Disorder of Sex Development, Mosaic Genetic Disorder 45x, 46xy: A Case Report

Background. Disorder of sex development (DSD) is a congenital disorder associated with interference in chromosomes, gonads, or sexes anatomically. Individual affected with DSD can be recognized since birth due to external genital ambiguity. Sexual chromosome DSD occurred because sexual chromosome numeric or structural disorder. Mosaic karyotype 45X/46XY is among the rare sexual chromosome DSD with incidence less than 1:15,000 live births. DSD individuals are susceptible to stigmatization. This can cause stress, negative emotion, and social isolation. Therefore, DSD individual management should be done as optimal as possible. Case Presentation: Twelve years old girl complaining a bump arose from anterior side of her genital resembles male genital since 4 years prior to admission without micturition and defecation complains. Patient has not experienced menarche. On external genital examination, we found the normal female external genital such as mons pubis, pubic hair, labia majora, labia minora, hymen, perineum, but without clitoris which in this case it is replaced by a glans of penis, arising from anterior commissure of labia majora area, with an urethral estuary. Before the management is done, patient underwent multidiscipline consultations and further examinations. Subsequently, it was approved that the joint conference formation consisting obstetric and gynecology, urologist, and pediatric endocrinologist to determine the optimal management for the patient. Conclusion: In this case, diagnosis was made with history taking, clinical examination, and supporting investigation such as ultrasound imaging and could be followed by biochemistry test, voiding cystourethrography or genitogram to determine next management. Counseling should be done in detail towards the family to know what action is best for the patient. Multidiscipline team was required to get the optimum result either in medical, ethical, or religious point of view. Surgery in this case was considered followed by long term therapy afterwards.

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

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2017-0039 ◽

2017 ◽

Vol 30 (8) ◽

Cited By ~ 5

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.

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Child with ‘46, XX’ disorder of sex development: clues to diagnose aromatase deficiency

BMJ Case Reports ◽

10.1136/bcr-2019-232575 ◽

2019 ◽

Vol 12 (12) ◽

pp. e232575

Author(s):

Saurav Shishir Agrawal ◽

Partha Pratim Chakraborty ◽

Anirban Sinha ◽

Animesh Maiti

Keyword(s):

Bone Age ◽

Ambiguous Genitalia ◽

Tall Stature ◽

Polycystic Ovaries ◽

Disorder Of Sex Development ◽

Primary Amenorrhoea ◽

Sex Development ◽

Genital Ambiguity ◽

Life Threatening ◽

History Of

A diagnosis of congenital adrenal hyperplasia (CAH) in a ‘46, XX’ newborn with ambiguous genitalia is like a ‘knee jerk reaction’ of the paediatrician because of its higher frequency and life-threatening consequences if remain undiagnosed and hence untreated. Aromatase deficiency (AD), a rare cause of ‘46, XX’ disorder of sex development, mimics virilising CAH in many aspects; thus, the disease is often overlooked. Diagnosis of AD in women is much easier around puberty due to the presence of primary amenorrhoea, undeveloped breasts, androgen excess and tall stature with eunuchoid proportions. Diagnosing AD with confidence immediately after birth or during early childhood is a challenging task without genetic analysis. In resource-restricted settings, AD remains a diagnosis of exclusion particularly in this age group and history of maternal virilisation, non-progressive genital ambiguity, elevated gonadotrophins (follicle-stimulating hormone >>luteinising hormone), mildly delayed bone age with/without enlarged polycystic ovaries serve as important clues to the underlying AD.

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Down syndrome with Disorder of Sex development (DSD): A Rare Presentation

Bangladesh Journal of Child Health ◽

10.3329/bjch.v44i1.49698 ◽

2020 ◽

Vol 44 (1) ◽

pp. 48-51

Author(s):

Farzana Sharmin ◽

Suraiya Begum ◽

Ismat Jahan ◽

Roksana Parvin ◽

Dhiraj Chandra Biswas

Keyword(s):

Down Syndrome ◽

Child Health ◽

Congenital Malformations ◽

Social Cost ◽

Genetic Disorder ◽

Rare Presentation ◽

Disorder Of Sex Development ◽

Rare Association ◽

Sex Development ◽

Common Genetic Disorder

Down syndrome is the most common genetic disorder among live born infants, which is associated with a number of congenital malformations and requires a huge medical and social cost. Here, we report a very rare association in an infant with Down syndrome and XY disorder of sex development (DSD). Bangladesh J Child Health 2020; VOL 44 (1) :48-51

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MON-056 Rare X Chromosome Pericentric Inversion Associated with Ovotesticular Disorder of Sex Development

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.930 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Gil Guerra-Junior ◽

Ana Paula Santos ◽

Flavia M Oliveira ◽

Tarsis A P Vieira ◽

Nilma L V Campos ◽

...

Keyword(s):

X Chromosome ◽

Pericentric Inversion ◽

Chromosome 9 ◽

Urogenital Sinus ◽

Seminiferous Tubules ◽

Chromosome Inversion ◽

Disorder Of Sex Development ◽

Sex Development ◽

Genital Ambiguity ◽

The Right

Abstract Ovotesticular disorder of sex development (OT-DSD) is a rare condition characterized by coexistence of ovarian and testicular parenchyma, in separate gonads or in the same gonad (ovotestis), in individuals with variable degrees of genital ambiguity. Karyotype may be 46,XX (60%), 46,XY (10%), or there may be sex chromosomes abnormalities, including mosaicism, chimerism and structural anomalies (30%). A genetic origin may be identified in some subjects with normal XX or XY karyotype, but most cases are of unknown origin. Apparently balanced chromosome rearrangements (translocations, insertions and inversions) may cause truncation, deletion, inactivation or over-expression of specific genes. We report on a case of OT-DSD associated with an X chromosome inversion. Case report: A 3-month old girl was referred due to atypical genitalia. She was born at term to a 42 years old G3P2A1 mother and her 45 years old unrelated husband with normal weight, length and head circumference. She had normal development, no associated health problems, and family history was unremarkable. Physical examination revealed a 3.1-cm phallus with chordee, scrotal hypospadias, partial penoscrotal inversion and a 0.5 cm3 right gonad palpable in the inguinal region; there were no associated dysmorphic features. At 1.5 months there were normal levels of FSH (3.09 IU/L) and LH (3.67 IU/L), and testosterone (155 ng/dL) was in the normal male range. Ultrasound revealed normal uterus and gonads were in the inguinal regions. Urethra-cystoscopy and vaginoscopy at 9 months revealed a urogenital sinus with high vaginal confluence. Laparoscopy and gonadal biopsies were also performed; the left gonad was an ovotestis with multiple ovarian follicles, while the right gonad was a testis. In both gonads the seminiferous tubules had only Sertoli cells. Karyotype revealed a pericentric X chromosome inversion, 46,X,inv(X)(p22.1q26)dn[20]. FISH on peripheral blood and cultured cells from the right gonad with probes for X (DXZ1) and Y (DYZ3) centromeres and SRY (Yp11.3 - 122 Kb) showed only two X chromosome signals. Array GH analysis (Cytoscan 750K, Affymetrix) showed a 1.3 Mb deletion distal to the short arm breakpoint (Xp22.31), which was reported as VOUS, and a 9 Mb region of LOH on chromosome 9. Discussion: Several cases of X pericentric inversion with different breakpoints have been reported; though phenotypes of female heterozygotes are often normal, early menopause, irregular menses, gonadal dysgenesis or sterility have been described. In this case, it is plausible that the genomic rearrangement could have affected long-range regulation of SOX3 (located in Xq27.1) resulting in ectopic expression of this gene in the bipotential gonad. In addition, the features detected in array GH may have a role in the phenotype. Different methods to determine the exact chromosomal breakpoints and copy number variations in this region will be required.

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Cytogenetic and molecular characterization of an SRY-negative 46, XX ovotesticular DSD

Revista de Ciências Médicas e Biológicas ◽

10.9771/cmbio.v20i2.44045 ◽

2021 ◽

Vol 20 (2) ◽

pp. 341-343

Author(s):

Natalia Dayane Moura Carvalho ◽

Tirciana Carvalho Passos ◽

Vania Mesquita Gadelha Prazeres ◽

Cleiton Fantin

Keyword(s):

Ovarian Tissue ◽

Bilateral Mastectomy ◽

Total Testosterone ◽

Disorder Of Sex Development ◽

Molecular Analyses ◽

Sex Development ◽

Negative Case ◽

Sexual Determination ◽

Genital Ambiguity ◽

Male Sex

Introduction: Ovotesticular disorder of sex development is a rare condition by the concomitant presence of testicular and ovarian tissue, and usually presents genital ambiguity. Are chromosomally heterogeneous, and cytogenetic analyses is relevant. Objective: report on a patient from Manaus, Amazonas state with ovotesticular disorder of sex differentiation 46, XX and SRY-negative. Case report: Patient of 19 years, first child of non-consanguineous parents. At birth, the patient was diagnosed with genital ambiguity and, without early diagnosis, he was registered as being of the male sex. The patient underwent surgery to correct bilateral cryptorchidism, orchiopexy and colpectomy. During puberty, he developed female and male sexual characteristics. Endocrinological (normal total testosterone and estradiol as high follicle-stimulating hormone and luteinizing hormone), histopathological (right gonad, ovarian follicles and left gonads, atrophic testicles), karyotype (46, XX) and molecular (SRY-negative). Diagnosis of ovotesticular disorder of sex development was established. The patient chose to remain male and underwent bilateral mastectomy, vaginal colpectomy and bilateral gonadectomy. Currently, the patient receives hormonal replacement therapy, follow-up with a multi-professional approach and awaits masculinizing genitoplasty. Discussion: In diagnostic research, cytogenetic and molecular analysis are primary tools. For OT-DSD individuals with 46, XX, the female sex is suggested as the best sex option. Unlike the reported cases, the patient chose the male sex, since the sex at registration of birth was important in his choice. Conclusion: Cytogenetic and molecular analyses allowed us to assist in the etiological diagnosis of the patient with OT-DSD from Manaus. However, molecular analyses are necessary to elucidate the genes involved in the sexual determination of this patient.

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Cytogenetic and molecular diagnosis of Fanconi anemia revealed two hidden phenotypes: Disorder of sex development and cerebro‐oculo‐facio‐skeletal syndrome

Molecular Genetics & Genomic Medicine ◽

10.1002/mgg3.694 ◽

2019 ◽

Vol 7 (7) ◽

Author(s):

Abir Ben Haj Ali ◽

Ahlem Amouri ◽

Marwa Sayeb ◽

Saloua Makni ◽

Wajih Hammami ◽

...

Keyword(s):

Molecular Diagnosis ◽

Fanconi Anemia ◽

Disorder Of Sex Development ◽

Sex Development

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Society for Endocrinology UK Guidance On The Initial Evaluation Of A Suspected Difference or Disorder Of Sex Development (DSD) (Revised 2021)

Clinical Endocrinology ◽

10.1111/cen.14528 ◽

2021 ◽

Author(s):

SF Ahmed ◽

JC Achermann ◽

J Alderson ◽

NS Crouch ◽

S Elford ◽

...

Keyword(s):

Initial Evaluation ◽

Disorder Of Sex Development ◽

Sex Development

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Cytogenetics and sex determination in man and mammals

Journal of Biosocial Science ◽

10.1017/s0021932000023427 ◽

1970 ◽

Vol 2 (S2) ◽

pp. 7-30 ◽

Cited By ~ 26

Author(s):

C. E. Ford

Keyword(s):

Y Chromosome ◽

External Genitalia ◽

Mutant Gene ◽

Normal Female ◽

Human Female ◽

Present Evidence ◽

Male Development ◽

Sex Development ◽

Internal Genitalia ◽

Male External Genitalia

SummarySex in man and probably throughout the class mammalia is normally determined by the presence of a Y chromosome (male) or its absence (female). The presence of genetic loci on both the long and the short arm of the X chromosome in double dose appears to be essential for the development of mature functional ovaries in the human female though a single X suffices in the female mouse.The development of masculine genital anatomy and phenotype is a consequence of prior formation of testes. In the absence of gonads of either kind, female internal and external genitalia are formed but secondary sex development fails. In rare human families a mutant gene suppresses the development of male external genitalia in 46, XY embryos but permits the development of testes and male internal genitalia. The external phenotype is normal female (syndrome of testicular feminization). A sex-linked mutant gene in the mouse has a similar effect.The locus or loci directly concerned with male development might lie wholly on the Y chromosome or might be located on another chromosome or chromosomes. In the latter case it (or they) must be repressed in the female and normally activated by a locus or loci on the Y chromosome in the male. Present evidence does not permit the exclusion of either possibility.

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