What Is Exstrophy Epispadias Complex - Features, Anomalies, Diagnosis, and Treatment

Introduction

The Exstrophy epispadias complex is a severe variety of abdominal midline malformations. The characteristics of the exstrophy epispadias complex include the urinary system, the pelvis, the pelvic floor, the musculoskeletal system, the genitalia, the abdominal wall, and sometimes the anus and the spine. In addition to these malformations, weakened abdominal muscles, a shorter-than-average urethra, and shortened external genitalia (vagina or penis) may also occur. The condition develops in utero when the abdominal wall and underlying organs fail to fuse properly, leaving the bladder inside out and exposed on the outside of the body. The exstrophy epispadias complex includes a spectrum with different severity levels, extending from epispadias (the mildest form, with upper and lower fissures) to bladder exstrophy and exstrophy of the cloaca. The latter is also referred to as omphalocele, exstrophy, imperforate anus, and spinal defects complex (OEIS) and is the most severe form. OEIS often involves several systems, including the urinary, reproductive, and intestinal tracts and musculoskeletal defects. Exstrophy epispadias complex is subdivided into ‘typical’ or ‘classic’ forms. The classic forms are epispadias, classical bladder exstrophy, and exstrophy of the cloaca, and atypical forms include duplicated exstrophy, covered exstrophy, and pseudo-exstrophy.

What Is the Clinical Description of Exstrophy Epispadias Complex?

• Classical Bladder Exstrophy: The evaginated bladder plate of different individual sizes characterizes classical bladder exstrophy. Urine may be observed dripping from the ureteric orifices on the bladder orifices. The visible bladder mucosa may be reddish at birth, and mucosal polyps are seen on the surface. Delayed closure leads to further mechanical or inflammatory alterations with signs of mucosal inflammation, including whitish coating, ulcerations, and hyperplastic formations. The normal skin and squamous metaplastic area are differentiated by paraexstrophy, shining, thick skin, which stripes the transition junction. Inferior to the umbilicus, rectus diastasis, and small umbilical hernias can be palpated. The pubic bones can be palpated on both sides of the bladder template. Weakness in the abdominal muscles and the failure of normal pelvic bone fusion are also common in bladder exstrophy, which can contribute to pelvic instability.
• Epispadias: Epispadias are caused due to developmental arrests caused by the urethral plate's nonclosure and the abnormal dorsal urethral location. Hence, in males, an ectopic meatus is located on the dorsal side of the penis, and in females, there is often a variable cleft in the urethra. In both boys and girls, epispadias can occur in isolation, where the bladder is fully developed and enclosed by the abdominal wall, but this is a rare occurrence.

Based on the location, epispadias is classified as:

In Boys:

• Penopubic.
• Penile.
• Glandular.

In Girls:

• Gaping meatus.
• Intermediate.
• Severe.

The symphysis is normal in both sexes; if the gap is present, it is minor. The minor gap may be palpable, which indicates only minor pelvic and pelvic floor anomalies. The main clinical symptom includes urinary incontinence due to the involvement of the urinary sphincter.

• Cloacal Exstrophy: It is one of the significant congenital disabilities and involves several vital organs. Other defects may include omphalocele, spinal defects, and imperforate anus, which require immediate surgery. Often, a foreshortened hindgut or cecum ends between the two atrophied hemibladders. Additionally, the symphysis pubis appears separated, with the pelvis exhibiting asymmetry, in contrast to the symmetrical shape typically seen in classical bladder exstrophy. The treatment for cloacal exstrophy is extremely complex as there are multiple organ systems involved, and reconstructive surgery often takes place over several stages.
• Exstrophy Variants: They include a clinically homogeneous spectrum. The exstrophy may mimic classical bladder exstrophy, and parts of the bladder mucosa may have a reddish appearance on the roof of the skin. An umbilicus may be present at an orthotopic place. Pseudo-exstrophy may be less likely to be seen during birth and at older ages. The individuals may not have obvious symptoms but may be found during investigations. Prenatal diagnosis through ultrasound or MRI allows for early planning of post-birth management.

What Are the Anomalies Associated With the Exstrophy Epispadias Complex?

• Urologic Anomalies: In both genders, urologic malformations such as ureteropelvic junction obstruction, ectopic pelvic kidney, horseshoe kidney, renal hypo- or agenesis, ureteral ectopy, and ureterocele are observed in one-third of all exstrophy epispadias complex cases. In addition, there is a 100 percent prevalence rate of bilateral vesicoureteral reflux due to the developmental failure of the ureterovesical junction. Urinary tract infections (UTIs) and chronic kidney disease (CKD) can develop in cases where vesicoureteral reflux is severe and untreated.
• Spinal and Orthopedic Abnormalities: In children, spinal abnormalities are seen in seven percent of the exstrophy epispadias complex cases. Other cases involve congenital spinal anomalies caused by improper closure of the neural tube early in life development and abnormal development of the caudal mass, confirmed by magnetic resonance imaging (MRI). Therefore, it is recommended that newborns with exstrophy of the cloaca are subjected to spinal ultrasound and radiography to detect abnormalities ranging from hemivertebra to myelomeningocele. Mainly, skeletal exstrophy of the cloaca and limb anomalies (absence of feet, clubfoot deformities, tibial or fibular deformities, and hip dislocations) are commonly detected. The affected individuals are recommended to undergo a sonographic examination.
• Gastrointestinal Anomalies: Gastrointestinal abnormalities are usually associated with exstrophy of the cloaca and are less likely to be present in classical bladder exstrophy or epispadias. Other findings include common hindgut remnants of varying size, omphaloceles, gastrointestinal malrotation, and short bowel syndrome in 46 percent of cases. Rarely, duodenal atresia and small bowel syndrome cause absorptive dysfunction. In some cases, surgical resection of affected bowel segments is necessary, and children may require nutritional support such as parenteral feeding.
• Gynecological Anomalies: The cervix insertion is low at the superior vaginal wall, close to the introitus. The functions of the uterus and adnexa remain normal. However, the pelvic floor, the levator defect, and the absence of cardinal ligaments cause vaginal prolapse. Mullerian anomalies are also quite common. Reconstructive surgery is often required to improve pelvic floor support and to prevent prolapse complications.

How Is Exstrophy Epispadias Complex Diagnosed?

• It can be diagnosed clinically after birth by inspection.
• Laboratory studies include basic metabolic panels, which can help assess renal function.
• Imaging studies include sonography as a primary study and magnetic resonance imaging (MRI).
• Prenatal diagnosis through ultrasound can help identify the condition early, providing time for parents and the care team to plan surgical and post-surgical care.
• Histologic studies.

How Is Exstrophy Epispadias Complex Treated?

The treatment includes the following surgical modalities:

• Bladder exstrophy repair.
• Functional bladder reconstruction.
• Urinary diversion.
• Male genital reconstruction.
• Female genital reconstruction.
• Osteotomy.
• Modern Staged Repair of Bladder Exstrophy (MSRE): This surgical approach can be performed in phases to restore normal anatomy and function. The first phase, typically performed within days of birth, involves bladder and abdominal wall closure. Epispadias repair may be done during later surgeries.
• Complete Primary Repair of Bladder Exstrophy (CPRE): This is another method that combines bladder closure, bladder neck reconstruction, and epispadias repair in one procedure. It is typically performed at six to eight weeks of age.

What Is the Prognosis for Exstrophy Epispadias Complex?

The prognosis for exstrophy epispadias complex varies according to the treatment modality adopted.

• Post-functional Reconstruction: Continence is achieved in up to 80 percent of cases in childhood. Exstrophy bladders can be preserved, but spontaneous voiding may not be guaranteed; after childhood, bladder augmentation or self-catheterization may be needed.
• Reconstruction Failure: It occurs after a functional reconstruction.
• Post-urinary Diversion: Most individuals require alkalizing drugs to prevent hyperchloremic acidosis, leading to impaired bone mineralization and growth deficiency. Severe long-term complications include adenocarcinomas.
• CPRE: Compared to the MSRE approach, it has shown promise for improving bladder cycling, continence, and overall bladder function. However, lifelong management of complications such as incontinence and kidney function is still needed.
• Fertility and Genital Outcome: Individuals may be concerned about penile size, orientation, and avoidance of sexual interaction. In females, fertility is not affected, although pelvic prolapse can impact sexual satisfaction.

What Is the Risk of Malignancy of the Exstrophy Bladder?

In 50 percent of cases, hamartomatous polyps are on the exstrophy bladder's surface. The polyps are reactive potential pre-malignant environmental changes. Therefore, it is recommended to close the bladder template within the first few hours of birth.

Conclusion

Exstrophy epispadias complex is a spectrum of congenital disabilities, including genitourinary malformations ranging from epispadias to bladder exstrophy and exstrophy of the cloaca. It is characterized by a lower abdominal defect. Therefore, a multidisciplinary team must help the affected individuals and their parents through childhood and adolescence.