A Case of Chromosomal Disorders of Sex Development with Transverse Testicular Ectopia Mimicking Mixed Gonadal Dysgenesis

In this study, we present 3 cases of Down syndrome (DS) associated with disorders/differences of sex development (DSD) and review the literature on this topic. Case 1: 1-year-old child with male genitalia and DS phenotype, 47,XX,+21 karyotype and testicular DSD. Case 2: 11-month-old child with male genitalia and few DS dysmorphisms, 45,X/47,XY,+21 karyotype, and mixed gonadal dysgenesis. Case 3: 4-month-old child with female genitalia and DS phenotype, 47,XY,+21 karyotype and XY complete gonadal dysgenesis. In the literature, among 188 patients, 107 (57%) had Klinefelter syndrome and 61 (33%) Turner syndrome, 12 (6%) had mixed gonadal dysgenesis, 2 (1%) had partial androgen insensitivity, 2 (1%) ovotesticular DSD, and the others had congenital adrenal hyperplasia, XY partial gonadal dysgenesis, XY complete gonadal dysgenesis, and complete androgen insensitivity (1 case each). A typical DS phenotype was found in all individuals of the revision, with the exception of one case, but DSD features were not always reported. In conclusion, the association of DS with sex chromosome DSD is the most frequently observed, whereas associations with 46,XX and 46,XY DSD is extremely rare.

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Transverse testicular ectopia with disorders of sex development

Indian Journal of Urology ◽

10.4103/0970-1591.94965 ◽

2012 ◽

Vol 28 (1) ◽

pp. 92 ◽

Cited By ~ 3

Author(s):

Katsuya Aoki ◽

Kiyohide Fujimoto ◽

Masaomi Kuwada ◽

Yoshihiko Hirao

Keyword(s):

Disorders Of Sex Development ◽

Transverse Testicular Ectopia ◽

Sex Development ◽

Testicular Ectopia

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Functional analysis of novel desert hedgehog gene variants improves the clinical interpretation of genomic data and provides a more accurate diagnosis for patients with 46,XY differences of sex development

Journal of Medical Genetics ◽

10.1136/jmedgenet-2018-105893 ◽

2019 ◽

Vol 56 (7) ◽

pp. 434-443 ◽

Cited By ~ 3

Author(s):

Katie Ayers ◽

Jocelyn van den Bergen ◽

Gorjana Robevska ◽

Nurin Listyasari ◽

Jamal Raza ◽

...

Keyword(s):

Gonadal Dysgenesis ◽

Disorders Of Sex Development ◽

Culture Method ◽

Significant Loss ◽

Subcellular Localisation ◽

Gene Variants ◽

Gene Variant ◽

Clinical Interpretation ◽

Sex Development ◽

Desert Hedgehog

BackgroundDesert hedgehog (DHH) gene variants are known to cause 46,XY differences/disorders of sex development (DSD). We have identified six patients with 46,XY DSD with seven novel DHH gene variants. Many of these variants were classified as variants of uncertain significance due to their heterozygosity or associated milder phenotype. To assess variant pathogenicity and to refine the spectrum of DSDs associated with this gene, we have carried out the first reported functional testing of DHH gene variant activity.MethodsA cell co-culture method was used to assess DHH variant induction of Hedgehog signalling in cultured Leydig cells. Protein expression and subcellular localisation were also assessed for DHH variants using western blot and immunofluorescence.ResultsOur co-culture method provided a robust read-out of DHH gene variant activity, which correlated closely with patient phenotype severity. While biallelic DHH variants from patients with gonadal dysgenesis showed significant loss of activity, variants found as heterozygous in patients with milder phenotypes had no loss of activity when tested with a wild type allele. Taking these functional results into account improved clinical interpretation.ConclusionOur findings suggest heterozygous DHH gene variants are unlikely to cause DSD, reaffirming that DHH is an autosomal recessive cause of 46,XY gonadal dysgenesis. Functional characterisation of novel DHH variants improves variant interpretation, leading to greater confidence in patient reporting and clinical management.

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Analysis of the Wilms' Tumor Suppressor Gene (WT1) in Patients 46,XY Disorders of Sex Development

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2010-2804 ◽

2011 ◽

Vol 96 (7) ◽

pp. E1131-E1136 ◽

Cited By ~ 32

Author(s):

B. Köhler ◽

H. Biebermann ◽

V. Friedsam ◽

J. Gellermann ◽

R. F. Maier ◽

...

Keyword(s):

Kidney Disease ◽

Tumor Suppressor ◽

Tumor Suppressor Gene ◽

Gonadal Dysgenesis ◽

Kidney Development ◽

Wilms Tumor ◽

Disorders Of Sex Development ◽

Suppressor Gene ◽

Sex Development ◽

Cryptorchid Testis

Abstract Context: The Wilms' tumor suppressor gene (WT1) is one of the major regulators of early gonadal and kidney development. WT1 mutations have been identified in 46,XY disorders of sex development (DSD) with associated kidney disease and in few isolated forms of 46,XY DSD. Objective: The objective of the study was the evaluation of WT1 mutations in different phenotypes of isolated 46,XY DSD and clinical consequences. Design: The design of the study was: 1) sequencing of the WT1 gene in 210 patients with 46,XY DSD from the German DSD network, consisting of 150 males with severe hypospadias (70 without cryptorchidism, 80 with at least one cryptorchid testis), 10 males with vanishing testes syndrome, and 50 raised females with partial to complete 46,XY gonadal dysgenesis; and 2) genotype-phenotype correlation of our and all published patients with 46,XY DSD and WT1 mutations. Results: We have detected WT1 mutations in six of 80 patients with severe hypospadias (7.5%) and at least one cryptorchid testis and in one of 10 patients with vanishing testes syndrome (10%). All patients except one developed Wilms' tumor and/or nephropathy in childhood or adolescence. Conclusion: WT1 analysis should be performed in newborns with complex hypospadias with at least one cryptorchid testis and in isolated 46,XY partial to complete gonadal dysgenesis. Kidney disease might not develop until later life in these cases. WT1 analysis is mandatory in all 46,XY DSD with associated kidney disease. WT1 analysis is not indicated in newborns with isolated hypospadias without cryptorchidism. Patients with WT1 mutations should be followed up closely because the risk of developing a Wilms' tumor, nephropathy, and/or gonadal tumor is very high.

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SRY mutation analysis by next generation (deep) sequencing in a cohort of chromosomal Disorders of Sex Development (DSD) patients with a mosaic karyotype

BMC Medical Genetics ◽

10.1186/1471-2350-13-108 ◽

2012 ◽

Vol 13 (1) ◽

Cited By ~ 10

Author(s):

Remko Hersmus ◽

Hans Stoop ◽

Erin Turbitt ◽

J Wolter Oosterhuis ◽

Stenvert LS Drop ◽

...

Keyword(s):

Mutation Analysis ◽

Deep Sequencing ◽

Disorders Of Sex Development ◽

Next Generation ◽

Chromosomal Disorders ◽

Sex Development ◽

Mosaic Karyotype

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Consultation Liaison Psychiatry on Case Management of Children with Mixed Gonadal Dysgenesis Mosaicism 45X (60%) and 46XY (40%)

Health Notions ◽

10.33846/hn50206 ◽

2021 ◽

Vol 5 (2) ◽

pp. 62-66

Author(s):

Jeffriey Agung ◽

Yunias Setiawati

Keyword(s):

Quality Of Life ◽

Gender Identity ◽

Gonadal Dysgenesis ◽

Case Reports ◽

Disorder Of Sex Development ◽

Mixed Gonadal Dysgenesis ◽

Sex Development ◽

Psychological Stressors

There is an increasing in admitted patients with cases of gender identity disorder in the daycare clinic of the Child and Adolescent Psychiatry Division Dr. Soetomo, it is necessary to increase understanding and clinical ability in relation to gender identity disorders through psychiatry consultation discussion, so that management can be achieved properly and comprehensively. Disorder of sex development (DSD) is a medical disorder that is associated with an incompatibility between chromosomes, gonads, phenotypes and anatomy which is characterized by the development of external genital organs that are incompatible with whether it is male or female. Genetalia ambiguos can cause significant psychological stressors for patients or their families, where as a result of the conditions experienced, it will lead to gender dysphoria with the resulting effects, among others, in the form of anxiety, depression and low self-esteem, to affect the quality of life of children as adolescents and adults. . The method of preparing this report is a case analysis and the role of CLP which is given based on the results of the examination and references to management in the field of psychiatry of children and adolescents in cases of DSD from children aged 12 years. Conducted to strengthen the adaptation of patients to problems identifying gender development and to their families by emphasizing the importance of achieving optimal quality of life for children. The results of the case reports describe the role of Consultation Liason Psychiatry through communication and consultation between related areas of expertise, supportive psychotherapy and continuous Cognitive Behavior Therapy (CBT) techniques along with psychoeducation in families providing good development results with results in reducing patient anxiety and depression, based on children's scoring Depression Inventory (CDI) of patients with Mosaicism, Mixed Gonadal Dysgenesis (MGD). The conclusion of this case report is that the problem of psychological stressors that arise in DSD requires psychiatric assistance according to the stages of child development. The important role of psychiatrists in the management of DSD cases has been recognized and stated in the joint consensus for the treatment of individuals with DSD since 2006. CLP needs to be built because of the complexity of treatment and therapy in DSD cases, which involve subspecialty pediatric endocrinology, urology, psychiatry, gynecology, genetics, workers. social nurse and medical ethics. described in the algorithm below in the management of cases of gender dysphoric. Keywords: disorder of sex development; mixed gonadal dysgenesis; consulation liason psychiatry disorder of sex development; mixed gonadal dysgenesis; consulation liason psychiatry

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46 XY DISORDER

The Professional Medical Journal ◽

10.29309/tpmj/2016.23.10.1723 ◽

2016 ◽

Vol 23 (10) ◽

pp. 1202-1208

Author(s):

Muhammad Naveed Najeeb ◽

Sadiq Hussain Malik ◽

Sheikh Khurram Salam Sehgal ◽

Ameer Ahmad Malik ◽

Saqib Mehmood

Keyword(s):

Physical Examination ◽

Study Design ◽

Gonadal Dysgenesis ◽

Disorders Of Sex Development ◽

Serum Testosterone ◽

Androgen Insensitivity Syndrome ◽

Base Line ◽

Reductase Deficiency ◽

Androgen Synthesis ◽

Sex Development

Objectives: The Disorders of Sex Development are classified as 46, XY DSD,46, XX DSD and Chromosomal DSD according to the chromosomal constitution of the affectedpersons. 46, XY DSD is further classified into Androgen Synthetic Defect, Androgen InsensitivitySyndrome Gonadal Dysgenesis, 5-Alpha Reductase Deficiency, Persistent Mullerian DuctSyndrome and Isolated Hypospadias according to the pathophysiology of the disease. Theaim of present study was to classify 46, XY patients into their subclasses on the basis of theirhormonal profile and physical examination. Study Design: Observational descriptive study.Setting: Biochemistry Department University of Health Sciences for Karyotyping and Geneticassessment, and its allied institution Biochemistry Department Quaid-e-Azam Medical CollegeBahawalpur for hormonal analysis, along with Pediatric Medicine Departments of Quaid-e-AzamMedical College / Bahawal Victoria Hospital Bahawalpur for collection of Sample and clinicalassessments. Period: June 2015 to December 2015. Study Design: Observational descriptivestudy. Material and Methods: 53 patients with 46, XY DSD were recruited. Complete clinicalhistory and data of each patient was recorded in the research proforma. Genitals examinedfor the phallus length and size, position of urinary meatus, palpation of gonads and shape ofthe labioscrotal folds. Ultrasonography examination of each patient was performed to look forundescended testes and for the presence of either male or female internal reproductive organs.Results: Base line levels of serum Testosterone Dihydrotestosterone Luteinizing hormone,Follicle stimulating hormone, 17-OH-Progesteron and Anti-mullerian hormones were measuredby ELISA technique. Testosterone and DHT were measured again after hCG stimulation. Onthe basis of physical examination, ultrasonographic findings and hormonal profile diagnosisof the types of 46, XY DSD was possible in 27 (51%) of patients. Androgen synthesis defect asa cause of 46, XY DSD was diagnosed in 7(13%) patients, Androgen insensitivity syndrome in6(11%) patients, 5-Alpha reductase deficiency in 3(6%) patients, Gonadal Dysgenesis in 3 (6%),Persistent Mullerian Duct Syndrome in 3(6%) and Isolated Hypospadias in 2 (4%) patients.There were 26 (49%) patients which remain undiagnosed with the algorithm of diagnosis usedin the present study.

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