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CASE REPORT Table of Contents   
Year : 2010  |  Volume : 53  |  Issue : 2  |  Page : 313-315
Mixed gonadal dysgenesis with normal karyotype : A rare case report


Departments of Urology and Pathology, All India Institute of Medical Sciences, New Delhi - 110 029, India

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Date of Web Publication12-Jun-2010
 

   Abstract 

Mixed gonadal dysgenesis (MGD) presents as a unilateral testis, usually intraabdominal, a streak gonad on contralateral side, and persistent mullerian structures. 45X/45XY karyotype is most frequent in such cases with predominance of 45X cells in both peripheral lymphocytes and gonads. We present a rare case of a left undescended testis, normally descended right testis, with penoscrotal hypospadias, who had a normal karyotype and whose histopathological findings were endometrial tissue and fallopian tube in left testicular biopsy. Gonadal dysgenesis should always be kept a possibility in patient with undescended testis and proximal hypospadias. If karyotype reveals a 46XY gonadal dysgenesis, these patients need all the more careful follow-up to screen for gonadoblastoma in remaining normal testis. Subjecting the patients to prophylactic orchidectomy with hormone replacement can be an additional option in such patients.

Keywords: Hypospadias, mixed gonadal dysgenesis, undescended testis, 46XY karyotype

How to cite this article:
Anand A, Gupta NP, Singh M K, Mathur SR, Nayyar R. Mixed gonadal dysgenesis with normal karyotype : A rare case report. Indian J Pathol Microbiol 2010;53:313-5

How to cite this URL:
Anand A, Gupta NP, Singh M K, Mathur SR, Nayyar R. Mixed gonadal dysgenesis with normal karyotype : A rare case report. Indian J Pathol Microbiol [serial online] 2010 [cited 2019 Dec 7];53:313-5. Available from: http://www.ijpmonline.org/text.asp?2010/53/2/313/64297



   Introduction Top


Sohval [1] in 1963 coined the term 'mixed gonadal dysgenesis,' which is characterized by unilateral testis, which is often intraabdominal, a contralateral streak gonad, and persistent mullerian structures associated with varying degrees of inadequate masculinization. Most common karyotype in such patients is 45XO/46XY. [2] Uterus, vagina and  Fallopian tube More Details are present in virtually all of these patients; with short stature and associated somatic stigmata presenting as variable features. Testicular androgenic function appears to be quantitatively and qualitatively normal at puberty in MGD (Mixed Gonadal Dysgenesis), despite complete lack of germ-cell proliferation. [3]


   Case Report Top


We present a unique case of a left undescended testis, normally descended right testis, with penoscrotal hypospadias, who had a normal karyotype and whose histopathological findings were endometrial tissue and fallopian tube in left testicular biopsy.

A 16-year-old male child, second in order of birth, with full-term normal delivery at home, 30 kg in weight, 135 cm in height, presented with left undescended inguinal testis and penoscrotal hypospadias. Right testis was normally descended and of normal size. Patient had history of small penis, which however increased in length after receiving HCG (human chorionic gonadotropin) 5000 units/L intravenously biweekly for three months at age of 15 years. Patient had history of normal erections. His ultrasonogram revealed right testis of 2.3 x 1.02 cm seen in scrotal sac whereas left testis was undescended. Rest of the intraabdominal findings was normal on ultrasonogram of abdomen. His serum testosterone was 4.51 nmol, LH was 1.70 U/L, FSH was 2.50 U/L and prolactin was 6.20 μg/L. Patient was taken up for diagnostic laparoscopy at age of 16 years. No testis could be identified on laparoscopy. Gonadal vessels and vas deferens were seen going into the inguinal canal. Groin incision was made and streak atrophic gonad was identified, removed and sent for histopathological examination. On histopathological evaluation, the streak gonadal tissue revealed presence of endometrial glands and stroma [Figure 1], along with fallopian tube structure [Figure 2]. No gonadal tissue (streak or normal) was identified in the resected specimen. However, vas was identified on histopathological examination of streak gonad. The aspiration smears from right testis showed preponderance of  Sertoli cells More Details along with a few spermatogenic cells. Mature spermatozoa were however not seen [Figure 3].

Patient's karyotype was done, which was 46XY. Simultaneous correction of chordee by dorsal plication with Byar's flap was done, with second stage closure of penoscrotal hypospadias (tubularization) done ten months later. Patient was phenotypically male but had short stature and not so well-developed secondary sexual character.


   Discussion Top


Mixed gonadal dysgenesis (MGD) is an intersex genetic abnormality characterized by a streak gonad and a contralateral testis (that is typically cryptochid), a bilateral streak testis. A uterus and one or both fallopian tubes may be present. External genitalia may be frequently ambiguous. [4]

Mixed gonadal dysgenesis patients are always chromatin negative and appear to represent the commonest expression of mosaicism of XO and XY cells, probably existing from a cytogenetic abnormality early on in embryogenesis. [2]

Irregular maturation of Sertoli cells appears to be a feature of MGD. However, while the patient appeared to show features of MGD along with endometrial tissue and fallopian tube in left testicular biopsy specimen and Sertoli cells in right testis, the karyotype turned out to be 46XY.

That presentation of MGD with a normal karyotype 46XY, as seen in our patient, is extremely rare. This patient had normal baseline levels of pituitary gonadotrophin and testosterone and his gonadal response to HCG was favorable.

Additional information on structural abnormalities involving the testis, determining gene of Y-chromosome in patients with MGD, is needed in order to further understand the mechanisms responsible for the male variability characteristic of this disease. Sagodi et al.[4] reported a case of MGD with a karyotype containing iso-dicentric Y chromosome in mosaic form. They emphasized necessity of special investigations of newborn with penoscrotal hypospadias and bilateral or unilateral mal-descended testes immediately after birth.

Proto et al.[5] reported a case of MGD, with a mosaic karyotype consisting of two cell lines, one with 45 chromosomes and monosomic X (50%), the other with 46 chromosomes and one Y dicentric chromosome (50%). The patient presented a male phenotype, hypospadias (3rd degree), left cryptorchidism, hypotrophic right testis, short stature and a gonadal asymmetry. Le Caignec et al.[6] reported a large kindred of 46XY gonadal dysgenesis in which various disorders of sexual development were observed, ranging from completely female phenotype without ambiguities of the external genitalia (five cases) to men with isolated penile or perineal hypospadias (four cases), including two cases with moderate virilization and one case with ambiguity of the external genitalia. Presence of hermaphrodite genitals in patient or a higher degree of hypospadias with mal-descended testis necessitate to identify chromosomal disorder as cause of this anomaly.

Lukusa et al.[7] stressed the importance of gonadal dysgenesis in the genesis of gonadoblastoma in the presence of the Y-chromosome.

46XY gonadal dysgenesis is transmitted as an autosomal dominant trait in a large family with multiple affected members. [8]

Our case was suspected to be having MGD, on histopathological examination of left testicular tissue. However, conclusive evidence of MGD can be done only on histopathological demonstration of a streak testicular tissue in the gonad along with the Mullerian structures. It is essential to differentiate it from another condition called Persistent Mullerian Duct Syndrome (PMDS), which also presents with 46XY karyotype and normal male external genitalia but internal Mόllerian duct structures. Typically, these phenotypic males have unilateral or bilateral undescended testes, bilateral fallopian tubes, a uterus, and an upper vagina draining into a prostatic utricle. The condition is commonly diagnosed after Mόllerian tissue is encountered during inguinal herniorrhaphy or orchidopexy. Unfortunately, no testicular tissue (streak or normal) was identified in the resected specimen in our case to conclusively label this case as MGD or PMDS. In absence of histopathological evidence showing a streak gonad, our proposition of this case being MGD is based on clinical evidence including short stature, somatic stigmata, contralateral descended testis, unambiguous male genitalia with penoscrotal hypospadias and absence of upper vagina draining into the prostatic utricle. This patient had short stature (135 cm) at age of 17 years with proximal hypospadias. Correction of hypospadias was done. He continues to be under our follow-up for last about 18 months with no complaints. There was no familial history of MGD. Patients with undescended testis and proximal hypospadias, particularly in the presence of short stature, can have MGD even in the presence of normal karyotype. These patients are at high risk of developing gonadoblastoma in opposite testis, and thus, need continuous and scrupulous follow-up. Such patients should ideally be counseled for prophylactic orchidectomy of normal testis with hormone replacement, so as to nullify chances of developing gonadoblastoma.


   Conclusion Top


Gonadal dysgenesis should always be kept a possibility in patient with undescended testis and proximal hypospadias. If karyotype reveals a 46XY gonadal dysgenesis, these patients need all the more careful follow-up to screen for gonadoblastoma in remaining normal testis. Subjecting the patients to prophylactic orchidectomy with hormone replacement can be an additional option in such patients.

 
   References Top

1.Sohval AR. "Mixed" Gonadal Dysgenesis: a variety of hermaphroditism. Am J Hum Genet 1963;15:155-8.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]  
2.Davidoff F, Federman DD. Mixed gonadal dysgenesis. Pediatrics 1973;52:725-42.  Back to cited text no. 2  [PUBMED]    
3.Raff R, Schubert R, Schwanitz G, Van der Ven K, Bruhl P. Undescended testis and hypopadias in sex chromosomal observations. Klin Padiatr 1998;210:400-5.  Back to cited text no. 3      
4.Sagodi L, Solyom E, Totha A, Kekesi A, P tardy E, Borbas E, et al. Mixed gonadal dysgenesis associated with an isodicentric Y chromosome. Orv Hetil 2007;148:1567-71.  Back to cited text no. 4      
5.Proto G, Bartolomei P, Mazzolini A, Grimaldi F, Torossi I, Bertolissi F. Mixed gonadal dysgenesis (MGD). Description of a case. Minerva Endocrinol 1991;16:203-6.  Back to cited text no. 5  [PUBMED]    
6.Le Caignec C, Baron S, McElreavey K. 46, XY gonadal dysgenesis: evidence for autosomal dominant transmission in large kindred. Am J Med Genet A 2003;116:37-43.  Back to cited text no. 6      
7.Lukusa T, Fryns JP, Kleczkowrska F, Van den Berghe H. Role of gonadal dysgenesis in gonadoblastoma induction in 46, XY individuals. The Leuven experience in 46, XY pure gonadal dysgenesis and testicular ferminization syndromes. Genet Couns 1991;2:9-16.  Back to cited text no. 7      
8.Jawaheer D, Juo SH, Le Caignec C. Mapping a gene for 46, XY gonadal dysgenesis by linkage analysis. Clin Genet 2003;63:530-5.  Back to cited text no. 8      

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Correspondence Address:
Narmada P Gupta
Departments of Urology and Pathology, All India Institute of Medical Sciences, New Delhi - 110 029
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.64297

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    Figures

  [Figure 1], [Figure 2], [Figure 3]

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