Surgical and genetic aspects of persistent müllerian duct syndrome.

Persistent müllerian duct syndrome (PMDS) is characterized by the presence of a uterus, cervix, and fallopian tubes in an otherwise normally differentiated 46.XY male. During embryogenesis, regression of müllerian structures in normal males is mediated by antimüllerian hormone (AMH), also called müllerian inhibiting substance (MIS), produced by fetal Sertoli's cells. PMDS has been attributed to deficient AMH activity or to abnormalities in the AMH receptor. The authors report on two patients with PMDS in whom the abnormalities were discovered during surgery for inguinal hernia and cryptorchidism. During the initial operations in each case, testicular biopsies were obtained, and the gonads and müllerian elements were replaced in the pelvis. A second operative procedure, performed several months later, included proximal salpingectomies with dissection of the vasa deferentia on pedicles of myometrium. This permitted excision of the vestigial uterine corpus, leaving a tiny remnant of cervix with the vasa deferentia. The testes were further mobilized so that bilateral orchidopexies could be completed. In the first case, a molecular abnormality was present at position 377 of the first exon of the AMH gene. Thymine replaced cytosine, which altered a CGG arginine codon to a TGG tryptophan codon, rendering the AMH molecule unstable. The molecular abnormality in the first case differs from the first abnormality in AMH reported by Knebelmann et al, thus indicating heterogeneity in this condition. The molecular basis for deficient AMH activity in the second patient has not yet been defined. No molecular abnormalities were found in the exons of this patient's AMH gene.