Research Letter Exclusion of WNT4 as a Major Gene in Rokitansky-Kuster-Hauser Anomaly

Unite´INSERM U-493, 32 rue des Carnets, 92140 Clamart, FranceTo the Editor:Rokitansky-Ku¨ster-Hauser (RKH) anomaly [Ludwig, 1998]comprises absence of vagina and rudimentary uterus in 46,XXindividuals with normal ovaries, normal secondary sexualcharacteristics, and normal chromosomes. Two variants ofRKH syndrome are distinguished on the basis of laparoscopyfindings [Strubbe et al., 1993; Acien et al., 2004]: (i) typicalcases with uterus reduced to symmetrical and non-canalizedmuscular bud with normal fallopian tubes, (ii) atypical RKHwithasymmetricalmuscularbudsorabnormalfallopiantubes.In those later cases, abnormalities of the urinary tract arecommon such as agenesis, ectopy, malrotation of one kidney(renal adysplasia sequence [Opitz, 1987], and less commonskeletal anomalies suggesting embryological links betweengenitourinary and bone development.The cause of the RKH anomaly remains unknown; butseveral reports of familial cases, mostly affected sisters, sug-gest that the RKH anomaly may be due to a female-limitedautosomal dominant trait with variable expression and reduc-ed penetrance [Anger et al., 1966; Jones and Mermut, 1972].Recently, a heterozygous WNT4 gene missense mutation wasreported in a woman with primary amenorrhea, absence ofmu¨llerian derivatives, unilateral renal agenesis and signs ofvirilization, a phenotype resembling RKH anomaly [Biason-Lauber et al., 2004]. This finding and the Wnt4