Information on the following diseases can be found in the Related Disorders section of this report:

• Exstrophy of the Cloaca Sequence

The bladder-exstrophy-epispadias-cloacal exstrophy complex can take many forms depending on the extent of the developmental abnormality that causes it. The mildest form is when there is an opening in the urethra (epispadias). The most severe form is when there is an opening in the urethra, bladder and bowel (cloacal exstrophy).

The most common form is classic bladder exstrophy in which the bladder and related structures are turned inside out through an opening in the abdominal wall. Classic bladder exstrophy is intermediate in severity and the bladder is open from the top of the bladder through the urethra and to the tip of the penis.

Boys with epispadias have a urethra that is extremely short and split and the opening is on the upper surface of the penis. Girls with epispadias have a urethral opening located between a split clitoris and labia minor.

Cloacal exstrophy is a severe birth defect in which there is usually a membrane-covered area on the abdominal wall that contains the abdominal contents (omphalocele). The bladder is divided in two halves and males have a penis split in two halves. Females have a clitoris divided in two halves and may have two vaginal openings. The opening of the rectum to the outside of the body is usually missing or abnormally small.

Other abnormalities are sometimes associated with the complex. These include a separation of the pubic bones, absence of the lower portion of the bladder causing lack of bladder control (incontinence) and abnormal position of the tubes that carry urine from the kidneys to the bladder (ureters) causing back up of urine in the kidneys (reflux),

In normal development, the cloacal membrane temporarily separates the urogenital and anal structures and them breaks when tissue that will form abdominal muscles begins to grow in its place. The bladder exstrophy-epispadias-cloacal exstrophy complex is caused by a developmental abnormality that occurs 4-5 weeks after conception in which the cloacal membrane is not replaced by tissue that will form the abdominal muscles. The underlying cause of this error in development is not known.

The birth prevalence of classic bladder exstrophy has been estimated to be between 1 in 10,000 and 1 in 50,000 livebirths. Males are affected 2-3 times more often than females. Isolated epispadias occurs in approximately 1 in 112,000 live male births and 1 in 400,000 live female births. Cloacal exstrophy occurs in approximately 1 in 400,000 livebirths.

Diagnosis
Prenatal ultrasound examination of a fetus with the complex may reveal absence of bladder filling, low-set umbilical cord, separation of pubic bones, small genitals and an abdominal mass that increases in size as the pregnancy progresses.

Treatment
The treatment of bladder exstrophy consists of a series of corrective surgeries performed over several years. The first surgery is closure of the bladder to allow it to hold urine, placement of the bladder inside the pelvis and closure of the abdominal wall. In some cases, children with bladder exstrophy may also require a series of surgical procedures to reconstruct the external genitalia. These surgeries are usually performed before the age of 2 years. Bladder neck reconstruction is performed at approximately 5 years of age to allow control of urine and ureters are repositioned to prevent urine from backing up into the kidneys.

The outlook for maintaining normal kidney function after surgical correction and reconstruction is good. However, some individuals with this disorder may experience long-term urinary problems such as kidney stones, kidney infections, and varying degrees of urinary incontinence. Other treatment is symptomatic and supportive.

The use of three-dimensional CT to evaluate the bony pelvis and pelvic floor is being explored. This may provide new insight for long-term issues such as urinary and fecal incontinence and pelvic organ prolapse and help in developing better techniques for reconstruction of the pelvic bones and pelvic floor (osteotomy) in these patients.

Researchers at the Johns Hopkins Institute of Genetic Medicine and the Brady Urology Institute are seeking to identify genes and environmental factors that cause exstrophy and epispadias. For more information on this study, please contact:

McKusick-Nathans Institute of Genetic Medicine
The Johns Hopkins Hospital, CMSC 1004
600 N. Wolfe Street
Baltimore, MD 21287-4822 USA
Phone: (410) 502-6067

Simeon A. Boyd, M.D.
Assistant Professor of Genetic Medicine and Pediatrics
sboyd@mail.jhmi.edu

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