The Persistent Müllerian Duct Syndrome: An Update Based Upon a Personal Experience of 157 Cases

Abstract

Male sex differentiation is driven by 2 hormones, testosterone and anti-müllerian hormone (AMH), responsible for the regression of müllerian ducts in male fetuses. Mutations inactivating AMH or its receptor AMHRII lead to the persistent müllerian duct syndrome (PMDS) in otherwise normally virilized 46,XY males. Our objective was to review the clinical, anatomical, and molecular features of PMDS based upon a review of the literature and upon 157 personal cases. Three clinical presentations exist: bilateral cryptorchidism, unilateral cryptorchidism with contralateral hernia, and transverse testicular ectopia. Abnormalities of male excretory ducts are frequent. Testicular malignant degeneration occurs in 33% of adults with the disorder, while cancer of müllerian derivatives is less frequent. Fertility is rare but possible if at least one testis is scrotal and its excretory ducts are intact. Eighty families with 64 different mutations of the AMH gene have been identified, mostly in exons 1, 2, and 5. AMHRII gene mutations representing 58 different alleles have been discovered in 75 families. The most common mutation, a 27-bp deletion in the kinase domain, was found in 30 patients of mostly Northern European origin. In 12% of cases, no mutation of AMH or AMHRII has been detected, suggesting a disruption of other pathways involved in müllerian regression.

A Novel Homozygous <b><i>AMRH2</i></b> Gene Mutation in a Patient with Persistent Müllerian Duct Syndrome

“…The rate of consanguinity in families with AMHR2 mutations is high (33%), but it is only 10% in idiopathic PMDS. The rate of homozygosity of AMHR2 mutations varies in different parts of the world, with a mean of 57%, although Asia was not represented [ Picard et al, 2017]. The first AMHR2 mutation was described in 1995 [Imbeaud et al, 1995].…”

“…The first AMHR2 mutation was described in 1995 [Imbeaud et al, 1995]. Since then, based on a review of Picard et al [2017] [Qin et al, 2014;Baxter et al, 2015;Eggers et al, 2016;Orós-Millán et al, 2017;Ren et al, 2017;Picard et al, 2017;Çakir et al, 2017;Unal et al, 2018]. The mutations that are not included in Picard et al [2017] are listed in Table 1 together with the present variant.…”

“…es [Picard et al, 2017]. There is no phenotypic difference between patients with either AMH or AMHR2 mutations.…”

“…A total of 58 different mutations have been identified to date in AMHR2 [Picard et al, 2017]. All exons are affected and 10 recurrent mutations have been described, being a deletion of 27 bp in exon 10 the most frequent [Picard et al, 2017].…”

“…All exons are affected and 10 recurrent mutations have been described, being a deletion of 27 bp in exon 10 the most frequent [Picard et al, 2017].…”