Müllerian Anomalies and Renal Agenesis: Autosomal Dominant Urogenital Adysplasia

Abstract

We report two families in which mullerian anomalies or renal agenesis appeared to be caused by an autosomal dominant gene that produces unilateral or bilateral renal agenesis and a spectrum of mullerian anomalies. This single gene disorder may account for the high incidence of mullerian anomalies observed in females with bilateral renal agenesis and the increased frequency of renal anomalies in patients with mullerian malformations. The range of mullerian anomalies in this disorder includes bicornuate uterus, uterus didelphys, Rokitansky- Kuster -Hauser syndrome (vaginal atresia with or without absence of the uterus), and total mullerian aplasia. Gene expression is not sex limited. Affected males can have bilateral or unilateral renal agenesis, and possibly may have unilateral or bilateral absence of the vas deferens or seminal vesicles. We suggest that autosomal dominant urogenital adysplasia is common, but underdiagnosed because of the deceptive variability in gene expression. In addition, reduced gene penetrance and reduced biologic fitness from lethal renal anomalies or genital tract anomalies may obscure the autosomal dominant nature of this disorder in most families.