Picard Jean-Yves, Cate Richard L, Racine Chrystèle, Josso Nathalie
Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
Sex Dev. 2017;11(3):109-125. doi: 10.1159/000475516. Epub 2017 May 20.
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.
男性性别分化由两种激素驱动，即睾酮和抗苗勒管激素（AMH），它们负责男性胎儿苗勒管的退化。使AMH或其受体AMHRII失活的突变会导致原本正常男性化的46,XY男性出现持续性苗勒管综合征（PMDS）。我们的目的是基于文献综述和157例个人病例，回顾PMDS的临床、解剖和分子特征。存在三种临床表现：双侧隐睾、单侧隐睾伴对侧疝气以及睾丸横位异位。男性排泄管异常很常见。33%的成年患者会发生睾丸恶性变性，而苗勒管衍生物癌则较少见。生育能力罕见，但如果至少有一个睾丸位于阴囊内且其排泄管完整，则有可能生育。已鉴定出80个家族，其中AMH基因有64种不同突变，主要位于外显子1、2和5。在75个家族中发现了代表58个不同等位基因的AMHRII基因突变。最常见的突变是激酶结构域中的27个碱基对缺失，在30名大多来自北欧的患者中发现。在12%的病例中，未检测到AMH或AMHRII的突变，这表明参与苗勒管退化的其他途径受到了破坏。
