Persistent Müllerian duct syndrome
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|Persistent Müllerian duct syndrome|
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Persistent Müllerian duct syndrome (PMDS) refers to the presence of a uterus and sometimes other Müllerian duct derivatives in a genetically male animal. In humans, PMDS typically is due to an autosomal recessive congenital disorder and is considered by some to be a form of pseudohermaphroditism due to the presence of uterine tissue.
Typical features include undescended testes (cryptorchidism) and the presence of a small, underdeveloped uterus in a genetically male infant or adult. This condition is usually caused by deficiency of fetal anti-Müllerian hormone (AMH) effect due to mutations of the gene for AMH or the anti-Müllerian hormone receptor.
AMH (Anti Müllerian Hormone) is produced by the primitive Sertoli cell as one of the earliest Sertoli cell products and induces regression of the Müllerian ducts. Müllerian ducts are only sensitive to AMH action around the 8th week of amenorrhea and Müllerian regression is completed by the end of the 9th week. The AMH induced regression of the Müllerian duct occurs in cranio-caudal direction via apoptosis. The AMH receptors are located on the Müllerian duct mesenchyme and transfer the apoptotic signal to the Müllerian epithelial cell presumably via paracrine actors. The Wolffian ducts differentiate into epididymides, vasa deferentia and seminal vesicles under the influence of testosterone, produced by the fetal Leydig cell
Because both the Wolffian ducts and Müllerian ducts begin to develop, the tissues are often intertwined, resulting in obstruction or nonpatency of the vas deferens or other parts of the male excretory ducts. This can result in infertility, the most serious potential problem caused by this condition.
The condition can come to attention because of a bulge in the inguinal canal of a genetically male infant due to herniation of the uterus. The presence of a uterus may be noticed if an ultrasound or MRI of the pelvis is performed to locate the testes or for other reasons. Occasionally the uterus is discovered during abdominal surgery for some other purpose in later childhood or adult life.
Although persistent Müllerian duct syndrome is classified as an intersex condition, it does not involve ambiguity or malformation of the external genitalia, which appear typically male (apart from cryptorchidism if present).
Apart from humans, this syndrome has been reported in dogs.
Surgery (orchiopexy) to retrieve the testes and position them in the scrotum is the primary treatment. Occasionally they are unsalvageable if located high in the retroperitoneum. During this surgery, the uterus is usually removed and attempts made to dissect away Müllerian tissue from the vas deferens and epididymis for the purpose of improving the chance of fertility. If the person has male gender identity and the testes cannot be retrieved, testosterone replacement will be necessary at puberty . Lately, laparascopic hysterectomy is offered to patients as a solution to both improve the chances of fertility and to prevent the occurrences of neoplastic tissue formation.
Molecular genetics and inheritance
PMDS type II results from mutations of the gene (AMH-RII) for the AMH receptor on 12q13.
Both types of disorders are inherited as autosomal recessive conditions with expression usually limited to genetic males.
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- Colacurci, N.; A.Cardone, P.De Franciscis, E.Landolfi, T.Venditto, A.A.Sinisi (1997-12-02). "Laparoscopic hysterectomy in a case of male pseudohermaphroditism with persistent Müllerian duct derivatives". European Society of Human Reproduction and Embryology (Oxford University Press) 12 (2): 272–274. doi:10.1093/humrep/12.2.272. ISSN 1460-2350. Retrieved 2009-05-17.
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- Grzegorz Kudela, Mirosław Mikosiński, Wojciech Utrata, Elżbieta Kuleta-Bosak, Barbara Kalina-Faska, Tomasz Koszutski (2008). "Persistent Müllerian Duct Syndrome – Familiar Occurrence". J. Urologia Polska 61 (3). ISSN 0500-7208.
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- Online 'Mendelian Inheritance in Man' (OMIM) 600957
- Online 'Mendelian Inheritance in Man' (OMIM) 600956