scholarly journals Unraveling of Diagnosis Odyssey in A Girl with Primary Amenorrhea: A case report

2020 ◽  
Vol 6 (1) ◽  
pp. 19-22
Author(s):  
Ni Made Indri Dwi Susanti ◽  
Inu Mulyantoro ◽  
Dik Puspasari ◽  
Nurin Aisyiyah Listyasari ◽  
Sultana MH Faradz
Keyword(s):  
Gonadal Dysgenesis ◽  
Histopathological Examination ◽  
Laboratory Data ◽  
External Genitalia ◽  
Primary Amenorrhea ◽  
Normal Range ◽  
Immunohistochemical Markers ◽  
Sex Development ◽  
Pathogenic Variants ◽  
The Right

ABSTRACT Background:Primary amenorrhea may result from congenital abnormalities in the development of the gonads, genital tract, or external genitalia or from a disturbance within the hypothalamic-pituitary-ovarian axis. Gonadal dysgenesis is a disorder of sex development in which the diagnosis is based on the histology of gonads and is the main cause of primary amenorrhea. Optimal protocol of management for phenotypic female with 46, XY gonadal dysgenesis involves prophylactic gonadectomy at diagnosis.Case Presentation: The patient was referred to our hospital at the age of 15 years old for primary amenorrhea. She was obese with no secondary sex sign. Gynecologic examination revealed a normal vagina and clitoris. Rectal Toucher examination revealed no internal genitalia structure. The laboratory data: FSH levels was above normal range, LH and testosterone levels were within normal range. Pelvic Ultrasonography uterus and vaginal structure and testis were not visualized. Cytogenetic and ARgene analysis found a 46, XY karyotype and no pathogenic variants. On laparoscopy, Mullerian structure and Wolffian remnant structure were identified and biopsies were performed. Based on histopathological examination and immunohistochemical markers of the right and left gonad showed the impression of Malignant Mixed Germ Cell-Sex Cord Stromal Tumor. SRY gene examination was positive.Examination of other DSD gene analysis has not been done. Second laparoscopy for gonadectomy and removal of Mullerian and Wolfiian remnant structure were performed. Conclusion:Chromosomal analysis should become the first line testing in primary amenorrhea followed by advanced molecular test. Multidisciplinary managements recommended for DSD cases.

WT1 Pathogenic Variants are Associated with a Broad Spectrum of Differences in Sex Development Phenotypes and Heterogeneous Progression of Renal Disease

2021 ◽  
pp. 1-9
Author(s):  
Maria T.M. Ferrari ◽  
Andreia Watanabe ◽  
Thatiane E. da Silva ◽  
Nathalia L. Gomes ◽  
Rafael L. Batista ◽  
...  
Keyword(s):  
Kidney Development ◽  
Wilms Tumor ◽  
Genetic Diagnosis ◽  
Germ Cell Tumors ◽  
Disorders Of Sex Development ◽  
Medical Attention ◽  
Primary Amenorrhea ◽  
Normal Female ◽  
Sex Development ◽  
Pathogenic Variants

Wilms’ tumor suppressor gene 1 (<i>WT1</i>) plays an essential role in urogenital and kidney development. Heterozygous germline pathogenic allelic variants of <i>WT1</i> have been classically associated with Denys–Drash syndrome (DDS) and Frasier syndrome (FS). Usually, exonic pathogenic missense variants in the zinc finger region are the cause of DDS, whereas pathogenic variants affecting the canonic donor lysine-threonine-serine splice site in intron 9 cause FS. Phenotypic overlap between <i>WT1</i> disorders has been frequently observed. New <i>WT1</i> variant-associated phenotypes, such as 46,XX testicular/ovarian-testicular disorders of sex development (DSD) and primary ovarian insufficiency, have been reported. In this report, we describe the phenotypes and genotypes of 7 Brazilian patients with pathogenic <i>WT1</i> variants. The molecular study involved Sanger sequencing and massively parallel targeted sequencing using a DSD-associated gene panel. Six patients (5 with a 46,XY karyotype and 1 with a 46,XX karyotype) were initially evaluated for atypical genitalia, and a 46,XY patient with normal female genitalia sought medical attention for primary amenorrhea. Germ cell tumors were identified in 2 patients, both with variants affecting alternative splicing of <i>WT1</i> between exons 9 and 10. Two pathogenic missense <i>WT1</i> variants were identified in two 46,XY individuals with Wilms’ tumors; both patients were &#x3c;1 year of age at the time of diagnosis. A novel <i>WT1</i> variant<i>,</i> c.1453_1456 (p.Arg485Glyfs*14), was identified in a 46,XX patient with testicular DSD. Nephrotic proteinuria was diagnosed in all patients, including 3 who underwent renal transplantation after progressing to end-stage kidney disease. The expanding phenotypic spectrum associated with <i>WT1</i> variants in XY and XX individuals confirms their pivotal role in gonadal and renal development as well as in tumorigenesis, emphasizing the clinical implications of these variants in genetic diagnosis.

45,X/46,XY ovotesticular disorder of sex development revisited: undifferentiated gonadal tissue may be mistaken as ovarian tissue

2017 ◽  
Vol 30 (8) ◽  
Author(s):  
Juliana Gabriel Ribeiro de Andrade ◽  
Liliana Aparecida Lucci De Angelo Andrade ◽  
Gil Guerra-Junior ◽  
Andréa Trevas Maciel-Guerra
Keyword(s):  
Germ Cells ◽  
Gonadal Dysgenesis ◽  
Case Reports ◽  
Ovarian Tissue ◽  
Case Presentation ◽  
Disorder Of Sex Development ◽  
Gonadal Tissue ◽  
Sex Development ◽  
Genital Ambiguity ◽  
The Right

AbstractBackground:The 45,X/46,XY karyotype has been associated with mixed gonadal dysgenesis (MGD) and ovotesticular disorder of sex development (DSD). Our aim was to revise the diagnosis of ovotesticular DSD in two patients in the context of a retrospective study of 45,X/46,XY subjects with genital ambiguity.Case presentation:Patient 1 had a left streak gonad; the right one was considered an ovotestis. Patient 2 had a right testis; the left gonad was considered an ovary. Revision of the histological sections was performed. Both the “ovarian” part of the right gonad of patient 1 and the left “ovary” of patient 2 contained ovarian-type stroma with clusters of sex-cordlike structures and rare germ cells, compatible with undifferentiated gonadal tissue (UGT). Misdiagnosis of ovarian tissue in patients with 45,X/46,XY mosaicism or its variants could also be found in six published case reports.Conclusions:A distinction between 45,X/46,XY ovotesticular DSD and MGD should be made on past and future cases keeping in mind that UGT may be mistaken as ovarian tissue.

Pure gonadal dysgenesis (Swyer syndrome) due to microdeletion in the SRY gene: a case report

2015 ◽  
Vol 28 (1-2) ◽  
Author(s):  
Gül Yesiltepe Mutlu ◽  
Heves Kırmızıbekmez ◽  
Hatip Aydın ◽  
Handan Çetiner ◽  
Serdar Moralıoğlu ◽  
...  
Keyword(s):  
Gonadal Dysgenesis ◽  
External Genitalia ◽  
Delayed Puberty ◽  
Sex Characteristics ◽  
Primary Amenorrhea ◽  
Laboratory Findings ◽  
Secondary Sex Characteristics ◽  
Disorder Of Sexual Development ◽  
Swyer Syndrome

Abstract46,XY complete gonadal dysgenesis (Swyer syndrome) is a rare cause of disorder of sexual development. This syndrome is caused by a defect in the determination of sex during embryogenesis and is characterised with female external genitalia, normal or rudimentary uterus, and streak gonads, despite the presence of the 46,XY karyotype. Most of the studied cases presented with leak of secondary sex characteristics and primary amenorrhea during adolescence. Laboratory findings reveal hypergonadotropic hypogonadism. Herein we present the case of a female with a 46,XY karyotype who was admitted with delayed puberty and detected to have a microdeletion in the

scholarly journals Rare case of complete gonadal dysgenesis 46 XY, Swyer syndrome

2017 ◽  
Vol 5 (2) ◽  
pp. 714
Author(s):  
Aravind Chander ◽  
Reshma Shri ◽  
Arun Muthuvel ◽  
Chandralekha Veluswamy
Keyword(s):  
Gonadal Dysgenesis ◽  
External Genitalia ◽  
Sexual Life ◽  
Primary Amenorrhea ◽  
Female Type ◽  
The Past ◽  
Donor Oocyte ◽  
Swyer Syndrome ◽  
Made In ◽  
Complete Gonadal Dysgenesis

Swyer syndrome also known as 46XY complete gonadal dysgenesis is a rare cause of primary amenorrhea. These patients are phenotypically females with female type of internal and external genitalia with absence of testicular tissues. They have streak gonads which have increased potential to turn into malignancy.  Bilateral gonadectomy should be done as soon as diagnosis is made. In present case, 20 years unmarried female came with complaints of menstrual bleeding only on taking medication. She never attained menarche, following which she was started on treatment outside, on withdrawal bleeding for the past 3 years. She was now evaluated and diagnosed as Swyer syndrome and bilateral gonadectomy was done laproscopically. Swyer syndrome patients can get married, have normal sexual life and can get pregnant through invitro fertilisation with donor oocyte if desired.

scholarly journals Misdiagnosis of Mullerian agenesis in a patient with 46, XX gonadal dysgenesis: a missed opportunity for prevention of osteoporosis

2019 ◽  
Vol 2019 ◽  
Author(s):  
Yotsapon Thewjitcharoen ◽  
Veekij Veerasomboonsin ◽  
Soontaree Nakasatien ◽  
Sirinate Krittiyawong ◽  
Thep Himathongkam
Keyword(s):  
Gonadal Dysgenesis ◽  
Hormone Replacement ◽  
Disorders Of Sex Development ◽  
Primary Amenorrhea ◽  
List Type ◽  
Hormone Substitution ◽  
Mrkh Syndrome ◽  
Sex Development ◽  
Exogenous Estrogen ◽  
Müllerian Agenesis

Summary Primary amenorrhea could be caused by disorders of four parts: disorders of the outflow tract, disorders of the ovary, disorders of the anterior pituitary, and disorders of hypothalamus. Delay in diagnosis and hormone substitution therapy causes secondary osteoporosis. Herein, we report a case of a 23-year-old phenotypical female who presented with primary amenorrhea from 46, XX gonadal dysgenesis but had been misdiagnosed as Mayer–Rokitansky–Kuster–Hauser (MRKH) syndrome or Mullerian agenesis. The coexistence of gonadal dysgenesis and MRKH was suspected after laboratory and imaging investigations. However, the vanishing uterus reappeared after 18 months of hormone replacement therapy. Therefore, hormone profiles and karyotype should be thoroughly investigated to distinguish MRKH syndrome from other disorders of sex development (DSD). Double diagnosis of DSD is extremely rare and periodic evaluation should be reassessed. This case highlights the presence of estrogen deficiency state, the uterus may remain invisible until adequate exposure to exogenous estrogen. Learning points: An early diagnosis of disorders of sex development (DSD) is extremely important in order to promptly begin treatment, provide emotional support to the patient and reduce the risks of associated complications. Hormone profiles and karyotype should be investigated in all cases of the presumptive diagnosis of Mayer–Rokitansky–Kuster–Hauser (MRKH) syndrome or Mullerian agenesis. The association between 46, XX gonadal dysgenesis and Mullerian agenesis has been occasionally reported as a co-incidental event; however, reassessment of the presence of uterus should be done again after administration of exogenous estrogen replacement for at least 6–12 months. A multidisciplinary approach is necessary for patients presenting with DSD to ensure appropriate treatments and follow-up across the lifespan of individuals with DSD.

scholarly journals Chance diagnosis of mixed gonadal dysgenesis in an adult case of malignant gonadal germ cell tumor: a case report

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Yoshiko Kurose ◽  
Tomonori Nagai ◽  
Kousuke Shigematsu ◽  
Takahiro Uotani ◽  
Taichi Akahori ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Germ Cell ◽  
Germ Cell Tumor ◽  
Gonadal Dysgenesis ◽  
Disorders Of Sex Development ◽  
External Genitalia ◽  
Tumor Formation ◽  
Cell Tumor ◽  
Primary Amenorrhea ◽  
Mixed Gonadal Dysgenesis

Abstract Background Mixed gonadal dysgenesis (MGD) is a subtype of the disorders of sex development (DSD) associated with sex chromosome abnormalities characterized by abnormal external genitalia, short stature, and primary amenorrhea. This disease is generally diagnosed from the neonatal stage to early childhood, and by puberty at the latest. Cases that are phenotypically female or those with ambiguous genitalia experience a high risk of gonadal tumor formation. As tumor risk is known to increase with age, prophylactic bilateral gonadectomy is recommended following early diagnosis. Case presentation Here we report a case of an adult Japanese woman diagnosed with MGD during treatment for a giant pelvic tumor. The patient initially visited a gynecology clinic during puberty for primary amenorrhea, at which time an abnormality was found with the external genitalia. However, a diagnosis of MGD was not made at this time, resulting in the development of a malignant gonadal germ cell tumor in adulthood. Conclusions For early diagnosis of MGD and the prevention of gonadal tumor formation, it is essential that gynecologists fully understand MGD and other DSD.

scholarly journals Rupture and hemorrhage of a seminoma mixed with yolk sac tumors in 46XY partial gonadal dysgenesis: a case report and literature review

BMC Surgery ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Rui Lin ◽  
Nanbin Liu ◽  
Xiuyan Wang ◽  
Xuyou Zhu ◽  
Daojing Huang ◽  
...  
Keyword(s):  
Abdominal Pain ◽  
Case Report ◽  
Literature Review ◽  
Germ Cell ◽  
Gonadal Dysgenesis ◽  
Yolk Sac ◽  
Sex Development ◽  
Yolk Sac Tumors ◽  
Partial Gonadal Dysgenesis ◽  
The Right

Abstract Background 46XY partial gonadal dysgenesis (PGD) is a rare subtype of disorder of sex development (DSD). 46YY PGD is a congenital disease with atypical chromosomal, gonadal, or anatomical sex development. The patient in this case report had male and female genitalia simultaneously. We created a flowchart of the differential diagnosis for clinicians. Case presentation A 41-year-old male was admitted to the hospital complaining of lower quadrant abdominal pain for 1 day. Physical examination revealed that his penis size was normal, but a urethral orifice was located in the perineum area between the scrotum and anus. One small testicle was in the left scrotum, but no testicle was present on the right. The patient’s abdomen was bulging, and he had lower abdominal pain. According to the emergency CT scan, a lesion (74*65 mm) was found in the right pelvis between the bladder and rectum. The lesion showed an unclear boundary and hematocele appearance. The lesion was removed by emergency surgery, and the pathology report indicated a mixed germ cell tumor with a seminoma and yolk sac tumors. Conclusion This article is a case report of germ cell tumors in 46XY PGD patients. The literature review summarizes the clinical diagnosis, and a flowchart is provided for physicians in future practice. The importance of this report is that it will help acquaint physicians with this rare disease and make the right initial clinical decision quickly through the use of this flowchart. However, the variants of special subtypes of 46XY DSD are myriad, and all the diagnoses could not be covered in one flowchart.

scholarly journals Dysgerminoma presenting at fifty, consequence to undiagnosed Swyer syndrome

2021 ◽  
Vol 10 (8) ◽  
pp. 3249
Author(s):  
Sapna Vinit Amin ◽  
Aswathy Kumaran
Keyword(s):  
High Risk ◽  
Female Patient ◽  
Gonadal Dysgenesis ◽  
Primary Amenorrhea ◽  
Ovarian Malignancy ◽  
Disorder Of Sex Development ◽  
Sex Development ◽  
Male Karyotype ◽  
Swyer Syndrome ◽  
Complete Gonadal Dysgenesis

Swyer syndrome or XY complete gonadal dysgenesis (CGD) is a rare disorder of sex development (DSD) characterized by presence of dysgenetic gonads in a phenotypically female patient with a male karyotype. Usually Swyer syndrome is diagnosed following appropriate evaluation for amenorrhea in adolescence and prophylactic gonadectomy is done as these patients have high risk of developing malignancy in their dysgenetic gonads.  Here we presented patient who presented later in life with ovarian malignancy which turned out to be a consequence of undiagnosed Swyer syndrome. Her case exemplifies that fact that improper evaluation of primary amenorrhea in adolescence and omission to do prophylactic bilateral gonadectomy led to her presenting with malignancy at this advanced age. Therefore, be aware to not let Swyer syndrome go undiagnosed and mismanaged.

A Small Supernumerary Xp Marker Chromosome Including Genes NR0B1 and MAGEB Causing Partial Gonadal Dysgenesis and Gonadoblastoma

2021 ◽  
pp. 1-9
Author(s):  
Mirian Yumie Nishi ◽  
José Antônia Diniz Faria Júnior ◽  
Ana Cristina Victorino Krepischi ◽  
Daniela Rodrigues de Moraes ◽  
Silvia Souza da Costa ◽  
...  
Keyword(s):  
Gonadal Dysgenesis ◽  
Marker Chromosome ◽  
Copy Number Variations ◽  
Breast Development ◽  
Chromosomal Microarray ◽  
Primary Amenorrhea ◽  
Chromosomal Microarray Analysis ◽  
Fish Analysis ◽  
Sex Development ◽  
Partial Gonadal Dysgenesis

Copy number variations of several genes involved in the process of gonadal determination have been identified as a cause of 46,XY differences of sex development. We report a non-syndromic 14-year-old female patient who was referred with primary amenorrhea, absence of breast development, and atypical genitalia. Her karyotype was 47,XY,+mar/46,XY, and FISH analysis revealed the X chromosome origin of the marker chromosome. Array-CGH data identified a pathogenic 2.0-Mb gain of an Xp21.2 segment containing <i>NR0B1/DAX1</i> and a 1.9-Mb variant of unknown significance from the Xp11.21p11.1 region. This is the first report of a chromosomal microarray analysis to reveal the genetic content of a small supernumerary marker chromosome detected in a 47,XY,+der(X)/46,XY karyotype in a non-syndromic girl with partial gonadal dysgenesis and gonadoblastoma. Our findings indicate that the mosaic presence of the small supernumerary Xp marker, encompassing the <i>NR0B1/DAX1</i> gene, may have been the main cause of dysgenetic testes development, although the role of <i>MAGEB</i> and other genes mapped to the Xp21 segment could not be completely ruled out.

scholarly journals The evolving role of whole-exome sequencing in the management of disorders of sex development

2021 ◽  
Author(s):  
Yardena Tenenbaum Rakover ◽  
Osnat Admoni ◽  
Gadir Elias-Assad ◽  
Shira London ◽  
Marie Noufi Barhoum ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
De Novo ◽  
Disorders Of Sex Development ◽  
External Genitalia ◽  
Sex Development ◽  
Pathogenic Variants ◽  
Extensive Evaluation ◽  
Whole Exome

Objective: Disorders of sex development (DSD) are defined as congenital conditions in which development of chromosomal, gonadal and anatomical sex is atypical. Despite wide laboratory and imaging investigations, the etiology of DSD is unknown in over 50% of patients. Methods: We evaluated the etiology of DSD by whole-exome sequencing (WES) at a mean age of 10 years in nine patients for whom extensive evaluation, including hormonal, imaging and candidate gene approaches, had not identified an etiology. Results: The eight 46,XY patients presented with micropenis, cryptorchidism and hypospadias at birth and the 46,XX patient presented with labia majora fusion. In seven patients (78%), pathogenic variants were identified for RXFP2, HSD17B3, WT1, BMP4, POR, CHD7 and SIN3A. In two patients, no causative variants were found. Mutations in three genes were reported previously with different phenotypes: an 11-year-old boy with a novel de novo variant in BMP4; such variants are mainly associated with microphthalmia and in few cases with external genitalia anomalies in males, supporting the role of BMP4 in the development of male external genitalia; a 12-year-old boy with a known pathogenic variant in RXFP2, encoding insulin-like 3 hormone receptor, and previously reported in adult men with cryptorchidism; an 8-year-old boy with syndromic DSD had a de novo deletion in SIN3A. Conclusions: Our findings of molecular etiologies for DSD in 78% of our patients indicate a major role for WES in early DSD diagnosis and management, and highlights the importance of rapid molecular diagnosis in early infancy for sex of rearing decisions.

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