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.     

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.     

Pure yolk sac tumor of the ovary with mosaic 45X/46X+mar Turner's syndrome with a Y-chromosomal fragment

A pure yolk sac tumor (endodermal sinus tumor) of the dysgenetic gonad developed in a 23-year-old woman whose karyotype was mosaic 45 X/46X+mar Turner's syndrome is reported. Molecular biological studies showed that the patient's DNA contained a fragment of Y chromosome. This case seems to be extremely rare case of developing a pure yolk sac tumor in a patient with mosaic Turner syndrome with a Y-chromosomal fragment. Received: 5 September 1997 / Accepted: 9 December 1997     

Laparoscopic gonadectomy in a case of a dicentric fluorescent Y-chromosome mosaicism with Turner-like phenotype and virilized external genitalia

In few cases of Turner syndrome the karyotype reveals the presence of an additional Y-bearing cell line, which is referred to as a borderline case of mixed gonadal dysgenesis. We report a 20-year-old woman with primary amenorrhea, virilization and a few Turner stigmata, who revealed rare mosaicism of 45,X/46,X dic (Y; 5)(q12; q11), +5/46,X, der (Y), which was detected by conventional G-banding and multicolor spectral karyotyping. She underwent laparoscopic gonadectomy in which mixed gonadal dysgenesis was found and both gonads were removed. No evidence of gonadoblastoma was noted on the gonads. Virilization improved postoperatively. We recommend gonadectomy via laparoscope in women presenting with Turner-like phenotype, virilization and the presence of a Y chromosome. This report describes the role of cytogenetic and molecular genetic investigations in the definition of mosaicism in Turner syndrome.     

Turner Syndrome with Y Chromosome: Spontaneous Thelarche,Menarche, and Risk of Malignancy

Study ObjectiveGirls with Turner syndrome with Y-chromosome material (TS + Y) are assumed to have nonfunctional gonads with increased tumor risk, therefore prophylactic gonadectomy is recommended at diagnosis. In this study we aimed to determine rates of spontaneous thelarche (ST) and spontaneous menarche (SM), and prevalence of gonadal tumor and malignancy in girls with TS + Y, to further inform discussions about gonadectomy.DesignRetrospective review of clinical and pathology data.SettingMulticenter study involving 4 United States children's hospitals.ParticipantsPatients included those with a genetically proven diagnosis of TS + Y and phenotypically female genitourinary exam.InterventionsDemographic characteristics, pubertal development, and gonadal pathology data were abstracted from clinical records. Data for ST were analyzed for patients aged 13 years and older and SM for patients older than 15 years.Main Outcome MeasuresST, SM, prevalence of gonadal tumor, and malignancy.ResultsForty-four patients met inclusion criteria. Nineteen patients were 13 years or older; 8/19 (42%) had ST and reached Tanner stages 2-4 and 2 (11%) had normal ovarian pathology. Nineteen patients were 15 years or older; 2/19 (11%) had SM. Thirty-seven patients underwent gonadectomy; 35 had available pathology results. Gonadoblastoma was identified in 35/7 patients (19%), 1 in situ germ cell neoplasia, and 1 dysgerminoma (3%). One patient with bilateral gonadoblastoma had ST and SM.ConclusionIn this multicenter cohort, 42% of girls with TS + Y entered puberty spontaneously and 11% had SM, supportive of gonadal function. Risk of tumor was similar to previous reports. To achieve informed decision-making, discussions about gonadectomy should incorporate potential for gonadal function and tumor risk.     

Maternal XX/X chromosome mosaicism in donor oocyte in vitro fertilization (IVF)

ObjectiveTo evaluate if the degree of maternal X chromosome mosaicism is correlated to the pregnancy loss rate in donor oocyte IVF in women with a Turner syndrome mosaic (TS-Mosaic) diagnosis.DesignProspective trial.Patients and methodsWomen with X chromosome Turner syndrome mosaicism and infertility were enrolled in a clinical trial. The rate of mosaicism was determined through florescence in situ hybridization (FISH) of 500 maternal lymphocytes. Following a detailed medical, including cardiac, evaluation, donor oocyte in vitro fertilization (IFV) was performed and pregnancy and pregnancy loss rates were observed.ResultsThe rates of maternal X chromosome mosaicism noted in the cycles from women with miscarriages (3%, 4%, 4%, and 6%) were not statistically different from cycles in TS-Mosaic women with normal deliveries (3% and 11%). These data suggest that the rate of maternal X chromosome mosaicism does not affect pregnancy loss rates in TS-Mosaic women undergoing donor oocyte IVF.     

Morphology of the genitals in gonadal dysgenesis

The entity includes the Turner syndrome, the pure gonadal dysgenesis (Swyer syndrome), the asymmetrical gonadal differentiation, and gonadal dysgenesis of some forms of trisomy. The necessity of prophylactic gonadectomy in all patients with Y chromosome is stressed because of a close association with the arising of tumors in the dysgenetic gonads. The requirements are described of a successful substitution with steroids.     

Reproductive outcomes after preimplantation genetic testing in mosaic Turner syndrome: a retrospective cohort study of 100 cycles

PurposeThe purpose of this study is to explore the reproductive outcomes of women with Turner syndrome (TS) in preimplantation genetic testing (PGT) cycles.MethodsA retrospective study of 100 controlled ovarian stimulating cycles, 68 TS (sixty-four mosaic Turner syndrome (MTS) and four pure Turner syndrome (PTS)) women underwent PGT was conducted from 2013 to 2018.ResultsEmbryo X chromosome abnormal rates of TS women were significantly higher than women with normal karyotype (7.04 vs 1.61%, P<0.01). Cumulative live birth rates (CLBR) after PGT-NGS treatment were lower in TS than control (31.15 vs 45.59%, P<0.05). Clinical pregnancy rates per transfer (CPR), miscarriage rates (MR) and live birth rates per transfer (LBR) remained comparable between TS and control group. Reproductive outcomes (X chromosome abnormal rates, CPR, MR, LBR and CLBR) among low (<10%), medium (10–50%) and high (>50%) level 45,X mosaicism groups were not statistically different.ConclusionsTo avoid high risk of embryo X chromosome abnormalities, prenatal or preimplantation genetic testing should be recommended to mosaic or pure TS patients.     

Anomalies de structure du chromosome Y et syndrome de Turner

Although specifically male, the human Y chromosome may be observed in female karyotypes, mostly in women with Turner syndrome stigmata. In women with isolated gonadal dysgenesis but otherwise normal stature, the testis determining factor or SRY gene may have been removed from the Y chromosome or may be mutated. In other women with Turner syndrome, the karyotype is usually abnormal and shows a frequent 45,X/46,XY mosaicism. In these cases, the phenotype depends on the ratio between Y positive and 45,X cell lines in the body. When in mosaicism, Y chromosomes are likely to carry structural abnormalities which explain mitotic instability, such as the existence of two centromeres. Dicentric Y isochromosomes for the short arm (idic[Yp]) or ring Y chromosomes (r[Y]) are the most frequent abnormal Y chromosomes found in infertile patients and in Turner syndrome in mosaic with 45,X cells. Although monocentric, deleted Y chromosomes for the long arm and those carrying microdeletions in the AZF region are also instable and are frequently associated with a 45,X cell line. Management of infertile patients carrying such abnormal Y chromosomes must take into account the risk and the consequences of a mosaicism in the offspring.     

Mucinous cystadenoma in a female patient with 45,X/46,XY karyotype

The mosaic karyotype of 45,X/46,XY has a wide phenotypic spectrum and there are substantial differences between prenatally and postnatally diagnosed cases. The phenotype varies between normal male to classical Turner syndrome. There is a high risk of gonadal tumor development in the dysgenetic gonads of patients with sex chromosome mosaicism. We report a case of a 24-year-old patient with a pelvic mass and amenorrhea referred to our laboratory for karyotyping. Peripheral blood chromosome analysis showed a mosaic karyotype of 45,X[17]/46,XY[83]. The tumor originated from the left ovary and the right ovary was found to be a streak gonad. The uterus was intact. Pathologic examination of the tumor revealed mucinous cystadenoma. Physical examination of the patient showed signs of Turner syndrome, as short stature (145 cm), short neck and asymmetric shoulders. Her mental state was normal. Y chromosome microdeletion screening involving SRY and ZFY genes was performed and no deletion was found. The patient was informed about the condition during the genetic counseling session.     

Turner综合征患者标记染色体的鉴定与分析

目的 分析11例携带标记染色体的Turner综合征患者的核型,研究这类染色体的表型效应。方法 选择11例具Turner综合征表型的患者,常规核型分析均显示为携带标记染色体的嵌合体,其中6例标记染色体呈环状。患者G带核型表示为mos．45,X／46,X,＋mar或者mos．45,X／46,X,＋r．以X／Y着丝粒探针,应用荧光原位杂交（FISH）技术分析这些标记染色体起源,对其中2例较大的环状染色体,结合反向染色体涂染确定断裂位点,比较不同断裂位点的标记染色体的遗传学效应。结果11例患者所携带的标记染色体均为环状染色体,r（X）的断裂位点分别位于Xp22、Xq22、Xq24、Xq26等。结论 Turner综合征患者的标记染色体主要来源于X染色体,且表现为r（X）形式。r（X）均以嵌合型的形式存在。     

Swyer Syndrome: A Case of Dysgerminoma Solely within the Fallopian Tube

Background46XY pure gonadal dysgenesis (Swyer syndrome) is a rare disorder of sexual development. Patients have a 46XY karyotype, though phenotypically they appear female with normal external genitalia and vagina. Although patients exhibit normal Müllerian structures (uterus, fallopian tubes, and vagina), they possess a pair of bilateral undifferentiated gonad streaks. Delayed puberty and primary amenorrhea are the common presentations. There is an increased risk of developing tumors in the gonads and therefore a bilateral gonadectomy is recommended.CaseA 16-year-old girl who presented with primary amenorrhea was diagnosed with Swyer syndrome. She underwent prophylactic bilateral gonadectomy and salpingectomies. She was discovered to have no gonadal malignancy, conversely dysgerminoma solely within the fallopian tube.Summary and ConclusionBoth bilateral salpingectomies and bilateral gonadectomies should be recommended as the operation of choice in patients with Swyer Syndrome.     

Prenatal diagnosis of 45,X and 45,X mosaicism: the need for thorough cytogenetic and clinical evaluations

OBJECTIVES: Mosaicism involving a 45,X cell line is relatively common in prenatal diagnosis. In prenatally diagnosed cases, the prognosis of non-mosaic 45,X and 45,X/46,XY mosaicism are different. Therefore, accurate identification of a cell line containing Y chromosome is critical for genetic counseling and postnatal management. METHODS: We investigated the ultrasound findings and outcomes of pregnancies with a 45,X cell line identified during mid-trimester cytogenetic analysis. RESULTS: A total of 105 cases were found to have a 45,X cell line by standard cytogenetic analysis. Seventy-four cases were found to have non-mosaic 45,X at initial diagnosis. Of these 74 cases, 68 had abnormal ultrasound findings that were characteristic of Turner syndrome. Of the six cases with normal ultrasound findings, ultrasound examination was normal with male genitalia identified in three cases. Thorough cytogenetic and fluorescent in situ hybridization (FISH) analysis identified Y chromosome material in all three cases, one with a dicentric Y;14 chromosome and the other two cases with a marker chromosome containing Sex-determining Region (SRY) material in a small portion of the cells. In contrast, in 31 cases with a mosaic 45,X karyotype, ultrasound abnormality was identified only in one case. CONCLUSIONS: The present data suggest the need for follow-up ultrasound examination and thorough cytogenetic and molecular analysis for Y chromosome material in 45,X cases with normal ultrasound findings.     

Analysis of Spermatozoa from Seven ICSI Males with Constitutional Sex Chromosomal Abnormalities by Fluorescent In Situ Hybridization

Purpose: The objective was to estimate the risk for subfertilemales with a constitutional sex chromosomal abnormalityof transmitting such a chromosome abnormality to theirchildren, conceived by intracytoplasmic sperm injection(ICSI). Methods: Semen samples were obtained from seven severelyoligospermic ICSI candidates. Six of them had a numericalsex chromosomal abnormality, including mosaic 45,X/46,XY,mosaic 46,XY/47, XXY, 47,XXY (Klinefelter's syndrome), and47,XYY. One male had a structural abnormality, namely, aninversion of the Y chromosome. The semen was studied bythree-color fluorescent in situ hybridization (FISH) withprobes specific for chromosomes 18,X, and Y. Results: Chromosomal aneuploidy rates of any of the threechromosomes were significantly higher than the aneuploidyrates observed in three control samples but comparable tothe rates observed in 10 ICSI candidates witholigoasthenoteratozoospermia (OAT) and a normal constitutionalkaryotype. Conclusions: Our data indicate that males with (mosaic) sexchromosomal abnormalities have no higher risk of producingoffspring with a sex chromosomal abnormality by ICSI thanOAT males with a normal karyotype.     

Mosaic 45,X/46, XX at amniocentesis with high-level mosaicism for 45,X in a pregnancy with a favorable fetal outcome and postnatal decrease of the 45,X cell line

ObjectiveWe present mosaic 45,X/46, XX at amniocentesis with high-level mosaicism for 45,X in a pregnancy with a favorable fetal outcome and postnatal decrease of the 45,X cell line.Case reportA 20-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of the non-invasive prenatal testing (NIPT) result of −4.82 Z score in sex chromosome at 12 weeks of gestation suggestive of Turner syndrome in the fetus. Amniocentesis revealed a karyotype of 45,X [18]/46,XX [15], and simultaneous multiplex ligation-dependent probe amplification (MLPA) on the DNA extracted from uncultured amniocytes showed mosaic Turner syndrome. Prenatal ultrasound and parental karyotypes were normal. She was referred for genetic counseling at 24 weeks of gestation, and continuing pregnancy was encouraged. At 39 weeks of gestation, a 2550-g phenotypically normal female baby was delivered. The karyotypes of cord blood, umbilical cord and placenta were 45,X [24]/46,XX [16], 45,X [23]/46,XX [17] and 45,X [28]/46,X,del(X) (q23)[12], respectively. When follow-up at age two months, the neonate was phenotypically normal in development. The peripheral blood had a karyotypes of 45,X [16]/46,XX [24]. Interphase fluorescence in situ hybridization (FISH) analysis on 103 buccal mucosal cells showed normal disomy X signals in all cells.ConclusionHigh-level mosaicism for 45,X in 45,X/46, XX at amniocentesis can be associated with a favorable fetal outcome, cytogenetic discrepancy in various tissues, and postnatal decrease of the 45,X cell line.     

Y-specific sequences in Turner syndrome]

Turner Syndrome (TS) is the only one monosomy that occurrs+ in humans. The cytogenetics of TS is very well known from years. It has been estimated that almost 98-99% of TS foetuses end in abortion. It was suggested that the monosomy arises relatively late during embryonal development and survived TS individuals could be mosaics. It has been proved that mosaic karyotype mos 45,X/46X, + mar(Y) occurrs++ in 2% to 11% of TS patients. The patients having additional cell line containing der(Y) are at increased risk of gonadoblastoma development. In these cases gonadectomy should be considered. Therefore detection of mosaic and establishing the origin of marker chromosome (specially containing Y-specific sequences) is of special importance. The aim of present study was to detect the small mosaics, containing mar(Y) in TS patients, by using PCR and FISH techniques. Eight Y sequences for the PCR analyses as well as bicolor in situ hybridisation with painting probes for Y and X chromosomes have been applied. The positive amplification for Y-specific sequences has been detected in 7% of TS patients. Our results support the thesis that searching for the Y sequences should be introduced to routine genetic TS diagnosis.     

Polycystic Ovary Syndrome and Incidental Diagnosis of Mosaic Turner Syndrome

BackgroundPolycystic ovary syndrome (PCOS) is a common condition in women of reproductive age. Mosaic Turner syndrome (TS) is a genetic disorder with significant phenotypic variability. The occurrence of PCOS in women with mosaic TS has been infrequently studied.CaseA 30-year-old nulligravid woman presented with oligomenorrhea, hyperandrogenism, infertility, and ultrasound polycystic ovary morphology. She was diagnosed with PCOS and conceived following ovulation induction. After 2 inconclusive non-invasive prenatal screening results, she was referred to medical genetics. A maternal karyotype resulted in a diagnosis of 45,X/46,XX mosaic TS. She delivered a healthy 46,XY infant at term.ConclusionPCOS can affect women with mosaic TS. Further studies are needed to better characterize the reproductive profile of women with mosaic TS, including the presentation of concurrent PCOS.     

The effects of estrogen induction therapy on pubertal presentations in turner syndrome patients

ObjectiveIn this study, we investigated various pubertal presentations and progressions before and after estrogen induction therapy and the correlations with Turner syndrome karyotypes.Materials and methodsWe reviewed the medical records of patients with Turner syndrome diagnosed before the age of 18 years between 2000 and 2019. Sixty-six patients were enrolled and distributed into 45,X monosomy group, X chromosome structural abnormalities group and X mosaicism group. The pubertal presentations were classified into spontaneous puberty, arrested puberty and no spontaneous puberty. All patients’ karyotypes, pubertal progressions and laboratory data were collected and analyzed.ResultsThe karyotypes were highly correlated with pubertal presentations. No spontaneous puberty was noticed in 58.3% 45,X monosomy patients, 50% patients with X chromosome structural abnormalities had arrested puberty, whereas 70% patients with X mosaicism had spontaneous puberty. Estrogen induction therapy in patients with no spontaneous puberty could induce puberty and the tempo of puberty may approximate to the spontaneous puberty group (median, 2.3 vs. 2.2 years, P = 0.95). In both interventional groups, the FSH level was distinguishable before treatment (median, 65.1 vs. 100.4 mIU/mL, P = 0.02). After long term estrogen therapy, the FSH could be suppressed to similar level in both interventional groups (median, 37.5 vs 34.5 mIU/mL, P = 0.84). Neither LH nor E2 level provided valuable information before and after treatment.ConclusionThe karyotypes were highly correlated with pubertal presentations at Turner syndrome patients. The integrity of 2nd X chromosome plays an important role. Low dose estrogen could mimic the tempo of puberty even delay induction age at Taiwan. The FSH data could provide predictive information of pubertal induction for both interventional groups.