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 Table of Contents  
Year : 2016  |  Volume : 4  |  Issue : 2  |  Page : 235-237

Classification conundrum: Persistent mullerian duct syndrome with hypospadias

1 Department of Pathology, ESIC Medical College, Faridabad, Haryana, India
2 Department of Pathology, VMMC and Safdarjung Hospital, New Delhi, India

Date of Web Publication20-Dec-2016

Correspondence Address:
Sheetal Arora
Assistant Professor, ESIC Medical College, Faridabad, Haryana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2321-4848.196187

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The disorders of sex development (DSD) are uncommon and have wide phenotypic variation. Due to this, they often cannot be classified properly and go unreported. This case is an 18-month-old child with penoscrotal hypospadias with bilateral undescended testes. The karyotyping was 46 XY. Serum testosterone and progesterone were normal. Histopathological examination showed the right gonad with few testicular tubules containing sertoli cells and fibro-collagenization of the stroma. The left Mullerian structures showed epididymis with fallopian tube, with absent testis. Persistent Mullerian duct with hypospadias is a rare anomaly, not classifiable under any of the 46 XY DSD. The possible genesis of this unique case is due to markedly reduced sertoli cells producing low levels of anti-Mullerian hormone which led to the failure of regression of Mullerian duct structures. The associated hypospadias is probably because of impaired action of testosterone possibly due to the deficiency of 5β reductase enzyme.

Keywords: Hypospadias, Mullerian, pseudohermaphroditism

How to cite this article:
Arora S, Mandal AK. Classification conundrum: Persistent mullerian duct syndrome with hypospadias. Arch Med Health Sci 2016;4:235-7

How to cite this URL:
Arora S, Mandal AK. Classification conundrum: Persistent mullerian duct syndrome with hypospadias. Arch Med Health Sci [serial online] 2016 [cited 2023 Mar 23];4:235-7. Available from: https://www.amhsjournal.org/text.asp?2016/4/2/235/196187

  Introduction Top

The disorders of sex development (DSD) are uncommon with an incidence of 1:4500–1:5000 live births.[1] Out of this, persistent Mullerian duct syndrome (PMDS) is still rarer form of male pseudohermaphroditism in which Mullerian derivatives (cervix, vagina, and  Fallopian tube More Details) are present in an otherwise phenotypically male with normal XY karyotype.[2] There are two anatomic types which are classified as “male” or “female”.[3] The male type is more commonly encountered. The less common female type is characterized by bilateral cryptorchidism. Our case belonged to this rare female type of PMDS. This case also had hypospadias, which makes it rarest of the rare case. Thus, this type of DSD cannot be put under a particular category of 46 XY DSD classification.[4] We also propose a possible genesis of this developmental disorder.

  Case Report Top

An 18-month-old child was brought to the outpatient department of Safdarjung Hospital, New Delhi, with chief complaints of passing urine from the ventral surface of penis since birth along with bilateral undescended testes. On examination, penoscrotal hypospadias was seen with bilateral undescended testes. Chromosomal analysis revealed a 46 XY karyotype. Magnetic resonance imaging pelvis showed bilateral pelvic gonads. The left gonad was in the inguinal canal and the right gonad was in the superficial inguinal ring along with a small Mullerian structure in pelvis. Genitogram was done which showed male type of urethra with a vagina along with a common urogenital sinus. Biochemical investigations revealed normal serum testosterone (40.28 ng/dl) and normal 17 α OH progesterone (0.8 ng/ml).

A laparotomy was performed by the pediatric surgeon, and bilateral Mullerian structures were excised along with the left gonadectomy and the right orchiopexy.

Grossly, the right Mullerian structures showed two gray-brown linear cords such as soft tissue pieces measuring 7 cm × 0.3 cm × 0.2 cm and 1 cm × 0.3 cm × 0.2 cm. On sectioning, no lumen could be identified. The right gonadal tissue was gray-brown measuring 0.5 cm × 0.2 cm × 0.2 cm. The left Mullerian structures consisted of two gray-brown soft tissue pieces, one was linear cord-like structure measuring 4 cm × 0.2 cm × 0.2 cm and the other was an irregular soft tissue piece measuring 1 cm × 0.2 cm × 0.2 cm. The left gonadectomy showed a single gray-brown soft tissue piece measuring 3 cm × 1.5 cm × 0.6 cm with an attached tube/cord-like structure measuring 1.5 cm × 1 cm × 0.8 cm.

Microscopy of the right gonadal biopsy revealed few isolated islands of seminiferous tubules separated by fibro-collagenous area. The seminiferous tubules show reduced number of  Sertoli cells More Details [Figure 1] and [Figure 2]. Leydig cells were scattered in the interstitium in between the seminiferous tubules while the left gonadal tissue did not reveal any testicular tissue and showed only fallopian tube. The left Mullerian structures showed epididymis along with a fragment of fallopian tube placed adjacent to epididymis [Figure 3] and [Figure 4]. No Mullerian structures were identified on the right side.
Figure 1: The right gonad showing few isolated islands of testicular tubules separated by fibrocollagenous tissue (H and E, ×4).

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Figure 2: The right testes showing reduced number of sertoli cells in testicular tubules (H and E, ×10).

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Figure 3: Gonad showing epididymis with fallopian tube (H and E, ×4).

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Figure 4: The left gonad showing fallopian tube (H and E, ×10).

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  Discussion Top

Male phenotypic development can be viewed as a two-step process:[5] (1) Testes formation from the primitive gonad and (2) internal and external genitalia differentiation by the action of factors secreted by the fetal testes (sexual differentiation). The first step is very complex and involves interplay of several transcription factors and signaling proteins. The second step, male sex differentiation, is a much simpler and easily understandable process. In our case, the defect lies in Mullerian duct regression implying that the defect is probably at the second step.

The Wolffian duct differentiation appeared to be normal which led to the male type of phenotypic differentiation and genotypically also the child was male. The Mullerian duct structures persisted due to incomplete regression, possibly because of reduced anti-Mullerian hormone (AMH). AMH is produced by the sertoli cells,[6] and the sertoli cells were markedly reduced in the testicular tissue, suggesting the possibility that decrease in the production of AMH prevented the Mullerian duct regression. The stabilization and differentiation of the Wolffian ducts are mediated by testosterone synthesized by the fetal Leydig cells. In this case, normal Leydig cells were seen in the testicular tissue along with normal serum testosterone levels.

According to the classification of 46 XY DSD,[4] our case did not fall into any one category as it showed features of PMDS along with hypospadias. Thus, our case is a unique case showing features of PMDS along with hypospadias (ectopic opening of the urethral meatus).

5α-dihydrotestosterone (5α-DHT) is needed for the normal differentiation of urogenital sinus and male external genitalia such as formation of male urethra and prostrate. 5α-DHT is formed from testosterone by 5α-reductase enzyme. This enzyme exists in two isoenzyme forms Type 1 and Type 2. Type 1 which is expressed in the skin and a few other tissues causes migration of skin fibroblasts to fully enclose the urethral groove in fetal males, normally resulting in an enclosed penile urethra. This phenomenon was lacking in our case. Thigpen et al.[7] showed that deficiency of the 5α reductase enzyme is one of the causes of impaired testosterone action in the fetus. It results in male pseudohermaphroditism.[8],[9] Affected individuals suffer from syndrome called perineoscrotal hypospadias where the external genitalia fail to virilize while the Wolffian duct derivatives (epididymis, vas deferens, and seminal vesicle) develop normally [8] as was seen in our case.


We wish to acknowledge the contribution made by Dr. Manushree Gupta toward preparation and review of this report.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Hamerton JL, Canning N, Ray M, Smith S. A cytogenetic survey of 14,069 newborn infants. I. Incidence of chromosome abnormalities. Clin Genet 1975;8:223-43.  Back to cited text no. 1
Crankson SJ, Bin Yahib S. Persistent Mullerian duct syndrome in a child: Surgical management. Ann Saudi Med 2000;20:267-9.  Back to cited text no. 2
Guerrier D, Tran D, Vanderwinden JM, Hideux S, Van Outryve L, Legeai L, et al. The persistent Müllerian duct syndrome: A molecular approach. J Clin Endocrinol Metab 1989;68:46-52.  Back to cited text no. 3
Renu D, Rao BG, Ranganath K, Namitha. Persistent Mullerian duct syndrome. Indian J Radiol Imaging 2010;20:72-4.  Back to cited text no. 4
[PUBMED]  Medknow Journal  
Mendonca BB, Domenice S, Arnhold IJ, Costa EM. 46, XY disorders of sex development (DSD). Clin Endocrinol (Oxf.) 2009;70:173-87.  Back to cited text no. 5
Josso N, Belville C, di Clemente N, Picard JY. AMH and AMH receptor defects in persistent Müllerian duct syndrome. Hum Reprod Update 2005;11:351-6.  Back to cited text no. 6
Thigpen AE, Davis DL, Milatovich A, Mendonca BB, Imperato-McGinley J, Griffin JE, et al. Molecular genetics of steroid 5 alpha-reductase 2 deficiency. J Clin Invest 1992;90:799-809.  Back to cited text no. 7
Walsh PC, Madden JD, Harrod MJ, Goldstein JL, MacDonald PC, Wilson JD. Familial incomplete male pseudohermaphroditism, type 2. Decreased dihydrotestosterone formation in pseudovaginal perineoscrotal hypospadias. N Engl J Med 1974;291:944-9.  Back to cited text no. 8
Imperato-McGinley J, Guerrero L, Gautier T, Peterson RE. Steroid 5alpha-reductase deficiency in man: An inherited form of male pseudohermaphroditism. Science 1974;186:1213-5.  Back to cited text no. 9


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


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