Urogenital Adysplasia Syndrome Health Article

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).