitive enough to fully detect the impact of the condition. Alternatively adolescents may adapt well to the challenges of urological disease.

The exstrophy-epispadias complex.

Patients with the exstrophy-epispadias complex are one of the most challenging groups encountered by pediatric urologists. They generally require surgery involving several reconstruction techniques, usually performed after the first week of life. Common problems in subsequent years include issues related to continence, sexual function, and the appearance of the lower abdomen and genitals. This article reviews major publications over the last few years related to managing patients with this rare, complex, congenital genitourinary anomaly.

New insight into surgical anatomy of epispadiac penis and its impact on repair.

PURPOSE: Surgical anatomy of the epispadiac penis is still not fully described. Using our complete disassembly technique, we discovered some anatomical features of epispadiac penis that may have significant impact on surgical outcome. MATERIALS AND METHODS: A total of 52 patients 2 days to 19 years old (mean age 43 months) underwent primary repair of epispadias between October 1996 and December 2006. After complete penile disassembly, ie full mobilization of the corporeal bodies, neurovascular bundles and urethral plate, reassembly of the penile entities was done. The urethral plate is tubularized and ventralized. The corporeal bodies are straightened and lengthened by 2 transverse incisions and grafting, joined medially and fixed to the glans cap. The glans is reconstructed, and the neurovascular bundles are moved dorsally and joined. The skin is reconstructed using different local flaps. RESULTS: Investigating the anatomical features of the epispadiac penis, we discovered several distinguishing features. The corporeal bodies are separated and triangular in shape. They represent the main substrate of dorsal curvature due to the significant disproportion in length between the long ventral and short wedge-shaped dorsal sides. The length of the neurovascular bundles is determined by their course-they are longer if they overlie the ventral side of the corpora and shorter if positioned over the dorsal side. The skin between the scrotum and penis has characteristics similar to penile skin. A good functional and esthetic outcome was achieved in 46 patients. Erection and glanular sensitivity were preserved in all patients. There was no necrosis of the glans or corporeal bodies. Complications included urethral fistula in 4 patients, stenosis in 2 and mild residual curvature in 2. CONCLUSIONS: New insights into the anatomical features of the epispadiac penis can have a significant impact on surgical outcomes.

Recent advances in external genitalia.

In the last decade, significant progress in the knowledge and management of external genital anomalies has been achieved, including an improved understanding of epidemiology and pathophysiology of these anomalies, the identification of etiologic genetic defects, and significant improvements in surgical approaches that have decreased complications and improved cosmetic outcomes. We highlight the most clinically important advances of the commonly encountered external genital anomalies.

The morphogenesis of the exstrophy-epispadias complex: a new concept based on observations made in early embryonic cases of cloacal exstrophy.

BACKGROUND: The term exstrophy-epispadias complex (EEC) has been coined for a group of congenital malformations that includes epispadias, bladder exstrophy and cloacal exstrophy. It is usually thought that these malformations develop against a similar embryological background. This background, however, is still obscure. This is mainly due to the lack of availability of abnormal human or non-human embryos showing the crucial developmental steps in the morphogenesis of EEC malformations. In this paper, we present chick embryos that show cloacal exstrophy at early developmental stages. To the best of our knowledge, this is the first documentation of this rare malformation in young embryos. MATERIALS AND METHODS: Embryos with cloacal exstrophy (n=4) were found among embryos from two experimental series (n=50) that were primarily performed to document the early morphogenesis of facial and cardiovascular malformations. The malformations were induced by the administration of suramin according to established protocols. Suramin can induce a spectrum of malformations including facial clefts, heart defects, and cloacal exstrophy. RESULTS AND CONCLUSIONS: Besides the presence of an abnormal opening into the cloaca, all embryos were characterised by an abnormal broadening of the caudal trunk at the level of the leg buds, which, in the youngest embryos, was associated with the abnormal presence of large aneurysmatic swellings of the dorsal aortae at this side. We postulate that these aneurysmatic swellings might be the primary defects leading to the development of EEC malformations. These space-occupying anomalies seem to cause abnormal distensions of the developing pelvis and of the infra-umbilical portion of the developing body wall. In consequence, the mid-portion of the developing ventral body wall between the origin of the umbilical cord and the cloacal plate becomes stretched and thinned out. Tension and thinning of the ventral body wall might ultimately lead to its rupture with exposure of the lumen of the embryonic cloaca and allantois. This new concept on the morphogenesis of the EEC is the first not to be inferred from the conditions seen in fetal or postnatal human cases but is based entirely on data from malformed embryos.