Diagnosis Of Mixed Gonadal Dysgenesis Research Articles

Chance diagnosis of mixed gonadal dysgenesis in an adult case of malignant gonadal germ cell tumor: a case report

BackgroundMixed gonadal dysgenesis (MGD) is a subtype of the disorders of sex development (DSD) associated with sex chromosome abnormalities characterized by abnormal external genitalia, short stature, and primary amenorrhea. This disease is generally diagnosed from the neonatal stage to early childhood, and by puberty at the latest. Cases that are phenotypically female or those with ambiguous genitalia experience a high risk of gonadal tumor formation. As tumor risk is known to increase with age, prophylactic bilateral gonadectomy is recommended following early diagnosis.Case presentationHere we report a case of an adult Japanese woman diagnosed with MGD during treatment for a giant pelvic tumor. The patient initially visited a gynecology clinic during puberty for primary amenorrhea, at which time an abnormality was found with the external genitalia. However, a diagnosis of MGD was not made at this time, resulting in the development of a malignant gonadal germ cell tumor in adulthood.ConclusionsFor early diagnosis of MGD and the prevention of gonadal tumor formation, it is essential that gynecologists fully understand MGD and other DSD.

The use of fluorescence in situ hybridization in the diagnosis of hidden mosaicism: apropos of three cases of sex chromosome anomalies

FISH has been used as a complement to classical cytogenetics in the detection of mosaicism in sex chromosome anomalies. The aim of this study is to describe three cases in which the final diagnosis could only be achieved by FISH. Case 1 was an 8-year-old 46,XY girl with normal female genitalia referred to our service because of short stature. FISH analysis of lymphocytes with probes for the X and Y centromeres identified a 45,X/46,X,idic(Y) constitution, and established the diagnosis of Turner syndrome. Case 2 was a 21-month-old 46,XY boy with genital ambiguity (penile hypospadias, right testis, and left streak gonad). FISH analysis of lymphocytes and buccal smear identified a 45,X/46,XY karyotype, leading to diagnosis of mixed gonadal dysgenesis. Case 3 was a 47,XYY 19-year-old boy with delayed neuromotor development, learning disabilities, psychological problems, tall stature, small testes, elevated gonadotropins, and azoospermia. FISH analysis of lymphocytes and buccal smear identified a 47,XYY/48,XXYY constitution. Cases 1 and 2 illustrate the phenotypic variability of the 45,X/46,XY mosaicism, and the importance of detection of the 45,X cell line for proper management and follow-up. In case 3, abnormal gonadal function could be explained by the 48,XXYY cell line. The use of FISH in clinical practice is particularly relevant when classical cytogenetic analysis yields normal or uncertain results in patients with features of sex chromosome aneuploidy.

An unusual case of ambiguous genitalia

Introduction: Mixed gonadal dysgenesis is most commonly associated with a mosaic 45X/46XY karyotype. The clinical phenotype may range from almost complete female or male external genitalia to ambiguous genitalia. The internal genitalia may be composed of dysgenetic testis on one side and a streak gonad on the contralateral side, however there can be varying configurations as well. The uterus and fallopian tubes are generally ipsilateral to the streak gonad and these retained Mullerian remnants are common. The presence of 45X may present with Turner like features including cardiac, renal anomalies and short stature. Case Report: We describe a case of ambiguous genitalia secondary to mixed gonadal dysgenesis where the sex assignment was made before the final diagnosis was reached. Conclusion: The diagnosis of mixed gonadal dysgenesis can be difficult for families. A multidisciplinary approach must be established for the patient and family while incorporating the psychosocial aspects also.

45,X/46,XY mosaicisme: Report of five cases and clinical review

Introduction The mosaicism 45, X/46, XY is a gonosomal abnormality characterized by a broad phenotypic spectrum, ranging from women with or without Turner syndrome stigmata, to men apparently normal, passing by the ambiguous phenotypes with variable virilisation of external genitalia. From the histological point of view, several situations may arise. Patients and methods We analyzed the clinical, hormonal, sonographic, and genitographics data, as well as peroperative and histological findings for five cases of mosaicism 45, X/46, XY, and we discussed treatment performed. Results The mean age of patients was 6.6 years, two had a female phenotype with clitoral hypertrophy (one of them had Turner syndrome stigmata), one had a normal male phenotype with bilateral cryptorchidism and two had an ambiguity of external genitalia assigned to male. Short stature was noted for four patients. Surgical exploration concluded to the diagnosis of mixed gonadal dysgenesis for four of our patients. No cases of gonadoblastoma have been reported, for girls a prophylactic gonadectomy was performed, for boys the streak gonad was resected and the dysgenetic testis biopsied and preserved, subject for constant monitoring. Conclusion This heterogeneity indicate the importance of an accurate clinical and histological evaluation of any patient presenting with 45, X/46,XY mosaicism.

Two cases of sex chromosomal mosaicism treated by laparoscopic gonadectomy

Two cases of sex chromosomal mosaicism treated by laparoscopic gonadectomy are described. Case 1 was a 23-year-old phenotypic female with primary amenorrhea. She had a history of a right inguinal herniorrhaphy at the age of 1 year and 3 months. Her external genitalia and vagina were normal, but chromosomal analysis showed mosaicism of 45X/46XY which comfirmed the diagnosis of mixed gonadal dysgenesis. A MRI demonstrated a small uterus and two high-intensity nodules near the orifice of both inguinal canals consistent with ectopic gonads. A laparoscopic bilateral gonadectomy was performed to avoid the risk of gonadoblastoma or dysgerminoma. The histopathologic study showed ovarian stromal cells lacking follicles and epithelial cells in the right gonad and a dysgenetic testis in the left nodule. Neither gonad contained neoplastic components. Case 2 was 28 years of age. She was diagnosed with Turner syndrome at the age of 2 years. Chromosomal analysis revealed a mosaic karyotype [45X/46X, idic(Y)]. Typical features of Turner syndrome, such as short statue, webbed neck, and a cubitus valgus deformity were observed. A MRI demonstrated a small uterus, but did not detect the location of the gonads. A laparoscopy was performed and streak gonads were identified adjacent to the oviducts bilaterally. Both gonads and oviducts were removed laparoscopically for prevention of neoplasm. The histopathologic examination revealed ovarian stromal cells without follicles and epithelial cells. Laparoscopy is helpful, not only to detect the location of gonads in patients with chromosomal abnormalities, but also to remove the structures with minimum invasion.

Limitations of G-banding Karyotype Analysis with Peripheral Lymphocytes in Diagnosing Mixed Gonadal Dysgenesis

Mixed gonadal dysgenesis (MGD) is an abnormal sexual differentiation syndrome usually presenting with ambiguous genitalia. Karyotype analysis is one of the essential components in the diagnosis of MGD and is conventionally done with peripheral lymphocytes by the G-banding technique. It is speculated that this conventional karyotype analysis has limitations since there are often difference in gonadal tissue analysis. Here we present four cases of MGD, in which karyotype analysis were performed by peripheral lymphocytes fluorescence in situ hybridization (FISH), gonad fibroblasts FISH and gonad fibroblasts G-banding technique, in addition to the conventional peripheral lymphocytes G-banding technique. In Case 1, the percentage of the 45,X cell line in lymphocytes decreased after birth and detection of mosaicism could only be done by karyotype of gonads at 7 mo of age. In Case 2, FISH analysis with peripheral lymphocytes was more useful for detecting low frequency mosaicism. In all cases, phenotype of gonads and external genitalia were more consistent with karyotype of gonads than that of the peripheral lymphocytes G-banding technique. In conclusion, conventional G-banding karyotype analysis with peripheral lymphocytes has limitations in the diagnosis and evaluation of MGD. Karyotype analysis by FISH or by using gonads is useful for diagnosing MGD and understanding of the phenotype of gonadal tissue.

GENITAL DUCT DEVELOPMENT ON STREAK GONAD SIDE IN FIFTEEN CHILDREN WITH 45, X AND Y-CONTAINING CHROMOSOME MOSAICISM

Genital duct development were studied in 15 children with 45,X and Y-containing chromosane mosaicism by laparotomy.Group 1:One patient showed bilateral intra-abdominal testes with an epididymis, a vas deferens, and a follopian tube. Group 2: Eight patients showed an unilateral scrotal testis and a contralateral streak gonad. On streak gonad side, an epididymis or vas deferens or both were found in 5 patients. Group 3: Four patients showed a unilateral intra-abdominal testis and a contralateral streak gonad. On the streak gonad side, a rudimentary vas deferens was found in 2 patients and a uterus were found in all 4 patients. Group 4: Two patients showed bilateral streak gonads associated with fallopian tube and a uterus. A rudimentary epididymis and vas deferens accompanied 1 out of 4 streak gonads. Twelve patients of Groups 2 and 3 were compatible with a diagnosis of mixed gonadal dysgenesis (MGD). Wolffian duct remnants accompanied 7 (58%) out of 12 streak gonads in 12 patients with MGD. and 8 (50%) out of 16 streak gonads in 14 patients of groups 2, 3 and 4.These findings indicated that the streak gonads in children with 45,X and Y-containing chromosome mosaicism frequently had functioning Leydig cells at least at the time of differentiation of the genital ducts, although none had properly functioning Sertoli cells at that time.

Genital Duct Development on Streak Gonad Side in Fifteen Children with 45, X and Y-containing Chromosome Mosaicism

Fifteen children with 45, X and Y-containing chromosome mosaicism were studied. Fourteen had unilateral or bilateral streak gonads. The remaining one patient had bilateral intra-abdominal testes. Development of genital ducts was studied by laparotomy.Group 1: One patient showed bilateral intra-abdominal testes accompanied by an epididymis, a was deferens, and a fallopian tube. Group 2: Eight patients showed an unilateral scrotal testis and a contralateral streak gonad. On the streak gonad side, an epididymis or was deferens or both were found in five, a uterus was found in seven and a fallopian tube was found in all eight patients. Group 3: Four patients showed a unilateral intra-abdominal testis and a contralateral streak gonad. On the streak gonad side, a was deferens was found in two patients and a fallopian tube and a uterus were found in all four patients. On the testis side, an epididymis and a was deferens were found in all four patients, although a fallopian tube was found in only one patient. Group 4: Two patients showed bilateral streak gonads associated with a fallopian tube and a uterus. A rudimentary epididymis and was deferens accompanied one out of four streak gonads of these two patients. Twelve patients of Group 2 and Group 3 were compatible with a diagnosis of mixed gonadal dysgenesis (MGD). Wolffian duct remnants accompanied seven (58%) out of 12 streak gonads in 12 patients with MGD, and eight (50%) out of 16 streak gonads in 14 patients of Group 2, Group 3, and Group 4.These findings indicated that the streak gonads in children with 45, X and Y-containing chromosome mosaicism frequently had functioning Leydig cells at least at the time of differentiation of the genital ducts, although none had properly functioning Sertoli cells at that time.