PERSISTENT MULLERIAN DUCT SYNDROME ASSOCIATED WITH47,XXY GENOTYPE

DANIEL P. DELANEY, THOMAS F. KOLON AND STEPHEN A. ZDERIC*From the Division of Urology, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania

KEY WORDS: pseudohermaphroditism, mullerian ducts/abnormalities, sex chromosome aberrations, sex chromosomedisorders, Klinefelter syndrome

Persistent mullerian duct syndrome (PMDS) is a rare formof male pseudohermaphroditism characterized by the reten-tion of mullerian derivatives in an otherwise normally viril-ized male. Approximately 50% of the cases of PMDS can beattributed to mutations in the mullerian inhibitory sub-stance gene. The remaining cases are primarily the result ofa deletion in the type II receptor of mullerian inhibitorysubstance.1 Karyotypes are obtained in patients with PMDSat the discretion of the physician, to confirm a normal 46,XYchromosomal genotype. To date, PMDS has not been identi-fied with any additional genetic or syndromic findings.

CASE REPORT

A 6-year-old boy was referred for management of bilateralcryptorchidism. The left testis was palpable in the left ingui-nal canal and the right testis was impalpable. Pelvic ultra-sound obtained before initial consultation could not identifymullerian structures or locate the right testis.

At right bilateral orchiopexy the right side was exploredfirst via an inguinal incision. The testis was tethered medi-ally to a thickened structure and gentle traction on the testisresulted in a dimpling of the left groin. A left inguinal inci-sion was made and the left testis was confirmed to be teth-ered to the right side. PMDS was presumptively diagnosed,and the inguinal incisions were converted to a Pfannenstielincision. Exploratory laparotomy revealed an atretic uteruswith bridging fallopian structures (fig. 1). The uterus wassplit along the midline, allowing both testes to be brought toa dependent tensionless position within the scrotum, without

transecting the spermatic vessels or compromising the testes(fig. 2).

Bilateral testis biopsy demonstrated testicular tissue, witha probable absence of germ cells, scattered clusters of smalljuvenile Leydig cells, moderate to severe tubular atrophy andinterstitial fibrosis, numerous calcospherites and absence ofcarcinoma in situ. These biopsies are predictive for a spermcount below 5 to 10 million per ml, and on this basis alone theprognosis for fertility is poor.2 Karyotype evaluation showed47,XXY, consistent with Klinefelter’s syndrome.

DISCUSSION

To our knowledge there are no previously published re-ports of PMDS occurring with Klinefelter’s syndrome. Webelieve it is unlikely that these disorders are related. How-ever, this presentation raises some interesting points. Is itpossible that many patients with Klinefelter’s syndromehave mullerian remnants on the basis of abnormal testicularfunction? Given that most patients with Klinefelter’s syn-drome do not present with undescended testicles, such mul-lerian remnants may have never been discovered. Would anoninvasive assessment with magnetic resonance imaging ofpatients with Klinefelter’s syndrome reveal a higher inci-dence of PMDS? In addition, the karyotyping of patients withPMDS is at the discretion of the physician. Is it possible thatpatients with PMDS and 47,XXY have been overlooked? Theclassic physical findings in Klinefelter’s syndrome will not beapparent if orchiopexies are being performed in infancy. Fi-nally, are patients with PMDS at higher risk for testicularcarcinoma? Recent reports of malignancies in this small pop-ulation cause us to suspect that these patients merit closefollowup, and must be taught how to perform monthly self-examination during the pubertal years.3

Accepted for publication September 26, 2003.Presented at biannual meeting of Society for Fetal Urology, Bos-

ton, Massachusetts, October 18, 2002.* Correspondence: Children’s Hospital of Philadelphia, 34th and

Civic Center Blvd., Division of Urology, Third Floor Wood Building,Philadelphia, Pennsylvania 19104.

FIG. 1. Exploration demonstrates atretic uterus (U) with bridgingfallopian structures (F). T, testis. E, epididymis.

FIG. 2. Uterus was split along midline (arrow), allowing both tes-tes to be brought to dependent tensionless position within scrotumwithout transecting spermatic vessels or compromising testes.

0022-5347/04/1712-0852/0 Vol. 171, 852–853, February 2004THE JOURNAL OF UROLOGY® Printed in U.S.A.Copyright © 2004 by AMERICAN UROLOGICAL ASSOCIATION DOI: 10.1097/01.ju.0000106725.28786.d6

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REFERENCES

1. Lane, A. H. and Donahoe, P. K.: New insights into mullerianinhibiting substance and its mechanism of action. J Endocri-nol, 158: 1, 1998

2. Rusnack, S. L., Wu, H.-Y., Huff, D. S., Snyder, H. M., III, Carr,M. C., Bellah, R. D. et al: Testis histopathology in boys with

cryptorchidism correlates with future fertility potential.J Urol, 169: 659, 2003

3. Bucci, S., Liguori, G., Buttazzi, L., Bussani, R. and Trombetta,C.: Bilateral testicular carcinoma in patient with thepersistent mullerian duct syndrome. J Urol, 167: 1790,2002

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