|Year : 2019 | Volume
| Issue : 2 | Page : 169-172
A case of mixed gonadal dysgensis: A diagnostic challenge
Uma Kaimal Saikia1, Dipti Sarma1, Darvin Vamadevan Das1, JK Goswami2, Kaushik2, Chandan Saikia3, Abilash Nair4
1 Department of Endocrinology, Gauhati Medical College, Guwahati, Assam, India
2 Department of Pediatric Surgery, Gauhati Medical College, Guwahati, Assam, India
3 Department of Pathology, Gauhati Medical College, Guwahati, Assam, India
4 Department of Endocrinology, Govt Medical College, Trivandrum, Kerala, India
|Date of Web Publication||17-Jun-2019|
Dr. Darvin Vamadevan Das
Department of Endocrinology, Gauhati Medical College, Guwahati, Assam
Source of Support: None, Conflict of Interest: None
| Abstract|| |
A 2-year-old child reared as a girl child was brought by parents with ambiguous genitalia noticed since birth. There was no history of failure to thrive or salt-losing crisis. On examination, the child had normal height and weight with normal blood pressure and no dysmorphism or Turners stigmata with external genitalia Prader Score 2. Ultrasound of the pelvis revealed hypoplastic uterus with no gonads visualized. There was no evidence of hypocortisolemia (8 am cortisol 14.08 mcg/dl) or elevated level of 17-OH-progesterone (1.1 ng/mL). Pooled follicle-stimulating hormone and luteinizing hormone levels were 2.66 mIU/ml and 0.1 mIU/ml, respectively, thyroid-stimulating hormone: 2.36 mIU/L, T4: 134.5 nmol/L, total testosterone: 2.5 ng/dl. Posthuman chorionic gonadotropin stimulation showed total testosterone levels 267 ng/dL, dihydrotestosterone: 155 pg/mL, androstenedione: 0.3 ng/mL indicating functioning testicular tissue without any evidence of 17-beta hydroxylase or 5-alpha reductase deficiency. Karyotyping revealed 45, XO genotype on two separate occasions. In view of the discrepancy between karyotype finding and ultrasound reports with the clinical and hormonal picture, fluorescence in situ hybridization cytogenetic study was carried out and showed MONOSOMY X (90% cells)/SEX ANEUPLOIDY XYY (10% cells). Laparoscopic examination showed gonad in the right ovarian fossa and left streak gonad with bilateral fallopian tubes and hypoplastic uterus. Genitoscopy showed normal vagina and cervix. Cystoscopy showed normal urethra and urinary bladder. Biopsy was taken from both gonads. A thorough histopathological examination of this specimen showed the structure of seminiferous tubules with Leydig cells in the right gonad with streak ovary on the left side. The child underwent bilateral gonadectomy and rehabilitated her to lead a life as a girl.
Keywords: 45X/47 XYY, disorders of sexual differentiation, mixed gonadal dysgenesis
|How to cite this article:|
Saikia UK, Sarma D, Das DV, Goswami J K, Kaushik, Saikia C, Nair A. A case of mixed gonadal dysgensis: A diagnostic challenge. J Hum Reprod Sci 2019;12:169-72
|How to cite this URL:|
Saikia UK, Sarma D, Das DV, Goswami J K, Kaushik, Saikia C, Nair A. A case of mixed gonadal dysgensis: A diagnostic challenge. J Hum Reprod Sci [serial online] 2019 [cited 2021 Sep 19];12:169-72. Available from: https://www.jhrsonline.org/text.asp?2019/12/2/169/260490
| Introduction|| |
Mixed gonadal dysgenesis (MGD) is a rare disorder of sexual differentiation which occurs due to asymmetrical gonadal development. We herein report an interesting case of MGD who presented clinically as ambiguous genitalia with nonpalpable gonads with a rare karyotype of 45X/47 XYY.
| Case Report|| |
We present a case of a 2-year-old child brought by parents with ambiguous genitalia noticed since birth. Child born at term to a nonconsanguineous parents. No history of maternal virilization, drug intake during pregnancy, history of salt-wasting crisis or any similar illness running in the family. The child was assigned female sex for rearing and had normal developmental milestone till the date of presentation. On examination, the child had a height of 92 cm (at the 75th centile for age) and weight of 12 kg (at the 75th centile for age) with normal blood pressure and no dysmorphism or Turner's stigmata. External genitalia [Figure 1] showed ambiguity in the form of a phallus of 4 cm with partially fused rugosed labioscrotal folds, perineal urethral opening, vaginal opening, and nonpalpable gonads. Systemic examination was within the normal limit.
Laboratory investigations showed normal hemoglobin, blood glucose, serum electrolytes, and normal cortisol reserves (8 am cortisol 14.08 mcg/dl) with normal 17-OH-progesterone (1.1 ng/ml). Pooled follicle-stimulating hormone and luteinizing hormone levels were 2.66 mIU/mL and 0.1 mIU/mL, respectively, thyroid-stimulating hormone: 2.36 mIU/L, T4: 134.5 nmol/L, and basal total testosterone: 2.5 ng/dL. Posthuman chorionic gonadotropin (hCG) stimulation revealed a several-fold elevation of serum total testosterone levels (267 ng/dl), dihydrotestosterone value of 155 pg/ml, and androstenedione of 0.3 ng/mL indicating functioning testicular tissue. Ultrasound of the pelvis revealed a hypoplastic uterus with no gonads visualized. Karyotyping revealed 45, XO genotype in two separate occasions. In view of virilization of external genitalia which is not seen in a pure XO karyotype, we proceeded to do fluorescence in situ hybridization (FISH) for the identification of Y chromosome [Figure 2].
Laparoscopic examination was done to visualize the gonads and ducts. Genitoscopy showed normal vagina and cervix. Cystoscopy showed normal urinary bladder and urethral orifice. Laparoscopy showed bilateral gonads in the ovarian fossa with bilateral Fallopian tube More Detailss [Figure 3] and [Figure 4]. The left gonad was grossly suggestive of streak gonad [Figure 4]. Furthermore, hypoplastic uterus was visualized. A thorough histopathological examination of the right gonad showed structure of seminiferous tubules and Leydig cells suggestive of the testis [Figure 5]. No ovarian tissue noted in these sections. Left gonad showed streak ovary as evident by a single primordial follicle and abundant stroma [Figure 6].
| Discussion|| |
This 2-year-old normotensive child reared as a girl on clinical examination revealed ambiguous genitals with nonpalpable gonads with normal anthropometry, no hyperpigmentation, dysmorphism, or Turner's stigmata. Congenital adrenal hyperplasia was ruled out clinically and biochemically. Ultrasound showed hypoplastic uterus and nonvisualization of gonads. Karyotyping sent in two separate occasions showed 45X genotype. Subsequently, hCG stimulation was done and demonstrated the presence of testicular tissue as evident by several-fold elevation of post-hCG total testosterone levels. At this point, we were left with the possibility of partial androgen insensitivity syndrome (PAIS), ovotesticular DSD (OT-DSD), MGD, or aromatase deficiency, respectively. The presence of the uterus and absence of maternal virilization at pregnancy ruled out the possibility of PAIS and aromatase deficiency. It is already known that Turner's syndrome never presents with ambiguous genitals, although the karyotype was of Turner's. In view of discrepancy between the biochemical results, ultrasound finding and karyotyping as suggested by high-stimulated testosterone levels, the presence of hypoplastic uterus, and Turner's karyotype, we decided to do FISH to detect the presence of Y chromosome or mosaic karyotype. FISH cytogenetics revealed the presence of two Y chromosomes and one X chromosome in 10% of the lymphocytes studied. Remaining 90% lymphocytic cells showed 45X karyotype (monosomy X). The karyotype was suggestive of MGD. Although 45X/46XY is the most common karyotype in patients with MGD, rare mosaic karyotype like 45X/47XYY or 45X/46XY/47XYY is also found in such patients. MGD represents an intermediate between pure gonadal dysgenesis and OT-DSD. The external genitalia, internal genitalia, and gonadal phenotype are highly variable. After ascertaining the karyotype and hormonal profile, we decided to demonstrate internal ducts and gonad by the laparoscopy. It is worth mentioning the reason for laparoscopy here. We did a magnetic resonance imaging of the pelvis which did not give any added information regarding internal gonads or duct. The report was only suggestive of probable rudimentary uterus which the radiologist could not give a definite opinion. Considering the inconclusive evidence from imaging, we went for a gold standard laparoscopic procedure. Genitoscopy showed normal vagina and cervix. Laparoscopy showed bilateral gonads with fallopian tubes and hypoplastic uterus. The left gonad was grossly suggestive of streak gonad. Histopathology of the gonads demonstrated right testis and left streak ovary. In MGD, the gonadal phenotype ranges from streak gonads through dysgenetic to functioning testes. Usually, a functioning testis one side with streak testis or very rarely ovarian-like stroma and sparse primordial follicles may be seen on the other side. OT-DSD is close differential. The karyotyping and absence of ovarian follicles on either side ruled out OT-DSD.
In this case report, we would like to highlight the approach to clinical, biochemical, and genetic discrepant reports in DSD. At times when karyotyping does not yield a specific diagnosis, we need to depend on higher cytogenetics as illustrated here. Standard karyotyping studies chromosomal pattern in 20–30 cells during metaphase division. In FISH analysis, the cells are studied in 100 cells at interphase and specific probes are used to detect the X and Y chromosomes which yields better results than standard karyotyping. We also present a rare mosaic karyotype (45X/47XYY) and rare histopathology (functioning testis in one side with streak ovary on other side) of MGD. As mentioned earlier, streak ovary is usually a rare histology in MGD. The presence of Y chromosome in dysgenetic gonad renders the child at high risk to gonadal malignancy (gonadoblastoma). Considering the same and also the parents desire to raise the child, as a girl bilateral gonadectomy was done after explaining the consequences to the parents and future need for hormone replacement therapy at the puberty. The presence of Turner karyotype in 90% cells indicates Turner syndrome complication surveillance at periodicity. As it is known, Turner syndrome per se is considered as a chromosomal disorder of growth failure and primary amenorrhea, it is prudent to monitor for height velocity in these subset of patients at regular interval. Growth hormone therapy is indicated when growth failure is appreciated while on surveillance. Our aim is to monitor for height velocity at 6-month interval anticipating the possibility of growth failure due to the presence of Turner's karyotype and later sex hormonal therapy to induce puberty. Clitoroplasty is being planned.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]