Novel mutation of MAP3K1 gene in 46,XY DSD with complete gonadal dysgenesis

ObjectiveSwyer syndrome, or 46, XY complete gonadal dysgenesis, is a disorder of human sexual development which present with female external genitalia, lack of female reproductive organs, and a 46, XY karyotype. Many genes that participate in human sexual development have been implicated in the pathogenesis of 46, XY gonadal dysgenesis.Case reportA 18-year-old phenotypically female was presented with primary amenorrhea. Surveillance revealed hypergonadotropic hypogonadism, a normal male 46, XY karyotype and absent of functional gonad, which was confirmed by pathological examination of the streak gonad. Whole exome sequencing showed germline mutations of a novel missense variant, c.570G > C, p.Lys190Asn, in exon 2 of MAP3K1 gene.ConclusionGiven evolutionary conservation of lysine residue at position 190, the amino acid substitution may interfere with interaction between MAP3K1 and RHOA, and contributes to complete gonadal dysgenesis in the context of 46,XY.     

Clinical features and management of 33 patients with 46,XX pure gonadal dysgenesis

The objective of the study is to summarize the clinical characteristics of 33 patients’ cohort (46,XX pure gonadal dysgenesis, 46,XX PGD), discuss the management, and propose treatment suggestions. Patients’ information, medical history, and medical records were obtained. All patients were closely followed up. At the time of diagnosis, the patients presented 19.53?±?3.60 years old, 165?±?6.49?cm height, breast development of Tanner stage I, and infantile female genitalia. High level of follicle-stimulating hormone (87.41?±?21.50 mIU/mL) and LH (27.10?±?8.47 mIU/mL) and low level of E2 (8.85?±?6.13?pg/mL) were observed. Individualized hormone replacement therapy (HRT) was initiated after diagnosis. After 2 years of treatment, all patients had obvious breast development; the uterus showed (2.38?±?0.60)?×?(1.38?±?0.70)?×?(1.38?±?0.55) cm growth. The incidence of osteopenia changed from 69.70% to 22.22% and that of osteoporosis changed from 18.18% to 0. Dysgeminoma was found in one patient. We concluded that gonadal dysgenesis in 46,XX PGD causes secondary sexual characteristic absence, tendency of taller, osteoporosis, infertility, and sexual health problems. There is minor chance of tumor occurrence for the patients. Optimal care including HRT and close follow-up are required.     

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.     

Gonadoblastoma-Associated Mixed Gonadal Germ Cell Tumor with Dysgerminoma and Hepatoid Yolk Sac Tumor Components in 46XY Gonadal Dysgenesis

BackgroundDisorders of sex development are congenital conditions with atypical chromosomal, gonadal, or anatomical sex development. Gonadal dysgenesis in patients containing a Y chromosome have a high risk of developing germ cell tumors with potential for malignant transformation.CaseWe present the case of a 17-year-old phenotypic female with primary amenorrhea and 46,XY complete gonadal dysgenesis. Pelvic ultrasound showed a solid cystic lesion in the right gonad. Pathology showed a gonadoblastoma-associated mixed gonadal germ cell tumor with dysgerminoma and hepatoid yolk sac tumor.Summary and ConclusionTo our knowledge, this mixed neoplasm association has not been previously reported and this case illustrates the challenges for the diagnosis of gonadal dysgenesis-associated tumors, emphasizing its recognition and prognostic implications.     

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.     

46,XY单纯性腺发育不全10例分析

目的 探讨染色体核型为46，XY单纯性腺发育不全患者的诊断及治疗。方法 分析1984-01—2004-07北京协和医院妇产科收治的10例染色体核型为46，XY的单纯性腺发育不全病例。所有病例均行剖腹探查术或腹腔镜探查术。结果 患者的生长和智力发育正常，但部分患者上肢长，指距大于身高。表现为原发闭经，青春期无女性第二性征发育，无阴、腋毛或稀少，乳房不发育。内外生殖器发育幼稚，术中均可见到发育不良的子宫，正常或发育欠佳的输卵管，以及条索状性腺组织。手术切除条索状性腺组织，病理为原始的睾丸组织。所有患者均有阴道，人工周期可来月经。结论 正确及时诊断46，XY单纯性腺发育不全十分重要，确诊后需行手术切除腹腔内发育不良的睾丸组织，术后予激素治疗以维持女性的社会性别。     

性腺发育异常患者的生育问题

性腺发育异常是指患者性腺性别异常的一类先天性疾病。现代诊疗多采用激素补充和手术治疗,可有效促进性腺发育异常患者内外生殖器的发育,维持激素平衡,并预防肿瘤发生。在对性腺发育异常患者进行管理的过程中,需对患者的生殖潜力予以考虑。尽管大部分性腺发育异常患者合并不孕,但辅助生殖技术为性腺发育异常患者提供了供卵、体外受精-胚胎移植等多种治疗选择。性腺发育异常患者可通过个体化的治疗成功妊娠并分娩正常胎儿,获得良好的母婴结局,实现生育愿望。文章着重就性腺发育异常患者的生殖潜力及生育问题的治疗进行阐述。     

A psychosexual follow-up study of patients with mixed or partial gonadal dysgenesis

STUDY OBJECTIVE: To provide late adolescent and young adult psychosexual follow-up information on a consecutive series of patients with either mixed or partial gonadal dysgenesis. SETTING: Children's Memorial Health Institute (Warsaw, Poland). PARTICIPANTS: 19 patients (age range, 17-26 years), 9 raised as females and 10 raised as males. MEASURES: Clinical interview and psychologic tests were used to evaluate gender identity, gender role, and sexual behavior. RESULTS: All patients raised as male had a normal male gender identity, displayed masculine gender role behavior in childhood, and had a heterosexual sexual orientation. Seven of the 10 male patients had experienced heterosexual intercourse. Two out of nine women did not identify with the female gender. The majority had masculine gender role interests in childhood. The female patients were significantly less likely to have experienced sexual activity with a partner than the male patients. CONCLUSION: Although gender identity differentiated largely in accordance with sex assignment or sex of rearing in our sample, the patients reared as female appeared to have poorer sexual adjustment than the males. Cultural factors may have impacted on this latter outcome.     

单纯性腺发育不全与性腺母细胞瘤

46,XY单纯性腺发育不全是一种罕见的假两性畸形。作者复习了有关文献,结合报道之二例就其发生及其与性腺肿瘤发生的关系进行了讨论。特别强调性腺发育不良者应尽早检查染色体核型,测定H—Y抗原值,以便指导治疗。