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.     

Clinical picture in patients with 46,X,i(Xq) karyotype. Are there differences from Turner syndrome?

Clinical presentation in 2 patients with 46,X,i(Xq)-Karyotype are described. In both cases no mosaicism could be detected. The two patients show the classical features of gonadal dysgenesis: short stature, sexual infantilism and primary amenorrhea due to streak ovaries. Other characteristic somatic manifestations of the Turner syndrome such as webbing of the neck, however, were missing. In one of the two cases a Hashimoto's thyroiditis was present, which has been repeatedly reported before in the literature in cases with 46,X,i(Xq)-karyotype.     

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.     

Gonadal dysgenesis in own material]

Eleven patients with Turner syndrome and 6 with pure gonadal dysgenesis were examined. Diagnosis was made on the base of clinical and cytogenetic examination. All patients had primary amenorrhea and underdevelopment of primary, secondary and tertiary sexual features. Hormonal estimations revealed elevated FSH serum concentration in women with Turner syndrome and with pure gonadal dysgenesis (46, XY) vs. to patients with 46, XX. Estradiol and Progesterone levels were low in all cases. All women were treated with estrogens and progestational agents in sequential manner with good results. We did not observe significant phenotypic differences between patients with monosomie X and patients with structural abnormalities within chromosome X and mosaicism.     

Testicular feminization syndrome in the neonate

If we see a young, phenotypically female patient with an XY karyotype, it is of great importance to differentiate between the testicular feminization syndrome and gonadal dysgenesis. Patients with testicular feminization will always have normal testes, which are situated either in the ovarian fossa or in the inguinal canal. Patients with gonadal dysgenesis always have streak gonads. The risk of developing a malignancy in an abnormally located testis is very low, certainly before puberty, whereas the risk for dysgenetic gonads to develop a malignancy is high. Testes in patients with testicular feminization have an important endocrine function in puberty, whereas in gonadal dysgenesis patients they do not. For these reasons, in patients with testicular feminization, one should not remove the testes until the completion of puberty, whereas in patients with gonadal dysgenesis removal should be performed immediately upon recognition of the disorder.     

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.     

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.     

Gonadendysgenesie aus gyn?kologischer Sicht

Gonadal dysgenesis (GD) belongs to the group of disorders/differences of sex development (DSD) and is based on an inborn faulty or missing development of the gonads. In complete loss of function or if no testosterone and no testicular anti-mullerian hormone (AMH) is produced, streak gonads and a female phenotype (usually with uterus) arise even in cases of a male karyogram. Leading symptom is primary, hypergonadotropic amenorrhea with normal body height and usually without associated anomalies, with the exception of the Turner syndrome and other rare syndromes. A partial loss of function of the gonads leads to premature ovarian failure (POF) in 46,XX GD and to ambiguous external genitalia in 46,XY GD. In cases with Y in the karyogram, the gonads must be removed due to the risk of up to 30% of malignant development. Associated anomalies, adrenocortical insufficiency and short stature necessitate an interdisciplinary approach, hormone therapy for induction of breast development and prevention of osteoporosis should be initiated by gynecologists.     

The importance of determining karyotype in premenarchal females with gonadal dysgerminoma: two case reports

Abstract. Gonadal dysgerminomas developed in two girls, aged 12 and 15 years. Both were initially treated with conservative unilateral gonadectomy. Forty-six, XY gonadal dysgenesis was not suspected in either patient due to the normal appearance of the contralateral gonads and internal female genital organs. One died of a second germ cell malignancy which developed in the contralateral ovary 9½ years later. The diagnosis of 46, XY gonadal dysgenesis was established by karyotype in both patients. Although conservative surgical management is desirable for nulliparous women with unilateral dysgerminomas, the presence of 46, XY gonadal dysgenesis should be suspected in all premenarchal girls with ovarian germ cell malignancies. If karyotyping reveals the presence of an Y chromosome, bilateral gonadectomy is indicated because of the risk that another neoplasm may develop in the contralateral ovary.     

Familial 46,XY pure gonadal dysgenesis and gonadoblastoma/dysgerminoma: case report

The case reports of two sisters admitted for evaluation of primary amenorrhea are presented. Gynecological and endocrinological investigations and chromosomal analysis led to the diagnosis of familial 46,XY gonadal dysgenesis. Both sisters underwent bilateral salpingo-oophorectomy and hysterectomy. Histological examination revealed dysgenetic gonads with gonadoblastoma and dysgerminoma. Five years after treatment by surgery and irradiation the patients are well and free of recurrence. These cases again confirm the risk of malignancy and the necessity of prophylactic gonadectomy in all patients with gonadal dysgenesis and Y chromosomal material.     

Chromosomal complements in primary gonadal failure

Twenty-nine patients underwent clinical, hormonal, endoscopic, and cytogenetic studies to determine the cause of primary amenorrhea or delayed sexual development. In 19 of them (mean age 17.6 years), the X chromosome was either missing or anomalous. In ten patients (mean age 25.5 years), the chromosomal complement was normal, 46 XX in six patients and 46 XY in four patients. Those with abnormal chromosomal complements were shorter (mean height, 141.9 cm) than patients with normal complements (158.7 cm). Somatic stigmas were observed more frequently in patients with chromosomally abnormal primary gonadal failure. In 23 patients (79.3%), the gonads were streaks, with fibrous stroma devoid of either follicles or tubules containing germ cells. In three patients the ovaries were hypoplastic, with few primordial follicles. Gonadoblastoma was present in two patients with XY and mixed XX/X/XY gonadal dysgenesis. In every patient with streak gonads and lack of germ cells, serum gonadotropin levels were elevated. Karyotype, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) assays, and eventually laparoscopy and gonadal biopsy are important in the management of patients with primary gonadal failure.     

Sex chromosomal mosaicism in the gonads of patients with gonadal dysgenesis, but normal female or male karyotypes in lymphocytes

OBJECTIVES: In most cases, XX or XY gonadal dysgenesis remains genetically unexplained. In this pilot study we searched for sex-chromosomal mosaicism in gonads of patients with XX or XY gonadal dysgenesis of undetermined origin. STUDY DESIGN: Gonadal tissues were analyzed by cytogenetic and interphase fluorescence in-situ hybridization (FISH) analyses in four patients with gonadal dysgenesis and normal female (46,XX) or male (46,XY) karyotypes in lymphocytes. RESULTS: Cytogenetic and FISH analyses of the gonads demonstrated in three patients a sex-chromosomal mosaicism. Cytogenetic analysis of gonadal tissue of the fourth patient confirmed the result of the lymphocytes with 46,XX, but FISH analysis revealed in 17% of nuclei only one X-chromosome. CONCLUSION: Our data indicate that sex-chromosomal mosaicism in gonads may be a frequent cause of gonadal dysgenesis despite of normal karyotypes in lymphocytes. Therefore, cytogenetic and FISH analyses of gonadal tissue can provide important information in unexplained cases of gonadal dysgenesis.     

Síndrome de insensibilidad a los andrógenos como causa de amenorrea primaria

Androgen insensitivity syndrome is characterized by the presence of external female phenotype, 46,XY karyotype and intraabdominal testes. This syndrome is the third most frequent cause of primary amenorrhea, after gonadal dysgenesis and congenital absence of the vagina (Mayer-Rokitansky-Küster-Hauser syndrome). Androgen insensitivity syndrome is of interest due to its role in sexual identification and its possible association with malignant tumors of the male gonads, which require an accurate diagnosis and surgical treatment. We present two cases of androgen insensitivity syndrome. The results of the clinical and genetic examinations, as well as the treatment and follow-up of these two patients, are discussed.     

Management of phenotypic female patients with an XY karyotype

Nine phenotypic female patients with XY karyotype were evaluated through a clinical, cytogenetic, hormonal, endoscopic and histologic diagnostic protocol. Seven patients complained of primary amenorrhea and two patients of abnormal puberal development. The final diagnosis was XY gonadal dysgenesis (n = 5) and testicular feminization syndrome (n = 4). Two patients were less than 155 cm tall, and the remainder were over 155. Minor somatic anomalies were found in two patients with XY gonadal dysgenesis. Patient with testicular feminization syndrome had FSH and LH within the normal range, and patients with XY gonadal dysgenesis had elevated FSH and LH levels. Gonadoblastomas were found in two patients with XY gonadal dysgenesis (one patient with XO/XX/XY mosaicism). Laparoscopy and gonadal biopsy might be useful in some patients to avoid confusion between XY gonadal dysgenesis and testicular feminization syndrome. Early diagnosis of XY gonadal dysgenesis is always desirable, and bilateral gonadectomy is indicated as soon as the diagnosis is made in patients with a Y chromosome and elevated FSH levels. Surgical removal of the gonads from patients with testicular feminization should be delayed until the completion of puberty because of the low risk of malignancy.     

Gonadoblastoma bilateral y disgerminoma asociados en un síndrome de Swyer

Swyer syndrome is a pure gonadal dysgenesis with female phenotype and 46 XY karyotype. Affected individuals have dysgenetic and non-functioning gonads. The risk of gonadal neoplasia is high at between 25% and 30%. The most frequently reported malignancies are gonadoblastoma and disgerminoma. We report a case of bilateral gonadoblastoma and dysgerminoma in a female patient with this syndrome.     

Gonadal dysgenesis and somatic stigmata in patients with 45,X/46,Xr(X) ring chromosome

Two cases of gonadal dysgenesis and stigmata of Turner's syndrome with ring chromosome X are described. Their features support the idea that ring chromosome X should be considered as a deletion in the genetic sense, affecting both the gonadal and statural determinants. Without knowing the cytogenetic findings, these patients are usually labeled as having Turner's syndrome. Furthermore, endocrine data and histologic examination of the gonads are indistinguishable from those of individuals with 45,X or 46XX gonadal dysgenesis.     

79例XY性腺发育异常患者性腺肿瘤发生情况分析

目的 探讨表型为女性、染色体含有Y或Y成分的性腺发育异常患者的性腺肿瘤发生情况.方法 1989年10月至2005年12月间于北京协和医院妇产科因性腺发育异常手术切除双侧性腺的患者共79例,所有患者均取外周血进行淋巴细胞染色体核型分析、Y基因性决定区检测以及相关激素和酶检测,影像学检查了解性腺位置.行经腹或腹腔镜下性腺切除术,所有手术标本均行病理检查.结果 79例患者中,雄激素不敏感综合征患者41例,其中发生精原细胞瘤1例、支持细胞腺瘤2例,占7%;170r羟化酶缺乏症患者14例,其中发生支持细胞腺瘤1例,占7%;XY单纯性腺发育不全患者4例,其中发生性腺母细胞瘤及无性细胞瘤1例,占1/4;XO/XY性腺发育不全患者16例,其中发生精原细胞瘤及性腺母细胞瘤1例,占6%;睾丸退化患者4例中无肿瘤发生.发生肿瘤的性腺多位于盆腔内,发生肿瘤的年龄集中于15～23岁.结论 表型为女性、染色体含有Y或Y成分的性腺发育异常患者易发生性腺母细胞瘤和生殖细胞肿瘤,一旦确诊宜及早切除双侧性腺.     

Hormonal and cytogenetic studies in phenotypically female patients with gonadal dysgenesis

In 4 cases of gonadal dysgenesis the clinical, hormonal, cytogenetic, and histological findings were correlated. There were 2 patients with 46,XY karyotype, one patient with 45,X Turner's syndrome and one patient with a 46,XX chromosome complement. All patients had streak gonads with ovarian stroma. In one phenotypically female 46,XY individual an involuted gonadoblastoma was found. Her testosterone was four-fold higher in gonadal vein blood compared to peripheral blood. Cytogenetic analysis of multiple tissues in both cases with the 46,XY karyotype greatly reduced the probability of mosaicism. In the patient with 45,X Turner's syndrome and in the one with 46,XX gonadal dysgenesis only peripheral blood cells were karyotyped and mosaicism was not further excluded by analysis of other tissues. The concentrations of steroid hormones in gonadal vein blood were low. The levels ranged as follows: estrone 41-98 pg/ml, estradiol 18-90 pg/ml, testosterone 37-294 ng/100 ml, dihydrotestosterone 13-22 ng/100 ml, and progesterone 0.3-1.5 ng/ml. It was concluded that gonadal streaks were similarly deficient in biosynthesis of steroid hormones despite different chromosomal complements.     

Disgerminoma y síndrome de Swyer

Swyer syndrome is a pure gonadal dysgenesis with a 46XY karyotype, normal female phenotype, and complete lack of functioning gonadal tissue, which is represented by bilateral, nonfunctioning, rudimentary streak gonads composed of fibrous tissue, with normal female internal genitalia. They present most often with primary amenorrhea. To date, 20% of these are explained by a mutation or a deletion in SRY. In 80%, SRY is apparently normal. The risk of gonadal neoplasia is high, dictating early prophylactic removal of these dysgenetic gonads. Laparoscopic surgery is recommended. Gonadoblastoma and dysgerminoma are the most frequently reported malignancies.     

Coexistence of Mayer-Rokitansky-Küster-Hauser Syndrome and Turner Syndrome: A Case Report

BackgroundTurner syndrome is a common chromosomal disorder, with an incidence of 1 in 2000 live-born female infants. Mayer-Rokitansky-Küster-Hauser syndrome (MRKH) affects 1 in 4500 female births and, rarely, it might be associated with gonadal dysgenesis.CaseA 17-year-old girl was referred to our clinic with short stature and primary amenorrhea. The patient was diagnosed with Turner syndrome and underwent estrogen therapy. At the age of 24 years, just after the patient's sexual initiation, the first complete gynecological examination was performed. A blind-ending vagina was revealed and the patient was diagnosed with MRKH.Summary and ConclusionEarly diagnosis of coexistence of MRKH and Turner syndrome, although very difficult, might prevent patients from developing serious complications.