Dysgerminoma in a Prepubertal Girl with Complete 46XY Gonadal Dysgenesis: Case Report and Review of the Literature

BackgroundComplete 46XY gonadal dysgenesis (Swyer syndrome) is a rare and challenging diagnosis among prepubertal girls, as estrogen insufficiency becomes evident only during adolescence, with nonspecific symptoms such as primary amenorrhea and/or delayed puberty. Unfortunately, girls with Swyer syndrome are at high risk for malignancies in the dysgenetic gonads, which can be prevented only by performing prophylactic bilateral gonadectomy.CaseWe present a 9-year-old patient with Swyer syndrome diagnosed with dysgerminoma in the right gonad and gonadoblastoma in the left gonad after prophylactic bilateral gonadectomy.Summary and ConclusionConcerning the high risk of early gonadoblastoma and its malignant transformation, we recommend performing prophylactic bilateral gonadectomy at the time of diagnosis, even if the patient is prepubertal.     

Clinical and Reproductive Characteristics of Patients with Mixed Gonadal Dysgenesis (45,X/46, XY)

IntroductionMixed gonadal dysgenesis (MGD) or 45,X/46,XY mosaicism is a sex chromosomal disorder of sexual development. We aim to characterize the clinical and reproductive features of 45X/46 XY attending tertiary care center in Kerala.Materials and MethodRetrospective review of clinical records which include clinical presentation, hormonal profile, cytogenetics, psychosexual assessment, and histopathology of gonadectomy specimen of ten cases of 45X/46 XY mosaicism who attended Endocrinology/ OBG out patient department from 2008 to 2020.ResultsThe mean ages of all the cases were 12 ± 3.79 years (± 2 SD). Short stature was universally seen. Virilisation was the most common manifestation (80%) followed by delayed puberty (20%). Autoimmune thyroid disease was seen in 40% of cases. We noticed a delayed presentation in our clinical study. 45X/46 XY subjects who wished to continue as female underwent gonadectomy and were feminized with hormone replacement therapy. Male 45X/46 XY who retained their undescended testis is planned for periodic surveillance for malignancy.Conclusion45X/46 XY may present like Turner’s syndrome in clinical practice. Early counseling and gender assignment by a panel of specialists are crucial. Delayed presentation is less commonly encountered now a day and may pose a clinical challenge. Management in 45X/46 XY is multi-disciplinary which includes Turner’s like surveillance, proper sex assignment, timely genital reconstruction surgeries, gonadectomy, gonadal monitoring, and hormonal replacement therapy is needed.     

Successful pregnancy in a patient with a 46,XY karyotype

OBJECTIVE: To report a case of successful pregnancy in a patient with 46,XY karyotype with primary ovarian failure. DESIGN: Case report. SETTING: Fertility Research Center, G.G. Hospital, Chennai, Tamil Nadu, India. PATIENT(S): A 27-year-old woman with hypoplastic uterus, normal fallopian tubes on both sides, and gonadal dysgenesis. INTERVENTION(S): Chromosomal analysis, diagnostic laparoscopy, donor oocyte program, gamete intrafallopian transfer, and gonadectomy. MAIN OUTCOME MEASURE(S): Response to hormone replacement therapy and the probability of achieving a pregnancy by a tubal procedure. RESULT(S): Treatment was successful, and the patient delivered a live baby. CONCLUSION(S): A hypoplastic uterus of patients with the 46,XY karyotype can be stimulated by the use of cyclical steroid therapy to accommodate pregnancy and facilitate tubal procedures in patients with normal fallopian tubes.     

性腺发育异常的女性生殖道畸形诊治

性腺发育异常疾病亚型多,临床表现各异,部分患者有女性外生殖器男性化表现,早期明确诊断,适时手术非常重要。女性外生殖器畸形的女性化矫形手术主要有阴蒂整形术、阴唇整形术、阴道成形术,手术方法和手术时机的选择需个体化。含有Y染色体的患者和睾丸位置异常的患者易于发生性腺性母细胞瘤和生殖细胞肿瘤,应行性腺切除术。     

Mutation analysis of the SRY,NR5A1, and DHH genes in six Chinese 46,XY women

Objective.?To determine the genetic cause of 46,XY sex reversal in six Chinese women.

Methods.?G-banded karyotyping and mutation analysis of the SRY, NR5A1, and DHH genes using direct sequencing were performed in six Chinese women aged from 15- to 23-year old with poor sexual development and primary amenorrhea. Clinical, endocrinologic, and ultrasonographic evaluation was reported.

Results.?Three novel mutations, two heterozygous point mutations in SRY, and one heterozygous microdeletion in NR5A1 were found to be causative in three of the patients.

Conclusion.?This helps pathogenic study and provides new information for genetic counseling of 46,XY sex reversals.     

女性表型46,XY性发育障碍的临床、病理特征及遗传学检测

目的:总结女性表型的46,XY性发育障碍患者的临床及病理学特点,对其进行鉴别诊断及遗传学检测,为类似病例的诊断和鉴别诊断提供借鉴资料。方法:回顾分析2010年至2015年在深圳市妇幼保健院行妇科手术的3例46,XY性发育障碍患者的临床资料。将切除的性腺组织进行病理学诊断;提取患者及家属基因组DNA,应用Sanger测序、二代测序方法、MLPA、染色体基因组芯片分析等方法进行遗传学检测以寻找致病基因变异。结果:1例患者为完全型雄激素不敏感综合征(CAIS),病理结果证实一侧隐睾见精原细胞瘤,其AR基因第7外显子检测到移码突变c.2546_2547 insA(p.N849K,fs X32),此突变为已报道导致CAIS的突变方式;1例患者临床诊断为单纯性腺发育不良,性腺病理结果为不成熟的卵巢组织,患者SRY基因的HMG区域检测到c.206TC(p.V69A)突变,此突变未见报道;1例患者临床诊断为单纯性腺发育不良,病理结果为双侧性腺母细胞瘤伴无性细胞瘤,性发育相关基因未检测到明确的致病突变。结论:综合利用多种检测方法对女性表型46,XY性发育障碍患者进行致病基因检测,其中2例患者分别由AR基因、SRY基因突变引起,其中SRY基因c.206TC(p.V69A)为新发现的突变。     

High-level mosaicism for 45,X in 45,X/46, XY at amniocentesis in a pregnancy with a favorable fetal outcome and cytogenetic discrepancy in various tissues

ObjectiveWe present prenatal diagnosis of high-level mosaicism for 45,X by amniocentesis in a pregnancy with a favorable fetal outcome.Case reportA 35-year-old, gravida 2, para 1, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 45,X[13]/46,XY[11]. Simultaneous array comparative genomic hybridization (aCGH) on uncultured amniocytes revealed the result of Yp11.3q11.21 × 0–1 [0.1], Yq11.21q11.23 × 0–1 [0.6]. At 19 weeks of gestation, she underwent the second amniocentesis which revealed a karyotype of 45,X[13]/46,XY[12], and aCGH and multiplex ligation-dependent probe amplification (MLPA) on uncultured amniocytes showed 37% mosaicism for Y-deleted cells. At 28 weeks of gestation, she underwent the third amniocentesis which revealed a karyotype of 45,X[25]/46,XY[25], and aCGH on uncultured amniocytes revealed the result of Yq11.21q11.23 × 0.5, Yq11.23q12 × 0.7. Interphase fluorescence in situ hybridization (FISH) analysis on uncultured amniocytes revealed that 16.67% (20/120 cells) were Y-deleted cells. The parental karyortypes and prenatal ultrasound were normal. At 37 weeks of gestation, a 2707-g phenotypically normal male baby was delivered with normal male external genitalia. The karyotypes of cord blood, umbilical cord and placenta were 45,X[25]/46,XY[15], 45,X[18]/46,XY[22] and 45,X[25]/46,XY[15], respectively. When follow-up at age five months, the neonate was normal in external genitalia and physical development. The peripheral blood had a karyotype of 45,X[29]/46,XY[11], and FISH analysis on 100 buccal mucosal cells showed no abnormal signals. When follow-up at age 11 months, the neonate was physically normal, and the peripheral blood had a karyotype of 45,X[17]/46,XY[23].ConclusionHigh-level mosaicism for 45,X in 45,X/46, XY at amniocentesis can be associated with a favorable fetal outcome despite the presence of cytogenetic discrepancy in various tissues.     

Detection of mosaicism for 46,X,i(Y) (q10) in the blood lymphocytes in a phenotypically normal male neonate with prenatally detected 45,X/46, XY at amniocentesis and cytogenetic discrepancy in various tissues

ObjectiveWe present detection of mosaicism for 46,X,i(Y) (q10) in the blood lymphocytes in a phenotypically normal male neonate with prenatally detected 45,X/46, XY at amniocentesis and cytogenetic discrepancy in various tissues.Case reportA 35-year-old, gravida 2, para 1, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 45,X [8]/46,XY [15]. Simultaneous array comparative genomic hybridization (aCGH) on uncultured amniocytes revealed the result of arr (Y) × 0–1 with 25.493-Mb mosaic deletion of chromosome Yp11.31-q11.23. Prenatal ultrasound findings were unremarkable. The fetus had normal male external genitalia on fetal ultrasound. Following genetic counseling, the pregnancy was carried to 38 weeks of gestation, and a phenotypically normal male baby was delivered without any abnormalities of the male external genitalia. The cord blood had a karyotypes of 46,X,i(Y) (q10)[8]/45,X[3]/46,XY [29], and placenta had a karyotypes of 45,X [25]/46,X,i(Y) (q10)[7]/46,XY [8]. When follow-up at age two months, the neonate was normal in development. The peripheral blood had a karyotypes of 46,X,i(Y) (q10)[8]/45,X[5]/46,XY [27]. Interphase fluorescence in situ hybridization (FISH) analysis on 101 buccal mucosal cells showed normal X and Y signals in 101/101 cells.ConclusionFetuses with 45,X/46, XY at amniocentesis can be associated with mosaicism for 46,X,i(Y) (q10) in the blood lymphocytes, cytogenetic discrepancy in various tissues and a favorable outcome.     

Adnexal Torsion Due to Borderline Mucinous Tumor of the Gonad in a Prepubertal Girl with Mixed Gonadal Dysgenesis (45,X/46,XY) and a Turner Phenotype

BackgroundTurner syndrome (TS) is a sex chromosome condition characterized by complete or partial loss of the X chromosome. Patients with mixed gonadal dysgenesis (45,X/46,XY) and a Turner phenotype are predisposed to gonadoblastoma with malignant transformation.CaseWe present the case of a TS patient with 45,X/46,XY with 2 episodes of left adnexal torsion (AT). Biopsies during detorsion showed benign mucinous cystadenoma. Pathology following bilateral gonadectomy revealed a left gonad with mucinous borderline tumor and right gonad with gonadoblastoma, both of which have malignant potential.Summary and ConclusionGonadectomy is recommended in XY gonadal dysgenesis to decrease risk of malignant transformation from gonadoblastoma. Although rare in pediatric patients, ovarian malignancies have been identified among AT cases. To our knowledge, we present the first case of AT due to borderline ovarian mucinous tumor of the ovary and contralateral gonadoblastoma in a patient with mixed gonadal dysgenesis (45,X/46,XY) and a Turner phenotype.