Urogenital adysplasia syndrome

Definition

Urogenital adysplasia syndrome is a rare disorder characterized by anomalies of the kidneys, urinary tract, and/or reproductive system.

Description

The development of urogenital adysplasia syndrome resulted from the combined work of multiple physicians examining several families. The first report of siblings born with both kidneys missing (bilateral renal agenesis ) was made by H. Madisson in 1934. However, the term hereditary renal adysplasia was not coined until 1973 when R. M. Buchta combined the terms aplasia, the complete absence of one or both kidneys, and dysplasia , developmental anomalies of the kidneys, to form the term adysplasia to apply to familial, bilateral kidney anomalies. In 1980, R. N. Schimke and C. R. King suggested that the developmental defects in certain family's reproductive and urinary tracts (mesonephric and mullerian ducts) may have a common genetic basis and that the designation hereditary urogenital adysplasia should be used as a descriptive syndrome name.

Urogenital adysplasia syndrome is an autosomal dominant inherited condition. The symptoms of urogenital adysplasia syndrome are variable. Affected individuals within families may have features of the disease that include one or two missing kidneys (renal agenesis), one or two malformed kidneys (renal dysplasia), bladder anomalies, ureter abnormalities, hypertension, vaginal anomalies, uterine anomalies, fallopian tube anomalies, lack of a menstrual period (amenorrhea), and cysts of the seminal vesicle. Fetuses that have two missing or very abnormal kidneys are often born with a condition called Potter's sequence, or syndrome. Potter's sequence occurs when the fetal kidneys cannot produce enough amniotic fluid to surround the fetus as it develops. Features of Potter's sequence include wide-set eyes, squashed nose, small and receding chin, low-set ears, deformities of the hands and feet, and incompletely formed lungs (lung hypoplasia).

Urogenital adysplasia syndrome is also referred to as hereditary renal adysplasia (HRA), renal agenesis, and bilateral renal agenesis (BRA). The age of diagnosis for affected individuals often is determined by the symptoms they exhibit. Individuals affected by urogenital adysplasia syndrome may be diagnosed prenatally based on two (bilateral) missing kidneys, at birth based on the features of Potter's syndrome, or not until adulthood with the findings of reproductive problems or one missing kidney.

Genetic profile

The genetic cause of urogenital adysplasia syndrome is not fully understood. Studies in 1995, 1997, 2000, and 2001 found evidence that nonworking, or mutated, genes on the long arm of chromosome 10 (10q) result in the abnormal development of the urogenital tract. However, it is still unclear if the features of urogenital adysplasia syndrome are caused by a single mutation in one gene on chromosome 10q or by mutations in multiple genes found in this and other chromosomal locations.

Although the genetic location and mutations that cause urogenital adysplasia syndrome have not yet been determined, family studies have found that the syndrome is inherited as an autosomal dominant condition. In an autosomal dominant condition, only one mutated copy of a gene is necessary for a person to experience symptoms of the condition. If a parent has an autosomal dominant condition, there is a 50% chance for each of his or her children to have the same or a similar condition. However, in an autosomal condition with variable expressivity and incomplete penetrance like urogenital adysplasia syndrome, individuals inheriting the same mutated copy of a gene in the same family can have very different symptoms.

Demographics

Urogenital adysplasia syndrome is a genetic condition that has been found in individuals descended from a variety of ethnic backgrounds. Although the exact frequency of urogenital adysplasia syndrome is unknown, it can be estimated based upon past family studies. Family studies also indicate that disease symptoms are more severe in males than in females. Between one in 3,000 and 10,000 newborns are born with two severely malformed or missing kidneys (bilateral renal agenesis or dysplasia). It is suggested that urogenital adysplasia syndrome is currently underdiagnosed due to its variability of symptoms within families.

Signs and symptoms

The signs and symptoms of urogenital adysplasia syndrome vary from individual to individual (variable expressivity). Most people diagnosed with urogenital adysplasia syndrome have anomalies in their urinary and reproductive tract. The most common findings include missing kidneys and uterine abnormalities. Specific features may include any of the following:

• one or two missing kidneys (renal agenesis)
• one or two malformed kidneys (dysplastic kidneys)
• bladder anomalies
• hypertension
• vaginal anomalies
• uterine anomalies
• fallopian tube anomalies
• lack of a menstrual period (amenorrhea)
• cysts of the seminal vesicle

Additionally, since Potter's sequence occurs when the fetal kidneys cannot produce enough amniotic fluid to cushion the fetus as it develops, the features of Potter's sequence can suggest a diagnosis of urogenital adysplasia syndrome in a baby with wide-set eyes, squashed nose, small and receding chin, low-set ears, deformities of the hand and feet, and incompletely formed lungs (lung hypoplasia).

Diagnosis

Diagnosis of urogenital adysplasia syndrome is usually made by physical examination by a medical geneticist or other physician, an ultrasound of the kidneys and the urinary and reproductive tracts, and a detailed medical family history.

Prenatal diagnosis of severe cases can sometimes be made using targeted ultrasound imaging during pregnancy to provide pictures of the fetal kidneys, bladder, and amniotic fluid levels. Ultrasound results that may indicate urogenital adysplasia syndrome include low amniotic fluid levels (oligohydramnios) combined with missing or abnormally formed kidneys (renal agenesis or adysplasia). Ultrasonographic screening for parents and siblings of infants born with agenesis or adysplasia of the kidneys is recommended since the diagnosis of urogenital adysplasia syndrome can have implications for their health and medical care. Diagnostic prenatal or postnatal molecular genetic testing is not available as of 2005.

Treatment and management

Urogenital adysplasia syndrome is a genetic condition that has no specific treatment that can remove, cure, or fix its underlying genetic error. Treatment for urogenital adysplasia syndrome is limited to the management of specific symptoms. Individuals with one only kidney should be followed by a nephrologist who can evaluate their need for antihypertensive agents and/or a kidney transplant. Individuals affected by urinary tract anomalies should be followed by an urologist. Individuals with reproductive anomalies can consult an obstetrician/gynecologist who specializes in pelvic reproductive reconstructive surgery for infertility, endometriosis, pelvic pain, and congenital anomalies. Medical geneticists and genetic counselors are available to discuss inheritance patterns of the syndrome and reproductive options with affected individuals. Pregnant women whose fetuses are at risk for urogenital adysplasia syndrome should be evaluated by a perinatalogist or maternal fetal medicine specialist. Other specialists and/or surgeons may be added to an individual's medical team to address specific individual concerns.

Prognosis

Since urogenital adysplasia syndrome results in a variety of different physical symptoms, the prognosis for each affected individual is very different.

Individuals who have one normal kidney and one malformed have an excellent prognosis, and most live normal lives. Individuals who have only one functional kidney may have issues with hypertension and proteinuria.

Individuals with reproductive anomalies may be infertile or have fertility issues. An obstetrician/gynecologist who specializes in pelvic reproductive reconstructive surgery for infertility, endometriosis, pelvic pain, and congenital anomalies may be able, in some cases, to correct some anomalies and restore fertility.

On the most severe end of the spectrum, babies found prenatally to have low amniotic fluid (oligohydramnios) and two missing kidneys (bilateral agenesis or adysplasia) might be miscarried, stillborn, or die after birth due to combined health implications of incompletely formed lungs and missing kidneys.

Resources

BOOKS

Greenburg, Arthur, ed. Primer on Kidney Diseases, 4th Edition. San Diego: Academic Press, 2005.

PERIODICALS

McPherson, E., et al. "Dominantly Inherited Renal Adysplasia." American Journal of Medical Genetics 1987 Apr. 26(4): 863–72.

ORGANIZATIONS

American Association of Kidney Patients. 3505 E. Frontage Rd., Ste. 315 Tampa, FL, 33607-1796. (800) 749-2257. (813) 636-8100. Fax: (813) 636-8122. info@aakp.org. (April 7, 2005.) <http://www.aakp.org/>.

Kidney and Urology Foundation of America, Inc. 1250 Broadway, Suite 2001, New York, NY 10001. (212) 629-9770 or (800) 633-6628. Fax: (212) 629-5652. info@kidneyurology.org. (April 7, 2005.) <http://www.kidneyurology.org/homepage.htm>.

National Kidney Foundation. 30 East 33rd Street, New York, NY 10016. (800) 622-9010. (April 7, 2005.) <http://www.kidney.org/>.

National Potters Syndrome Support Group (NPSSG). 225 Louisiana Street, Dyess AFB, TX 79607. (915) 692-0831. Wright01@Camalott.com. (April 7, 2005.) <http://www.geocities.com/Heartland/Meadows/5586/syndrome.htm>.

WEBSITES

Surgical Management of Mullerian Duct Anomalies.(Last updated: February 19, 2003; April 7, 2005.) <http://www.emedicine.com/med/topic3521.htm>.

Dawn Jacob Laney